Life Sciences Commons^™

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 …

Optimization Of Growth Conditions And Characterization Of Properties On Christensenella Minuta, Qing Ai

Wayne State University Theses

Currently, increasing numbers of people are suffering from obesity. The gut microbiome becomes a useful approach to control the mechanisms associated with obesity. A novel bacterium, Christensenella minuta, which was discovered in 2012, triggers body weight loss. Our purpose in this study is to further realize characteristics of C. Minuta as a potential probiotic supplement for future obesity studies. This study determines the following characteristics of C. Minuta: DNA identification, turbidity verification, generation time, as well as optimization of pH and temperature. To test the tolerance of C. Minuta as a gastrointestinal treatment, the pH and bile salts concentration in …

An Evaluation Of Endocrine Disrupting Effects Of Emerging Contaminants Using Daphnia Pulex And Danio Rerio, Lakshmi Neha Reddy Alla

Wayne State University Theses

The limit of the availability of water is based on two factors, scarcity and quality. Conserving and protecting our water resources one of the most critical issues facing humanity as we struggle to deal with contaminated lakes and rivers and climate change. The main aim of this study is to examine toxicity of known water contaminants on aquatic model organisms and be able to develop methodology that will enable the characterization of endocrine disrupting potential of water samples with unknown contaminants. Both the category of water contaminants known as pharmaceuticals, personal care products that are known as PPCPs and other …

Metformin, Glucotoxicity And Islet Dysfunction, Sartaj S. Baidwan

Wayne State University Theses

METFROMIN, GLUCOTOXICITY AND ISLET DYSFUNCTION

by

SARTAJ BAIDWAN

MAY 2017

Advisor: Dr. Anjaneyulu Kowluru

Major: Pharmaceutical Sciences

Degree: Master of Science

Glucotoxicity is the leading cause for β-cell dysfunction [e.g., defective glucose-stimulated insulin secretion] in Type 2 Diabetes [T2DM]. Recent studies from our lab have shown sustained Rac1 activation leading to the activation of downstream signaling steps including stress kinase [p53, p38MAPK] activation and mitochondrial dysregulation [caspase-3 activation] in pancreatic islet beta-cells exposed to glucotoxic [HG] conditions [20 mM; 24 hrs]. Metformin [MF] is an oral anti-diabetic drug that is being widely prescribed to T2DM. MF works by suppressing hepatic …

The Effect Of Acetylation Of Cytochrome C On Its Functions In Prostate Cancer, Viktoriia Bazylianska

Wayne State University Theses

Prostate cancer is the second leading cause of cancer death among men in America. The progression of cancer goes along with the Warburg effect, a metabolic switch from depending primarily on mitochondrial respiration to glycolysis. In addition, cancer cells manage to evade apoptosis. Cell signaling, via posttranslational modifications (PTMs), is one of the most important means of regulation, and most commonly dysregulated in cancer. In prostate cancer, androgen signaling plays a crucial role in driving cell proliferation.

Mammalian Cytochrome c (Cytc) is a multifunctional protein involved in cellular life and death decision. It is an essential component of the electron …

Development Of Gi Sustainable Probiotic Beads Using Microencapsulation, Jiarun Cui

Wayne State University Theses

Scientists tend to pay a lot attention to probiotics in recent years, due to its health related benefits for humans. Encapsulation is a necessary way to protect probiotics from being killed by harsh conditions of the gastrointestinal tract, and to help probiotics to release in the intestinal environment. This study is mainly focusing on the encapsulation technique of Christensenella minuta, and the food product development of C. minuta beads. The extrusion technique was applied as the encapsulation method, with alginate as the encapsulation material. The effect of single encapsulation and double encapsulation of C. minuta was compared to determine the …

Optimization Of Growth Conditions Of "Eubacterium Hallii" As A Potential Probiotics, Sampurna Guhathakurta

Wayne State University Theses

ABSTRACT

OPTIMIZATION OF GROWTH CONDITIONS OF “Eubacterium hallii” AS A POTENTIAL PROBIOTICS

by

SAMPURNA GUHATHAKURTA

May 2017

Advisor: Dr. Kequan Zhou

Major: Nutrition and Food Science

Degree: Master of Science

Probiotics are becoming popular to a greater extent over the past two decades for their potential benefits on human health. Therefore, they are widely used in the food industry by incorporation into food products. Nowadays, there are a lot of probiotics which are famous in the market. In this study, the strain of Eubacterium hallii was used because it has a significant importance in the pharmaceutical or food industry especially …

Investigation Into Roseburia Intesinalis For Optimal Growth And Survivability Conditions For Potential Probiotic Use, Lisa Rana Felczak

Wayne State University Theses

Obesity and diabetes is an epidemic of increasing concern. Certain novel bacteria have been found to be an aid in reversing some of the mechanisms associated. This study focused on investigating the optimal stability conditions for R.intestinalis that can associate with an increase in growth. First, environmental conditions were tested to find the optimal conditions associated with each. Once growth conditions were found, generation time was calculated and various prebiotics were used to investigate a potential for additional growth. Next, common antibiotics were tested to see if the R.intestinalis could still show growth when exposed. Large batches of R.intestinalis were …

The Potential Stimulation Of C. Minuta Growth By Various Prebiotics, And Its Sensitivity To Various Antibiotics, Maria Elena Hakim

Wayne State University Theses

Gut microbiota play a crucial role in maintaining intestinal health and integrity; a feature that is both heritable, as well as affected by the environment and lifestyle. Probiotics are supplements containing live microorganisms that act in a similar manner to gut microflora, and maintain a balance in the latter. C. minuta is a novel bacterium in the gut that was found to be associated with reduction in body weight and adiposity. The aim of this study was to determine the possible effects of different prebiotics on C. minuta growth, and the survival of C. minuta in response to different antibiotics. …

Fam129b, A Novel Adherent Junction Protein, Forms A Complex With Keap1, Fatme Ali Hachem

Wayne State University Theses

FAM129B/Minerva, a protein implicated in melanoma cell invasion, has been shown to suppress TNFα induced apoptosis in cancer cells (Song, Evans & Evans (2010), JBC 286, 10201-09), thus contributing to the survival of metastatic cells. KEAP1, a substrate recognition molecule for the CUL3 E3 ubiquitin ligase, plays a central role in the activation of the TNFα pathway. We wish to test the hypothesis that the up-regulation of FAM129B in cancer cells suppresses apoptosis by sequestering KEAP1, thus preventing its participation in the apoptotic pathway. The first step is to demonstrate that FAM129B and KEAP1 form a complex. We have cloned …

Development Of Student Data Visualization Tool, Adaption Of Clostridium Difficile Toxin A Into Protein Delivery Vehicle, And Elucidation Of Tcdc Mechanism Of Toxin Control, Adam Boyden

Wayne State University Theses

Advancing student success in higher education is of paramount importance, and is in need for a tool that visualizes student data in a longitudinal manner. Student Circos plots achieve this by plotting student data in circular plots, depicting the timeline and grades for students selected by demographic or performance information. Cellular delivery of exogenous proteins is a bountiful area of research. However, most current systems have limited in vivo applications and most lack cellular specificity. By adapting Toxin A from Clostridium difficile, the goal was to create a cell specific protein delivery vehicle that would be robust in vivo. However, …

Effects Of Palm Oil Tocotrienols Rich Fraction On Cholesterol Efflux, Erandi Jayamini Jayawardana Arachchige

Wayne State University Theses

Tocotrienols are naturally occurring bioactive compounds which possess beneficial effects on multiple chronic diseases including atherosclerosis and cancer. It is believed to exert atheroprotective effects via promoting reverse cholesterol transport, a process that removes excess cholesterol from the body. Cholesterol efflux is an early step in reverse cholesterol transport and impaired cholesterol efflux is known to trigger foam cell formation, a hallmark of atherosclerosis. An increase in cholesterol efflux and decrease in cholesterol influx in macrophages has been suggested to reduce atherosclerosis risk by reducing foam cell formation. In addition, tocotrienols have shown anti-cancer effects on Non-small cell lung cancer …

Endocrine-Disrupting Properties Of Pharmaceuticals And Personal Care Products (Ppcps): An Evaluation Using Aquatic Model Organisms, Manahil Monshi

Wayne State University Theses

Thousands of chemicals have introduced into the environment as a result of human activity since the industrial revolution, and the U.S. Government Accountability Office has estimated that as many as 1,500 new chemical entities are synthesized each year ("Key Issues: Toxic Chemicals - High Risk Issue," 2017). Many of these chemicals are now found in surface water and ground water and can have detrimental effects on environmental health and on human health. This anthropogenic contamination has resulted in the labeling of the diverse array of chemicals found in water, which are not routinely monitored or regulated, as contaminants of emerging …

Determination Of The Direct Protein-Protein Interactions In The Drosophila Sin3a Complex, Ian Moore

Wayne State University Theses

The proteins that comprise the Drosophila SIN3 220 and SIN3 187 complexes are currently known. Limited information with regard to interacting complex member proteins has been described. Much of these data are results of high-throughput investigations, and there have been no studies done to reconstitute all direct interactions within the complex. The unique C-terminal region of the SIN3 220 isoform was used to test for interactions with other complex proteins using the bacterial expression system. Additionally, the region of Caf1-55 necessary for interaction with SIN3 in vivo was identified using a truncation mutant. The results of this work identified novel …

Mechanistic And Inhibitory Analysis Of Clostridium Difficile Associated Diseases, Brianna Marie Jackman

Wayne State University Theses

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The Effect Of Oil Palm Phenolics (Opp) And Curcumin On Plasma Metabolomic Profile In Atherogenic Diet Induced Rat Model Of Alzheimer’S Disease (Ad), Soniya Katekar

Wayne State University Theses

Alzheimer's disease (AD) is the most widely recognized reason for dementia in the aging population. It is described by intellectual decay and deposition of ß-amyloid plaques in the hippocampus. It has been demonstrated that hypercholesterolemia incited by elevated cholesterol abstain from food is related with AD advancement. Expanded level of oxidative stress has additionally been seen in AD patients. An essential methodology to treat or postpone the disability depends on dietary change, utilizing nourishment supplements. OPP, a water-soluble fraction from oil palm fruit, rich in phenolics has been found to possess significant antioxidant activities. Curcumin, a polyphenol extricated from the …

Protein Phosphatase 2a Function And Regulation In Insulin Resistant Human Skeletal Muscle Cells, Shukurat Sulaiman

Wayne State University Theses

Protein Phosphatase 2A (PP2A), a major serine/threonine phosphatase involved in insulin signaling pathway, plays a critical role in the development of insulin resistance and type 2 diabetes (T2D), which is characterized with hyperinsulinemic hyperglycemic condition. Moreover, majority of the glucose disposal takes place in the skeletal muscle which is also the main tissue responsible for insulin resistance. The catalytic subunit of PP2A (PP2Ac) can interact with multiple regulatory subunits and other regulatory proteins as well as substrates. These interactions are important for maintain normal PP2A function and subsequent cell signaling. We hypothesized that hyperinsulinemic hyperglycemic condition and insulin stimulation would …

Synaptotagmin C2b Ca2+-Binding Loops Impose Distinct Exocytosis Phenotypes, Michael W. Schmidtke

Wayne State University Theses

Regulated exocytosis from chromaffin cells in the adrenal medulla plays a critical role in maintaining organismal homeostasis. In the absence of stress, these cells release physiologically relevant substances into the blood stream only in limited quantities, whereas stressful conditions result in a rapid deluge of signaling molecules used, for example, to increase heart rate and pain tolerance. Although the cellular mechanisms governing the switch from low-level to stress-induced secretion are not well understood, recent evidence has implicated the exocytotic Ca2+-sensing protein Synaptotagmin (Syt) in this role.

Two isoforms of Syt are expressed in chromaffin cells (Syt-1 and Syt-7), and each …

Elucidating Structure, Function, And Small Molecular Interactions Of Human Immunodeficiency Virus And Chikungunya Virus, Kristin Nicole Slater

Wayne State University Theses

Abstract HIV-1:

Human immunodeficiency virus-1 (HIV-1) is a widespread, incurable retrovirus known to cause

immunodeficiency and a shortened life span. Despite successful treatment methods, HIV-1

frequently mutates, resulting in antiviral resistance. Many therapies target the HIV-1 protease

(PR), which is responsible for cleaving the viral polyprotein essential for its life cycle. HIV-1 PR

often evades treatment by way of mutations and less commonly through residue insertions. We

have identified a clinical isolate with a five residue insertion between residues 28 and 29.

Through molecular dynamics simulations we analyzed the protease protein structure and

determined that the residue insertion created a …

Redox Responsive Cerium Oxide Nanoparticles And Cd44 Targeted Nanomicelles For Selective Cancer Therapy, Zhaoxian Wang

Wayne State University Theses

Redox-responsive cerium oxide nanoparticles (CNPs) can play a versatile role in cancer therapy due to their ability to induce oxidative stress under proper pH conditions. Hyaluronic acid micelles with a high affinity to CD44 receptor which achieved more cytotoxicity towards cancer cells. The polymer-coated CNPs and HA-SMA-TPGS-CDF nanomicelles were developed for cancer therapy. The results showed that the toxicity of CNPs in tumor cells was mediated by the pro-oxidant property of CNPs under relative low pH conditions (pH~6.5) of the tumor microenvironment whereas CNPs play a (cytoprotective) anti-oxidant role, scavenging reactive oxygen species and reducing oxidative stress under normal pH …

Expression, Purification And Characterization Of Lysine Methyltransferase Smyd5, Wen Xue

Wayne State University Theses

Methylation of histones and non-histone proteins play vital roles in numerous cellular processes including gene expression regulation and DNA damage response. The identifications of methyltransferase SMYD protein family are not well characterized. SMYD5 is a unique and critical member of SMYD family involved in immune response, stem cell renew, hematopoiesis regulation and cancer metastasis. Understanding its function and structure is monumental to human disease. With the achievement of SMYD5 expression and purification, the association between SMYD5 and its substrate histone H4 has been investigated. While possessing a poly-E tail instead of the TPR domain included in other members, SMYD5 is …