Life Sciences Commons^™

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

.

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 …

An Analysis Of Blue Ash (Fraxinus Quadrangulata) Regeneration In Southeastern Michigan In The Presence Of Emerald Ash Borer (Agrilus Planipennis), Benjamin Adam Spei

Wayne State University Theses

Abstract

AN ANALYSIS OF BLUE ASH (FRAXINUS QUADRANGULATA) REGENERATION IN SOUTHEASTERN MICHIGAN IN THE PRESENCE OF EMERALD ASH BORER (AGRILUS PLANIPENNIS)

by

BENJAMIN A. SPEI

May 2016

Advisor: Dr. Daniel M. Kashian

Major: Biological Sciences

Degree: Master of Science

Since the introduction of the invasive bark beetle emerald ash borer (EAB) (Agrilus planipennis Fairmaire) (Coleoptera: Buprestidae) to southeastern Michigan, most native ash species (Fraxinus spp.) such as white ash (F. Americana), black ash (F. nigra), and green ash (F. pensylvanica) have suffered mortality rates exceeding 99% after infestation. This has led to the loss of seed sources resulting in a …

Design And Synthesis Of Enzalutamide-Isothiocyanate Hybrid Drug As Anti-Prostate Cancer Agent, Siyu Ou

Wayne State University Theses

Isothiocyanate (ITC), such as sulforaphane (SFN), is an active metabolite of dietary glucosinolate from cruciferous vegetables. SFN-rich extracts have been recently tested in recurrent prostate cancer (PCa) patients and notably prolonged PSA doubling time without Grade 3 adverse events. One of the anti-PCa mechanisms of SFN is to inhibit HDAC6, which further triggering androgen receptor (AR) degradation. We have incorporated ITC to the chemical scaffold of enzalutamide (Enz) to create Enz-ITC hybrid molecules with an intention to intracellularly deliver ITC to AR-Hsp90-HDAC6 complex and therefore improving anti-PCa efficacy of both parental drugs. Two Enz-ITCs and one Enz-ITC N-acetyl cysteine (NAC) …

Targeted Delivery Of Nrf2 Sirna Using Modular Polymeric Micellar Nanodelivery System For Efficient Target Gene Knockdown In Hepatocellular Carcinoma, Shaimaa Mohamed Ibrahim Yousef

Wayne State University Theses

Tumor selective drug delivery as well as chemotherapy associated multi drug resistance (MDR) pose tremendous hurdles for effective cancer therapy. In this regard, designing multifunctional nanocarriers loaded with drug/gene payloads and engineered with tumor targeting ligands can serve as a modular platform for targeted drug/gene delivery. In this study we undertook the synthesis of a self-assembling block copolymer constructed using poly(styrene-co-maleic anhydride, partial iso-octyl ester) (SMAPIE) and branched polyethylenimine (PEI) as building blocks and evaluated its micelle forming ability, siRNA complexation and siRNA delivery potentials. In addition, we engineered galactosamine decorated nanomicelles using modular “click” chemistry based approaches for evaluating …

Dendrimer-Coated Iron Oxide Theranostic Nanoparticles For Cancer Imaging And Therapy, Duy Khanh Luong

Wayne State University Theses

The bleak prognosis for patients diagnosed with metastatic cancer along with the low therapeutic efficacy and the recurrence of cancer in conventional chemotherapy are prompting clinical medicine to adopt a new strategy to detect cancer in early stage and to deliver the anticancer drugs specifically to tumor site to enhance therapeutic efficiency and minimize side effects. The aim of this study is to design a theranostic nanocarrier consisting of iron oxide nanoparticles (SPIONs) for magnetic resonance imaging (MRI) and Polyamidoamine dendrimers conjugated with folic acid (FA-PAMAM) for active targeted delivery of a highly potent but extremely lipophilic anticancer compound 3,4-difluorobenzylidene …

Evolutionary Ecotoxicology Of Salinity Tolerance In Daphnia Pulex: Interactive Effects Of Clonal Variation, Salinity Stress, And Predation, Xinwu Liu

Wayne State University Theses

Evolutionary ecotoxicology addresses effects of toxic chemicals in an ecological context and considers the potential evolutionary responses of organisms following exposure to toxins. Despite decades of research, the effects of salinity stress in freshwater systems, partly from road salt pollution, on a keystone species, Daphnia pulex, in its interaction with predators have received very limited attention. In this study, I quantified D. pulex clonal variation in response to salinity stress and the lethal and non-lethal effects of Chaoborus (a dominant planktivore in fishless ponds). Behavioral, morphological, and life history responses of two D. pulex clones, known to differ in salinity …

Development Of A Dreissena Bioassay To Assess The Toxicity Of Contaminants Across Two Life-History Stages, Caroline Joyce Addis

Wayne State University Theses

Dreissenid mussels (Dreissena polymorpha and D. bugensis) have rapidly become widespread and ubiquitous in North America since their introduction into the Great Lakes in the 1980s. The resulting environmental and economic impacts of their invasion have been extensive, negatively affecting biodiversity and costing millions of dollars in control efforts and damage to power generation and water treatment facilities. Although dreissenids are often associated with negative impacts, they may present a practical tool for toxicology studies. The typically sessile behavior of the benthic adults coupled with the planktonic nature of the veligers allow for a more complete evaluation of water quality …

Effects Of Local Muscle Fatigue On Proprioception And Motor Learning, Gowtami Datla

Wayne State University Theses

ABSTRACT

EFFECTS OF LOCAL MUSCLE FATIGUE ON PROPRIOCEPTION

AND MOTOR LEARNING

by

GOWTAMI DATLA

May 2016

Advisor: Dr. Qin Lai

Major: Kinesiology and Exercise Science

Degree: Masters of Education

Background: Muscle fatigue is an exercise induced decline in the ability of muscles to produce force or power. Recent studies showed that decline in proprioception due to fatigue lead to an increasing risk of falls and injury. However, it was unknown whether fatigue-induced proprioception decrease affects skill acquisition and memory consolidation. Purpose: The aim of the study was to investigate the effects of local muscle fatigue on perceptual motor learning in …

Regulators Of Ins-6, A Major Node Of The Insulin-Like Peptide Network For Developmental Plasticity, Lisa Li

Wayne State University Theses

In C. elegans, an insulin-like peptide (ILP) network coordinates various physiological

processes, including developmental plasticity, to enhance survival under different environments. During stressful conditions, such as high temperatures, low food and high population density, first-stage larval worms enter an alternative developmental arrest program called dauer. When ideal environmental conditions are restored, worms exit from the dauer stage to go through reproductive adulthood. Different subsets of ILPs regulate the entry into versus the exit from the dauer state. For example, the ILP ins-6 plays a minor role in inhibiting dauer entry from the ASI sensory neurons, but a more primary role …

A Five Residue Insertion Between Codons 28 And 29 Of The Hiv-1 Protease Gene Reduces The Replicative Capacity Of The Virus, Cathy Mcleod

Wayne State University Theses

HIV-1 protease (PR) is a 99 amino acid protein responsible for cleavage of the viral polyprotein. We have identified a novel clinical isolate, MDR/28, which contains a five residue insertion between codons 28 and 29 of a multi-drug resistant (MDR) PR. This clinical isolate displays reduced viral replicative capacity compared to the wild-type. As opposed to drug-resistance mutations, studies on insertions remain largely underrepresented in the literature, and the consequences of such insertions are largely unknown. To understand the mechanism leading to reduced replicative capacity, three PR models were created and subjected to 40ns molecular dynamics simulations: MDR/28, wild type, …

Histological Evidence Of The Effect Of Oil Palm Phenolics In Atherogenic Diet Induced Rat Model Of Alzheimer’S Disease, Kenechukwu Monplaisir Monplaisir

Wayne State University Theses

BACKGROUND: Alzheimer’s disease (AD) is a neurodegenerative disease with the clinical presentation of memory loss and cognitive impairment. Alzheimer's disease pathology is the accumulation of beta amyloid plaques and neurofibrillary tangles.

METHOD: In this study atherogenic diet was used to induce AD in aged Brown Norway rats. The rats were assigned to the following four groups fed isocaloric diets; control group (C ),high cholesterol diet (H), high cholesterol + oil palm phenolics group (HP), high cholesterol + curcumin group (HC). The impact of oil palm phenolics (OPP) on neuronal health and its effect on amyloid deposition was evaluated using histology …

Contribution Of Cx3cr1/Fractalkine (Cx3cl1) Axis To The Progression Of Non-Small Cell Lung Cancer (Nsclc), Rhonda Prince

Wayne State University Theses

A thesis is presented on the characterization of the contribution of the chemokine axis, CX_3CR1/Fractalkine, to the progression of Non-Small Cell Lung Cancer (NSCLC). Cancer is the second leading cause of death in the United States, and Lung cancer is one of the four leading causes of the disease. Carcinoma cells, unlike their normal counterparts, gain the ability to express chemokine receptors. Understanding if/how this gain of expression contributes to the progression of cancer could provide a lucrative therapeutic target. Goals of the study include investing if the NSCLC cell line A549, an adenocarcinoma cell line, express the chemokine receptor …

Impact Of Cefazolin Co-Administration With Vancomycin To Reduce Development Of Vancomycin Intermediate Staphylococcus Aureus, Nivedita Birbahadur Singh

Wayne State University Theses

IMPACT OF CEFAZOLIN CO-ADMINISTRATION WITH VANCOMYCIN TO REDUCE DEVELOPMENT OF VANCOMYCIN INTERMEDIATE STAPHYLOCOCCUS AUREUS

by

NIVEDITA B SINGH

August 2106

Advisor: Dr. Michael J. Rybak

Major: Pharmaceutical sciences

Degree: Masters of Science

Objective: Development of resistance in S. aureus has been a big concern in the treatment of infections caused by the organism. The line of therapy used today has a disadvantage of slowly developing cross-resistance for antibiotics such as DAP secondary to prior VAN exposure. Therefore, alternative therapy is needed to prevent the emergence of VAN resistance and cross-resistance to other antibiotics. The primary aim of this experiment is …

Functional Characterization Of The Novel Prdm Gene Apox In Tribolium Castaneum, Xin Wang

Wayne State University Theses

Previous work revealed that embryonic and post-embryonic knockdown (KD) of Tribolium Prdm gene Apoptix (Apox) leads to phenotypes, such as melanotic spots in external tissue of larval and pupal body. One part of my research is screening for Apox-specific phenotypes by RNA interference with a second Apox dsRNA. My results revealed that Apox is essential for the embryonic and post-embryonic survival and plays an important role in the regulation of embryonic and post-embryonic development in Tribolium, such as bristle formation. In addition, previous work showed that phenotypes of Apox KD Tribolium were significantly rescued by combinatorial knockdown of Apox and …

In Vitro Gastrointestinal Digestion Model To Monitor The Antioxidant Properties And Bioaccessbility Of Phenolic Extracts From Elderberry (Sambucus Nigra L.), Ninghui Zhou

Wayne State University Theses

This study performed an in vitro gastrointestinal digestion model to monitor the antioxidant properties of phenolic extracts derived from the elderberry (Sambucus nigra L.). The stability and antioxidant qualities of phenolic compounds from elderberry were assessed by an in vitro gastrointestinal digestion model involving pepsin digestion (to simulate gastric digestion) and pancreatin digestion (to simulate small i22ntestine conditions). Digested and undigested elderberry were subject to antioxidant assays including total phenolic content (TPC) assay, DPPH radical scavenging assay, and oxygen radical absorbance capacity (ORAC) assay. Our result showed that digestion process significantly reduced DPPH radical scavenging activity but had no significant …

Structure Function Studies Of Hiv-1 Protease, Bradley James Keusch

Wayne State University Theses

HIV-1 is the causative agent of the devastating human disease Acquired Immunodeficiency Syndome (AIDS). While much progress has been made over the past two decades, HIV-1 remains a major global health concern. HIV-1 protease is 99-amino acid homodimer aspartyl protease that is essential to the life cycle of HIV. This has rendered it an attractive and very successful drug target. However, due to the high error rate of the HIV -1 reverse transcriptase, drug resistance mutations in the protease can develop very rapidly in some patients, rendering current protease inhibitors (one of the main classes of drug in common antiretroviral …

Relationships Of Dietary Protein And Phosphorus With Protein Energy Wasting In Hemodialysis Patients, Dina Angela Tallman

Wayne State University Theses

Both higher dietary phosphorus intake and a greater dietary phosphorus to protein ratio are associated with increased death risk in hemodialysis (HD) patients even after adjustments for serum phosphorus, type of phosphate binder used, and dietary protein, energy, and potassium intake. Furthermore, dietary phosphorus restriction to control serum phosphorus is often associated with a reduction in protein intake, which is associated with muscle wasting and poor survival. One highly prevalent complication of end stage renal disease is protein energy wasting (PEW), a state of decreased body protein and fat mass, which is strongly associated with increased morbidity and mortality in …

The Role Of E3 Ligase Parkin In Trafficking Of Monoamine Storage Vesicles In Rat Model Of Methamphetamine Neurotoxicity, Heli Dineshchandra Chauhan

Wayne State University Theses

Methamphetamine (METH), a psychostimulant, is a widely used drug of abuse. METH is toxic to dopaminergic (DAergic) and serotonergic (5-HT) nerve terminals in the striatum when administered at high doses. METH releases Dopamine (DA) from vesicular monoamine transporter 2 (VMAT2) containing synaptic vesicles and induces oxidative stress by auto-oxidation of DA. The VMAT2 plays a neurprotective role by sequestering cytoplasmic DA into vesicles for storage and protection from auto-oxidation. It has previously been shown that METH toxicity is associated with impaired VMAT2 trafficking and oxidative damage to the E3 ligase parkin. CDCrel1, a protein found to inhibit exocytosis, is regulated …