Digital Commons Network^™

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 …

Novel Protein Phosphatase 2a Complexes In Skeletal Muscle From Obese Insulin Resistant Human Participants, Divyasri Damacharla

Wayne State University Theses

Type 2 Diabetes is a metabolic disorder associated with insulin resistance and consequent high blood glucose levels. Maximum glucose disposal takes place in skeletal muscle and studying skeletal muscle insulin resistance is crucial. Protein Phosphatase 2A (PP2A) is one of the major serine/threonine phosphatases belonging to PhosphoProteinPhosphatase (PPP) family. It constitutes about 80% of all serine/threonine phosphatases. It is regulated by numerous regulatory subunits as well as other substrate molecules and post translational modifications. This alters their localization, activity and also its target molecules. Many evidences show the effect of insulin on PP2Ac and its abnormal regulation in conditions of …

Desensitization Of Hacat Keratinocytes To Vitamin D3 Occurs Via Loss Of Redd1 Regulation Of The Mtor Pathway, Michelle Leigh Jones

Wayne State University Theses

Vitamin D3 treatment has long been considered in the treatment of cancer due to its well-documented anti-proliferative effects in vitro. While clinical studies have been positive in other cancers, results are inconclusive in cases of basal cell carcinoma. To better understand the reasons underlying this disconnect, this study employs an immortalized human keratinocyte cell line (HaCaT) to observe the effects of vitamin D3 treatment on cellular proliferation. The results show that both activate vitamin D3 (calcitriol) and its precursor (cholecalciferol) increase proliferation of these cells. Real-time PCR and western blot data indicate that the mTOR pathway becomes activated despite increased …

Similarities And Differences Between Heterosexual And Homosexual Couples Based On Marq Data, Kraig S. Shattuck

Wayne State University Theses

There has been a lack of comparative research on homosexual couples, comparing them to heterosexual couples, which is also grounded in solid theory. In order to remedy this, evolutionary theory is used to make predictions on similarities and differences between heterosexual and homosexual couples within three domains, relationship satisfaction, jealousy, and mate guarding. It was predicted that 1) homosexual couples would not differ from heterosexual couples in relationship satisfaction; 2) some gender differences relating to jealousy would be the same and some would be reversed in homosexual individuals; 3) mate guarding would be present, but lower, in homosexual individuals as …

Detection Of Beneficial Microbiota In Mouse Colon, Aranya Linpisanl

Wayne State University Theses

Lactic acid bacteria (LAB) and Bifidobacterium are the most common types of microbes used as probiotics. They are present in the human gastrointestinal tract and have a significant influence on our health and well-being. Microbiota plays an important role in host metabolism and provides a natural defense mechanism against invading pathogens. This experiment was focusing on establish a method to detect the gastrointestinal tract microbiota, either by fecal or colonic tissue DNA extraction.

The experiment comparing 2 types of DNA extraction; ZR Fecal kit and DNAzol direct. DNAzol direct was easy to use but was not suitable for long term …

Delta-Tocotrienol Downregulates Mmp-9 Expression In Nsclc Cells, Rohini Sri Harshini Pindiprolu

Wayne State University Theses

Lung cancer is the leading cause of cancer death in Unites States. The main types of lung cancer are small cell lung cancer and non small cell lung cancer. NSCLC accounts for about 80% of the cases with less than 15% of patients surviving beyond 5 years. Most common causes of lung cancer are smoking, inhaling asbestos fiber, radon gas, passive smoking, air pollution, familial predisposition, prior history of lung cancer etc. Surgery, chemotherapy, targeted therapy, palliative care are commonly used treatment techniques for lung cancer. Radiation therapy is an important part of lung cancer management. The objective of this …

Contaminants Of Emerging Concern: Effects Of Known Neuroactive Agents, Antibiotics, And Chemically Uncharacterized Photodegredates On Behavior And Physiology Of Daphnia Pulex, Vibhuti Matta

Wayne State University Theses

Emerging contaminants such as pharmaceuticals and personal care products (PPCPs), herbicides, pesticides, plasticizers, fire retardants, polycyclic aromatic hydrocarbons (PAHs), and other organic waste are increasingly being detected in surface water and ground water. These contaminants can enter into the environment through wastewater treatment plant effluent and agriculture runoff. Many of these emerging contaminants tend to be biologically active at very low concentrations, typically occur in water as part of complex mixtures, and may impact biota at concentrations not detected using traditional toxicity tests (e.g. LC 50 tests).

This study focuses on utilizing novel Daphnid optical bioassays to examine the toxicity …

Protein Ubiquitination In Primary Human Skeletal Muscle Cells Under Hyperinsulinemic Hyperglycemic Conditions, Majed Abdullah Alharbi

Wayne State University Theses

Ubiquitin proteasome system is a relatively newly discovered pathway for protein degradation. Many studies have successfully pointed out the critical functions that UPS plays in regulating many physiological processes. On the other hand, recent studies suggested that abnormal UPS activities might be involved in the pathophysiology of several disorders including type 2 diabetes. However, the specific changes in UPS during the development of insulin resistance and consequently T2D are still unclear.

UPS is composed of two major steps, a reversible ubiquitin conjugation to the targeted substrate followed by proteasomal degradation of the ubiquitinated proteins. In this study, we examined the …

A Retrospective Cohort Study Of High Prevalence Of St131 Among Extended Spectrum Β-Lactamase Producing E. Coli Among Inpatients In The Metropolitan Detroit Area, Pansy Awasthy

Wayne State University Theses

ABSTRACT

HIGH PREVALENCE OF ST131 AMONG EXTENDED SPECTRUM Β-LACTAMASE PRODUCING E. COLI AMONG INPATIENTS IN THE METROPOLITAN DETROIT AREA

by

PANSY AWSTHY

2015

Advisor: Dr. Emily T. Martin

Major: Pharmaceutical Sciences

Degree: Master of Science

Objectives: E.coli ST131 multi-locus sequence type (MLST) has been associated with extended spectrum β-lactamase (ESBL) production, conferring antimicrobial resistance, with increased virulence and with healthcare-associated infection. The high prevalence of multidrug antimicrobial resistance in ESBL-producing ST131 E.coli infections creates unique challenges in the studying patient outcomes and analysis are required to study ST131 E.coli amongst a large population of ESBL-producers. Our objective was to determine …

The Effect Of Dietary Folate On Tissue Folate Status, Ghada Aoun

Wayne State University Theses

ABSTRACT

THE EFFECT OF DIETARY FOLATE ON TISSUE FOLATE STATUS.

by

Ghada Aoun

December 2015

Advisor: Dr. Diane Cabelof

Major: Nutrition & Food Science

Degree: Masters of Science

The folates are a family of structurally similar, water soluble, B vitamins that play a crucial role in human health and disease. Folate has an important role in the synthesis of DNA, DNA methylation, and cellular growth. Folate coenzymes function in accepting and donating one-carbon units in the folate metabolic pathway. Folate deficiency impairs DNA synthesis, induces cancer, and causes abnormalities such as neural tube defects and megaloblastic anemia. While scientific research …

Acoustic Cues Of Physical Formidability In Cage Fighters, Stefan Mattias-Maria Goetz

Wayne State University Theses

Across the animal kingdom, the sex that experiences the most reproductive variance tends to evolve sexually dimorphic traits—both behavioral and morphological—which aid in reproduction. Human evolution has been marked by greater male intrasexual selection and as a result, men display a variety of secondary sexual characteristics, putatively serving to enhance biological fitness. Among these, fundamental frequency, closely related to perception of pitch, among men is half that of women. Likewise, monotonicity, that is, variance in pitch across an utterance, is higher in men (i.e., women show greater variance in pitch) while formant dispersion, which gives the voice its timbre, is …

Curcumin Attenuates The Effects Of Atherogenic Diet In Aged Male Brown Norway Rats, Vindhyaja Srirajavatsavai

Wayne State University Theses

ABSTRACT

CURCUMIN ATTENUATES THE EFFECTS OF ATHEROGENIC DIET IN AGED MALE BROWN NORWAY RATS

by

VINDHYAJA SRIRAJAVATSAVAI

DECEMBER 2015

Advisor: Dr. Smiti Gupta

Major: Nutrition and Food Science

Degree: Master of Science

Cardiovascular disease (CVD) is a universal problem in modern society. Hyperlipidemia is a major risk factor for the development of cardiovascular disease. Hyperlipidemia further leads to increased oxidation and inflammation. Curcumin has long been used as a spice and food-coloring agent. In experimental animals, curcumin has shown anti-diabetic, anti-inflammatory, cytotoxic and anti-oxidant properties. In this study, Aged Brown Norway Rats were fed 1 of 3 experimental diets: a …

Novel Biochemical And Phenotypical Findings On The Nodal Signaling Components Lefty And Cripto, Amapola Balancio

Wayne State University Theses

ABSTRACT

NOVEL BIOCHEMICAL AND PHENOTYPICAL FINDINGS ON THE NODAL SIGNALING COMPONENTS LEFTY AND CRIPTO

by

Amapola Balancio

December 2014

Advisor: Dr. William Branford, Jr.

Major: Biological Sciences (Molecular and Developmental Biology)

Degree: Master of Science

Nodal, a Transforming Growth Factor-β (TGF-B), is a key regulator of proper development along with its atypical TGF-B inhibitor Lefty and its EGF-CFC co-receptor Cripto. Studies have shown that Nodal is unable to signal in the absence of a functional Cripto, indicating that it is a Nodal obligate co-receptor. In fact, one of the ways that Lefty prevents Nodal is by binding to Cripto and …

Radiation-Induced Esophagitis Is Mitigated By Soy Isoflavones, Matthew Donovan Fountain

Wayne State University Theses

Lung cancer patients receiving radiotherapy present with acute and chronic esophagitis, resulting in pain and difficulties swallowing. These effects are due to radiation injury to the normal tissues in the esophagus. Our previous studies in pre-clinical models of lung cancer and naïve mice have shown that soy isoflavones alleviates radiation-induced toxicity to normal lung, including a decrease in pneumonitis and fibrosis. In this study, we have investigated whether radiation-induced esophagitis can be reduced by soy isoflavones. C57BL/6 mice were treated with 10 Gy or 25 Gy for thoracic irradiation and soy isoflavones given daily at 1mg/mouse up to 16 weeks. …

Design And Synthesis Of Isatin-Based Caspase Inhibitors For Ruthenium Caging Applications, Kasun Chinthaka Ratnayake

Wayne State University Theses

ABSTRACT

DESIGN AND SYNTHESIS OF ISATIN BASED CASPASE INHIBITORS FOR RUTHENIUM CAGING APPLICATIONS

by

KASUN CHINTHAKA RATNAYAKE

August 2015

Advisor: Jeremy J. Kodanko, Ph.D.

Major: Chemistry (Organic)

Degree: Master of Science

Apoptosis is the energy dependent programmed cell death. Improper function of apoptosis could lead to diseases such as cancers, strokes, Alziemer’s disease. Caspases are the enzymes involved in the later stage of this process. Peptidyl and non-peptidyl caspase inhibitors have been synthesized recently. These non-peptidyl compound classes which consist of pyrrolidinyl-5-sulfo isatins have showed a greater potency against executioner caspases, caspase-3 and -7. According to literature and for further …

Combination Of Photodynamic Therapy With Fenretinide And C6-Pyridinium Ceramide Enhances Killing Of Scc17b Human Head And Neck Squamous Cell Carcinoma Cells Via The De Novo Sphingolipid Biosynthesis And Mitochondrial Apoptosis, Nithin Bhargava Boppana

Wayne State University Theses

The ceramide generated via the de novo sphingolipid biosynthesis has been shown to regulate apoptosis and cell death. The de novo sphingolipid biosynthesis includes ceramide synthase (CERS)-dependent acylation of dihydrosphingosine, giving rise to dihydroceramide, which is then converted to ceramide by a desaturase-dependent reaction. The mitochondrial pathway of apoptosis, characterized by induction of Bax associated with mitochondria and cytochrome c release/redistribution. Bcl2, an anti-apoptotic protein blocks apoptosis by inhibiting Bax. Elucidating the role of de novo sphingolipid biosynthesis and mitochondrial apoptosis in PDT, PDT+4HPR and PDT+LCL29 could help in improving the effectiveness on these anti-cancer treatments. The objective of this …

Evolution Of New Duplicate Genes In Arabidopsis Thaliana, Nicholas Curtis Marowsky

Wayne State University Theses

Abstract

Gene duplication is one of the major mechanisms by which organisms expand their genomes. The material added to the genome can then be acted upon by mutation and natural selection to increase the fitness of the species. By studying these duplicate sequences we can understand the process by which species evolve new functional genes. In a previous paper we identified 100 new duplicate genes through a genome wide comparison between A. thaliana and related species. We selected three of these new duplicate genes and investigated more closely their sequence and expression divergence from their parental gene. The three new …

Characterization Of Oral Microbiota In Xerostomic Versus Non-Xerostomic Volunteers And In Daily Samples Following Standard Oral Hygiene Practices, Chelsea Myers

Wayne State University Theses

A thesis presented on the characterization of oral microbiota in xerostomic versus non-xerostomic volunteers and in daily samples following standard oral hygiene practices. Xerostomia is a difficult and burdensome disease that can be very difficult to diagnose. Understanding the oral microbiota between these diseased and healthy (non-xerostomic) can give us great insight on new treatments and/or prevention. Goals of the study included determining whether there substantial differences in oral microbial populations between the two groups, and whether varying nightly oral hygiene practices had an impact on next-morning oral microbiota titers or composition. Microbial loads were determined by qPCR using broad-spectrum …

Developmental Evolution Of The Visual System In The Cave-Adapted Small Carrion Beetle Ptomaphagus Hirtus, Jasmina Kulacic

Wayne State University Theses

Extensive research has been done to date on Drosophila and Tribolium eye development; however, not much is known about the molecular basis of development of extremely reduced and modified eyes in cave insects. Ptomaphagus hirtus represents an emerging model system for studying the changes at the molecular level that occurred during the evolutionary adaptation of the eye to the cave environment. Therefore, I have started exploring the morphology and organization of the reduced P. hirtus eyelet, using immunohistochemistry, laser scanning microscopy, and ultrastructural imaging approaches. My findings demonstrate that the adult eyelet lacks ommatidial subdivision and has a thick, clear …

Effect Of Metformin On Global Phosphorylation Profiles Of Primary Skeletal Muscle Cells Derived From Overweight/Obese Insulin Resistant Human Participants, Nishit Shah

Wayne State University Theses

Metformin is a drug from the biguanide class and it has been in use for the treatment of type 2 diabetes for a long time, and it can improve insulin sensitivity in skeletal muscle. However, the mechanism for metformin’s action is unclear. Phosphatases and kinases, and their subunits are the proteins required for dephosphorylation and phosphorylation of proteins in cells during various signaling pathways. Phosphorylation studies of proteins from primary cell culture derived from skeletal muscle tissue from obese/overweight insulin resistant participants will help to understand the regulation of phosphorylation in phosphatases and kinases by metformin.

In the current research, …

Exploring Novel Daptomycin Combinations With Β-Lactam Against Susceptible & Non-Susceptible Enterococcus Species, Animesh Raut

Wayne State University Theses

EXPLORING DAPTOMYCIN COMBINATION WITH β-LACTAM SYNERGY AGAINST SUSCEPTIBLE AND NON-SUSCEPTIBLE ENTEROCOCCI SPECIES

by

ANIMESH RAUT

August 2015

Advisor: Dr. Michael J. Rybak

Major: Pharmaceutical sciences

Degree: Master of Science

Objective: Enterococcus faecalis and Enterococcus faecium are generally resistant to daptomycin and β-lactam antibiotics. However, documented in vitro data suggests synergy between several β-lactam antibiotics and daptomycin against resistant organisms. Primary goal of the study was to check various combinations of β-lactam antibiotics with daptomycin (DAP) and assess the potential of synergy and conclude which could be the superior combination. Study also evaluated potential of β-lactam antibiotics to enhance activity of …

The Effects Of Motility And Chemotaxis On Vibrio Cholerae Colonization In Zebrafish, Paula Dietz

Wayne State University Theses

Vibrio cholerae, the cause of the diarrheal disease cholera, is a gram-negative, curved rod-shaped bacterium, with a single polar flagellum. V. cholerae is naturally found in aquatic environments and is highly motile. When it enters a human host, V. cholerae uses flagellar motility to pass through the stomach and into the small intestine. Once in the small intestine, motility genes are downregulated and virulence gene expression is upregulated. V. cholerae motility and chemotaxis effects have not yet been studied in a zebrafish model, a natural host of this bacterium. We hypothesize that V. cholerae in frame deletions of vital motility …

Potential Antidiabetic And Antioxidant Activitys Of Selected Medicinal Plants, Paba Surangi Sathsara Saranasingha Edirisuriya

Wayne State University Theses

Explore traditionally used medicinal plants for diabetes mellitus would be beneficial to find an alternative option for controlling global diabetic prevalence. Present study aims to compare and identify potential antidiabetic activity in Tinospora cordifolia, Gymnema sylvestre and Aegle marmelos. Fifty percent acetone and ethyl acetate extracts of each plant were studied for anti-diabetic activity using different assays (ORAC, DPPH, ABTS, TPC, α-glucosidase inhibition). Total phenolic content and anti oxidant properties were significantly different among three plants. Tinospora cordifolia ethyl acetate extract possessed significantly higher anti oxidant activity and total phenolic content. DPPH and ABTS results were significantly correlated with each …

Hiv Integrase Mechanisms Of Resistance To Raltegravir, Elvitegravir, And Dolutegravir, Kyla Nicole Ross

Wayne State University Theses

ABSTRACT

HIV INTEGRASE MECHANISMS OF RESISTANCE TO RALTEGRAVIR, ELVITEGRAVIR, AND DOLUTEGRAVIR

by

KYLA ROSS

December 2015

Advisor: Dr. Ladislau Kovari

Major: Biochemistry and Molecular Biology

Degree: Master of Science

HIV-1 integrase (HIV-1 IN or IN) is a multimeric enzyme that integrates the HIV-1 genome into the chromosomes of infected CD4+ T-cells. Currently there are three FDA approved HIV-1 IN strand transfer inhibitors (INSTIs) used in clinical practice: raltegravir (RAL), elvitegravir (ELV), and dolutegravir (DTG). The [Q148H], [Q148H, G140S], [Q148R], [Q148R, G140A] and [N155H, E92Q] mutations decrease IN susceptibility to RAL and ELV and may result in therapeutic failure. As an …

Antimicrobial-Resistant Listeria Species From Retail Meat In Metro Detroit, Liziane Da Rocha

Wayne State University Theses

A total of 138 Listeria isolates, including 58 Listeria welshimeri, 44 Listeria monocytogenes, and 36 Listeria innocua, from retail meat were characterized by antimicrobial susceptibility tests against nine antimicrobials. In addition, the 44 L. monocytogenes were analyzed by serotype identification using PCR and genotyping using pulsed-filed gel electrophoresis (PFGE). Resistance to one or two antimicrobials was observed in 32 Listeria (23.2%). No multidrug resistance was identified. Tetracycline resistance was the most common resistance phenotype and identified in 22 Listeria isolates. Low prevalence of resistance to ciprofloxacin, erythromycin, gentamicin, and vancomycin was also detected. L. innocua demonstrated the highest overall prevalence …

Plsi: A Computational Software Pipeline For Pathway Level Disease Subtype Identification, Michele Donato

Wayne State University Theses

It is accepted that many complex diseases, like cancer, consist in collections of distinct genetic diseases. Clinical advances in treatments are attributed to molecular treatments aimed at specific genes resulting in greater ecacy and fewer debilitating side effects. This proves that it is important to identify and appropriately treat each individual disease subtype. Our current understanding of subtypes is limited: despite targeted treatment advances, targeted therapies often fail for some patients. The main limitation of current methods for subtype identification is that they focus on gene expression, and they are subject to its intrinsic noise. Signaling pathways describe biological processes …

The Contribution Of The Melanin Pathway To Overall Body Pigmentation Changes During Ontogenesis Of Periplaneta Americana, Thomas Roger Lemonds

Wayne State University Theses

Pigmentation is one of the most diverse and distinguishable features of insect morphology. The most prominent colors observed in insects are black or brown, whose production is attributed to the melanin pathway. At present, though, the contribution of this pathway to overall body pigmentation throughout ontogenesis is still lacking. To address this question we examined the roles of four key melanin genes (TH, DDC, ebony, and aaNAT), in embryonic and post-embryonic development of Periplaneta americana. Our results show show that while the melanin pathway plays no role during the earliest nymphal stages, it is required during the later stages of …

Synergetic Effect Of Permethrin And Dmh On Anti-Oxidation And Damage Response Genes, Karim Mohamed

Wayne State University Theses

The objective of this study was to evaluate the Synergetic Effect of Permethrin and 1,2-Dimethylhydrazine (DMH) on Anti-oxidation and Damage Response genes. The animal models used for this study were 8 week old C57/blk6 female mice. The mice were fed a Folate Adequate (FA) diet. At 8 weeks, the mice were intraperitoneally injected with pesticides. Three 8-week old female mice were injected intraperitoneally with a mix of cis and trans permethrin (75%:25% respectively) at 30% median lethal dose (96 mg/kg body weight). Permethrin was dissolved in corn oil and injected 24 hours before sacrifice. In three other mice, DMH was …

Methodology For Performing Whole Body Pmhs Underbody Blast Impact Testing, And The Corresponding Response Of The Hybrid Iii Dummy And The Finite Element Dummy Model Under Similar Loading Condition, Karthik Somasundaram

Wayne State University Theses

In recent wars, the use of improvised explosive devices and landmines has dramatically increased as a tactical measure to counter armored vehicles. These weapons not only deform and damage the vehicle structure but also produce serious vertical deceleration injuries to mounted occupants. The reported injury patterns largely differ from those in an automotive crash and are often more severe than those in other vertical loading scenarios such as pilot seat ejection, helicopter crash, parachute landing and fall from height. High kinetic energy predominately along the principal vertical (Z-axis) over a short duration makes the underbody blast (UBB) loading conditions unique …