Life Sciences Commons^™

Uracil Accumulation In Folate Depleted Mouse Embryonic Fibroblasts, Eneida Doko

Wayne State University Theses

Folate is a water-soluble vitamin B that plays a critical co-enzyme in the de novo nucleotide synthesis and other biochemical processes including DNA metabolism, DNA repair, DNA methylation, and cellular growth. Folate deficiency has been associated to increase the risk of neural tube defects (NTDs) and cancers of the lung, breast, colon, cervix, esposphagus and brain. Most importantly, folate deficiency has been shown to increase uracil misincorporation into DNA and therefore induce DNA damage repaired by the base excision repair (BER) pathway. In response to folate depletion, levels of thmidylate decrease in the deoxyribonucelotide pool, resulting in uracil being misincorporation …

Novel Inhibitors Of The Bacterial De Novo Purine Biosynthesis Enzymes, N5-Carboxyaminoimidazole Ribonucleotide Synthetase And Mutase, Maria V. Fawaz

Wayne State University Theses

Antibiotic resistance has seen a significant increase during the past decade. The increasing frequency of the drug-resistant bacterial infections has amplified the need for novel antimicrobial agents. De novo purine biosynthesis is one area that has great potential for antibacterial drug development because this pathway is different in microorganisms versus humans. The difference in the pathway is centered on the synthesis and utilization of the purine intermediate N⁵-carboxy-5-aminoimidazole ribonucleotide (N⁵-CAIR). Previous studies have shown that N⁵-CAIR is a key intermediate in purine biosynthesis in bacteria, yeast and fungi, but not in humans. N^{5 …}

Modulation Of Anti-Tumor Immune Response By Tgf-Β-Inducible Early Gene 1 (Tieg1), Andi Cani

Wayne State University Theses

Cancer immunotherapy has had limited clinical efficacy partly because regulatory T cells (Treg) suppress the immune response to tumor-associated antigens. Inducible regulatory T cells (iTreg), which are converted from naïve CD4 T cells by TGF-β, an abundant cytokine in the tumor microenvironment, may contribute to this immune suppression. Induction of Foxp3 by TGF-β is mediated by the transcription factor TIEG1 and abrogation of this protein prevents Foxp3 expression. We are testing the hypothesis that blockade of TIEG1 to prevent iTreg conversion will enhance immune response in DNA vaccination to the tumor associated antigen Her-2. Wild type and TIEG1 knockout mice …

Investigation Of A 16s Rna Central Domain Pseudoknot, Jenna Marie Jasinski-Bolak

Wayne State University Theses

X-ray crystallography of the prokaryotic 30S ribosomal subunit revealed a myriad of complex RNA-RNA, RNA-protein, and protein-protein interactions. Among these are several phylogenetically conserved RNA pseudoknots. Pseudoknots are structurally and functionally diverse RNA secondary structures. They are generally formed by two short complimentary sequences separated by many bases of single stranded regions or loops. These relatively simple folds are often yield complex structures that are key components of functionally important conformational changes in RNA structure. One such pseudoknot is located in the central domain of the 16S rRNA.

The central domain pseudoknot is formed by Watson-Crick base pairing between G570-C866 …

Mrna Granules And Ischemic Preconditioning, Michelle Rei Smith

Wayne State University Theses

Brain ischemia and reperfusion that occurs after stroke and cardiac arrest, causes translation arrest (TA) in neurons which is irreversible in neurons that will undergo delayed neuronal death. TA is linked to mRNA granules, which are involved in ischemia-induced stress genes translation. Ischemic preconditioning (IPC) is the most protective response known that protects neurons from a lethal ischemic insult. In this thesis I studied the effects of (1) sublethal durations of ischemia, (2) IPC and (3) cycloheximide (CHX) on the formation of mRNA granules at 1 hour of reperfusion and the colocalization of HuR in the mRNA granules. All durations …

Disrupting Cxcr2 Macromolecular Complex Pdz-Domain Interactions During Inflammatory Chemotaxis, Marcello Castelvetere

Wayne State University Theses

Neutrophils are the body's first responders to inflammation, being the most abundant white blood cell type in circulation and they quickly initiate an immune response through chemokine signaling. Inflammatory chemokines signal via their receptor CXCR2, which initiates an inflammatory response, recruiting leukocytes to sites of inflammation. Chemokine signaling is important for proper host protection, yet uncontrolled activity is responsible for a variety of pathological conditions: including rheumatoid arthritis, ischemia-reperfusion injury, arteriosclerosis, multiple sclerosis, psoriasis, inflammatory bowel disease, and allergic reactions.

In this report I show a CXCR2 macromolecular signaling complex exists in neutrophils, containing NHERF1 and PLCβ2. I also demonstrate …

The Role Of Uracil-Dna Glycosylase And Folate In The Repair Of Dna, Sarah Talal Dubaisi

Wayne State University Theses

Abstract

Role of Uracil DNA-Glycosylase and Folate

In the Repair of Oxidative Damage

By

Sarah Dubaisi

May2012

Advisor: Dr. Diane Cabelof

Major: Nutrition and Food Science

Degree: Masters of Science

The impact of DNA damage on genomic integrity has been widely investigated due to its association with cancer and ageing. DNA repair pathways play a critical role in preserving the genomic integrity and protecting the cells against DNA damage caused by oxidative stress and folate deficiency. Base Excision Repair (BER) is one of the major pathways involved in the cellular response to DNA damage, primarily the damage caused by oxidative …

The Use Of Metabolomics To Investigate Biomarker Profiles As Potential Early Risk Factors For Development Of Type Ii Diabetes Mellitus, Jennelle Lynn Arnew (Getty)

Wayne State University Theses

ABSTRACT

THE USE OF METABOLOMICS TO INVESTIGATE BIOMARKERS PROFILES AS POTENTIAL EARLY RISK FACTORS FOR DEVELOPMENT OF TYPE II DIABETES

by

JENNELLE ARNEW

MAY 2012

Advisor: Dr. Smiti Gupta

Major: Nutrition and Food Science

Degree: Masters of Science

Type 2 Diabetes affects an estimated 17.5 million individuals in the United States and is considered to be one of the most pressing public health issues of our time. To date, the exact cause of type 2 diabetes remains unclear, however, it is considered to be an interplay between environmental and genetic factors. Emerging technologies for metabolomics analysis increases the capacity to …

Football Helmet Fitment And Its Effect On Helmet Performance, Ron Jadischke

Wayne State University Theses

A method and system to objectively quantify helmet fitment was designed and developed. It measures the pressure between the energy-absorbing material in the helmet and the athlete's head. This system is also capable of measuring surface pressure during impact events. A volunteer-based field study was conducted to quantify how helmets were fitting athletes in a real-life setting. The helmets fit athletes in varying degrees of tightness and evenness. Most athletes (59%) had the highest pressures in the frontal area and 29% had the highest pressure in the occipital area. A large-sized helmet on the Hybrid III headform represented how most …

Contact Pressure Distribution Of Osteochondral Defects Of The Knee: Effects Of Non-Vertical Walls, Scott Ensminger

Wayne State University Theses

Purpose: To examine the relationship between well-shouldered osteochondral defects and

defects of different geometries by studying their effects on rim stress concentration and

load redistribution in the human knee.

Methods: Ten fresh-frozen cadaveric knees were mounted at 30° of flexion in a materials

testing machine. Digital electronic pressure sensors were placed in the medial and lateral

compartments of the knee. Dynamic pressure readings were recorded throughout the

loading and holding phases as each knee was loaded to 700N and held for 5 seconds.

Artificial defects were created in each knee to simulate well-shouldered defects and

beveled-defects. Loading was repeated for …

The Prdm Gene Apoptix Antagonizes Programmed Cell Death In Tribolium, Zahabiya Husain

Wayne State University Theses

Previous studies in holometabolous insects have shown that programmed and cell proliferation play important roles in insect metamorphosis. To elucidate the function of the newly identified Tribolium Prdm gene Apoptix (Apox) I performed a detailed analysis of Apox knockdown effects in the embryo, the pupa and the adult eye. My results revealed that Apox is required for the survival of retinal tissue after onset of differentiation and also generally in tissues which experience high amounts of proliferation and differentiation during pupal development. Further, combinatorial knockdown of Apox and initiator caspases produced evidence that Apox specifically protects from programmed cell death …

Pax6 Is Required For The Development Of The Lateral Procephalon In Tribolium, Qing Luan

Wayne State University Theses

In Tribolium, combinatorial knockdown of the Pax6 orthologs eyeless (ey) and twin of eyeless (toy) affects the peripheral visual system but also other areas of the dorsal larval head capsule. To elucidate the role of Pax6 genes during Tribolium embryonic head development in detail, we performed an extensive analysis of cuticle

elements, brain anatomy, embryonic head morphogenesis and developmental marker gene expression. Our results reveal that Pax6 is required for the development of a large contiguous area of the lateral anterior head, morphologically addressed as the embryonic head lobes, which encompass the neuroectodermal precursor tissues of the visual system, parts …

Investigating The Glutamine-Trna (Glutamine) Synthesis Appartus Of The Human Pathogen Helicobacter Pylori, Nilesh Joshi

Wayne State University Theses

INVESTIGATING THE GLUTAMINE-TRNA (GLUTAMINE) SYNTHESIS APPARTUS OF THE HUMAN PATHOGEN HELICOBACTER PYLORI

by

NILESH JOSHI

August 2012

Advisor: Tamara L. Hendrickson

Major: Chemistry

Degree: Master of Science

Accurate protein biosynthesis is a vital process to all cellular life. Aminoacyl-tRNAs are at the heart of this process: A correctly formed aminoacyl-tRNA is critical for protein biosynthesis. Organisms have evolved many mechanisms to repair misacylated tRNAs before they cause errors in protein biosynthesis, thus maintaining the integrity of the genetic code. The human pathogen Helicobacter pylori (H. pylori) synthesizes Glu-tRNAGln as an intermediate to producing Gln-tRNAGln. This misacylated intermediate could cause lethal …

Purification Of Alpha-Glucosidase Inhibitors From Grape Extract, Gayle M. Shipp

Wayne State University Theses

ABSTRACT

PURIFICATION OF ALPHA-GLUCOSIDASE INHIBITORS FROM GRAPE EXTRACT

by

GAYLE SHIPP

August 2012

Advisor: Dr. Kevin Zhou

Major: Nutrition and Food Science

Degree: Master of Science

Diabetes and its complications are steadily growing and remain major causes of morbidity and mortality in the U.S. Intestinal á-glucosidases play a crucial role in controlling postprandial blood glucose. For this reason, one attractive prevention and/or treatment strategy for type-2 diabetes is the inhibition of á-glucosidase. The effectiveness of á-glucosidase inhibitors (AGI's) for diabetes treatment is well documented in numerous animal and human clinical studies. Grape pomace extract (GPE) has recently found in our …

Psychological And Physiological Responses Of Males Viewing Same Gender Advertisements, Phil Dittmer

Wayne State University Theses

Body image has been a well established research topic in the field of sport and exercise psychology. However, most of the literature focuses on female body image and ignores male body image. It has been established by current literature that men react the same way as females when presented with pictures of the ideal body of the same sex; a negative body image affect. However, it is unknown in both females and males if this negative body image affect is a strong enough response to elicit a physiological stress response. This master's thesis serves as an explorative project to bridge …

The Effects Of Oil Palm Phenolics On Inflammation And Oxidative Stress In Relation To Amyloid Beta Plaques In Fad-Mutant And Wild Type B103 Cells, Lindsay Michelle Godsey

Wayne State University Theses

Alzheimer's disease (AD) affects approximately 35.6 million people in the world today (35). It is expected that by year 2050, an individual will develop AD every 33 seconds (8). Unfortunately, the etiology is not well known. Familial Alzheimer's disease (FAD) occurs due to specific genetic mutations, making it possible to replicate them in cells. Using B103 rat neuroblastoma cells transfected with a cDNA construct, wild type cells and FAD mutant cells were used in this research.

Natural ingredients such as oil palm phenolics (OPP) contain antioxidants. After finding the optimal experimental parameters, OPP was found to aid in the destabilization …

The Spliceosomal Protein Prp8 Stabilizes A Compact Conformation Of The U2-U6 Complex, Subasinghe Appuhamilage Lemintha Imali Subasinghe

Wayne State University Theses

The spliceosome is a large, RNA-protein complex that catalyzes pre-mRNA splicing during mRNA maturation. The RNA components (small nuclear RNA; snRNAs) of the spliceosome have been well studied and are believed to be involved in the splicing catalysis. Although proteins are essential for splicing, they may not be directly involved in catalysis. Among hundreds of proteins, Prp8 is the only protein that interacts with all of the catalytically important snRNAs. Therefore, it is hypothesized that Prp8 may catalyze splicing either by directly participating in catalysis or by stabilizing the conformation of the catalytically active spliceosome. In order to test whether …