Digital Commons Network^™

Histone Deacetylase 1: Mutagenesis And Small Molecule Studies, Magdalene Wambua

Wayne State University Dissertations

Histone deacetylase 1 (HDAC1) has been linked to cell growth and cell cycle regulation, which makes it a widely recognized target for anticancer drugs. The 14 Å channel of Class 1 HDAC isotypes has long being hypothesized to be the exit cavity for acetate following deacetylation. The amino acids lining this cavity are very similar among the HDAC isoforms, suggesting the role of the cavity is relevant to all HDACs proteins Importanly, HDAC1 selective inhibitors designed to fit the 14Å channel have been designed. To understand the importance of the 14Å channel to HDAC1 activity, we used an alanine scan …

The Role Of Cardiolipin In Iron Homeostasis And Glutathione Metabolism, Vinay A. Patil

Wayne State University Dissertations

Cardiolipin (CL) is the signature phospholipid of mitochondrial membranes, where it is synthesized locally and plays a critical role in mitochondrial bioenergetic functions. Inside the mitochondria, CL is a critical target of mitochondrial generated reactive oxygen species (ROS) and regulates signaling events related to apoptosis and aging. CL deficiency causes perturbation of signaling pathways outside the mitochondria, including the PKC-Slt2 cell integrity pathway and the high osmolarity glycerol (HOG) pathway, and is a key player in the cross-talk between the mitochondria and the vacuole. The importance of CL in human health is underscored by the observation that perturbation of CL …

Characterization Of Antimicrobial-Resistant Staphylococcus Spp. In Food Animals And Retail Meat, Kanika Bhargava

Wayne State University Dissertations

Antimicrobial resistance in Staphylococcus spp. is a worldwide epidemic concern in hospital and community settings. Food animals and retail meat are important reservoirs of these pathogens that can pose potential threat to humans. In this dissertation, we aimed to investigate the molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Coagulase-negative Staphylococci (MRCoNS) in food animals and retail meat to provide insight into the role of agricultural environment in transmitting bacteria of human clinical significance. Furthermore, the potential application of phytochemicals as antimicrobials and antimicrobial adjuvants to control MRSA infections was explored.

CoNS recovered from food animals were characterized by …

Striatal Dopamine Dynamics Upon Manganese Accumulation, Madiha Khalid

Wayne State University Dissertations

STRIATAL DOPAMINE DYNAMICS UPON MANGANESE ACCUMULATION

by MADIHA KHALID

August 2013

Advisor: Dr. Tiffany Mathews

Major: Chemistry (Analytical)

Degree: Doctor of Philosophy

Although manganese (Mn) is fundamental for many biological processes, exposure to excess amounts leads to a neurological disorder termed manganism. Due to its symptomatic similarity to Parkinson's disease, as well its preferential accumulation in dopamine rich brain regions, alterations in the dopamine system are implicated in the onset of manganism. In my research, Mn overexposure is mimicked via subcutaneous administration of manganese chloride to C57BL/6 mice over the course of seven days using a protocol that has been …

Linking Environmental Toxicant Exposure To Diabetes Susceptibility, Jannifer Beth Tyrrell

Wayne State University Dissertations

An important and unresolved question in the environmental health field is whether exposure to common environmental toxicants, such as dioxin and heavy metals like Pb, increase the risk of developing diabetes, especially in combination with other common metabolic stressors such as obesity.

Previous studies suggested that dioxin exposure increased peripheral insulin resistance but did not appear to cause fasting hyperglycemia or elevated hepatic glucose output. In concordance with those findings we observed that dioxin treatment caused a strong suppression of the expression of the key hepatic gluconeogenic genes PEPCK and G6Pase. However, this suppression was not solely mediated by the …

The Effect Of Proalgazyme And Its Subfractions On Lipid Metabolism In Diet Induced Hypercholesterolemic Hamsters: Correlation With Plasma Metabolomic Profile, Andreea Geamanu

Wayne State University Dissertations

ABSTRACT

THE EFFECT OF PROALGAZYME AND ITS SUBFRACTIONS ON LIPID METABOLISM IN DIET INDUCED HYPERCHOLESTEROLEMIC HAMSTRES:

CORREALTION WITH PLASMA METABOLOMIC PROFILE

by

ANDREEA GEAMANU

December 2013

Advisor: Dr. Smiti Gupta

Major: Nutrition and Food Science

Degree: Doctor of Philosophy

Background: Plasma HDL cholesterol levels are inversely related to cardiovascular disease, which is the leading cause of death worldwide. This study investigated the preventative effect of an algae infusion, ProAlgaZyme (PAZ) and its subfractions (F1, F2, F3, F4) on plasma HDL in a hamster model. Further, the study aimed to identify the biologically active fraction of PAZ and to determine the …

Desensitization Of Basal Cell Carcinoma To The Anti-Tumoral Effect Of Vitamin D, Rawia Khasawneh

Wayne State University Dissertations

The relationship between Vitamin D and NMSC is not very clear. Most of human studies in literature in regards to vitamin D and NMSC are epidemiological which are inconsistent and inconclusive. Mechanistic studies about BCC are few, and mostly are animal models or cell cultures. The main goal for this study is to interpret the impact of vitamin D status on the onset and progression and possibly treatment of basal cell carcinoma. Three tissue samples were collected from BCC patients (Cancer, Proximal, and Distal), and from cancer-free individuals from southeast Michigan. This study design helps identifying alterations in the genetic …

Synthesis And Application Of Atp Analogs For Phosphorylation-Dependent Kinase-Substrate Crosslinking, Satish Kumar Garre Venkata Raghavendra

Wayne State University Dissertations

Phosphorylation is an important post-translational modification that plays a key role in a variety of signaling cascades and cellular functions. Kinases phosphorylate protein substrates in a highly regulated manner and are promiscuous. Understanding kinase-substrate specificity has been challenging and there is a need for new chemical tools. To this end we developed -phosphate modified ATP photocrosslinking analogs ATP-ArN3 and ATP-BP, that crosslink substrate and kinase in a phosphorylation dependent manner. We have successfully demonstrated that ATP-ArN3 and ATP-BP can be used with natural kinase and substrates using cell lysates in vitro. We used our approach to identify novel kinases of …

Sleep Homeodynamics And Wellbeing In Asymptomatic Hiv-Seropositive African American Women, Tabetha Lynn Gayton

Wayne State University Dissertations

SLEEP HOMEODYNAMICS AND WELLBEING IN ASYMPTOMATIC HIV–SEROPOSITIVE AFRICAN AMERICAN WOMEN

by

TABETHA LYNN GAYTON

December 2013

Advisor: Hossein N. Yarandi, PhD

Major: Nursing (Urban Health)

Degree: Doctor of Philosophy

BACKGROUND: HIV–related sleep disruption is a common complaint of persons with HIV infection. With the demographical shifts, African American women have now emerged as one of the fastest growing HIV populations today, yet they remain a vulnerable and underrepresented population in the sleep literature.

OBJECTIVE: The purpose of this pilot study was to explore the dynamics of HIV–related sleep disruption and wellbeing in asymptomatic HIV–seropositive AA women of childbearing age within …

The Diagnosis Narratives & The Healing Ritual, James Peter Meza

Wayne State University Dissertations

ABSTRACT

THE DIAGNOSIS NARRATIVES & THE HEALING RITUAL

by JAMES PETER MEZA

December 2013

Advisor: Dr. Andrea Sankar

Major: Anthropology (medical)

Degree: Doctor of Philosophy

The goal of this dissertation was to describe healing practices in the setting of clinical encounters between patients and doctors. The theoretical background for this research began with the theory of the mind and using concepts from cognitive anthropology described the anthropological self as distinguished from person or identity. Additionally, the conceptual framework of cognitive anthropology was used to describe narrative theory. Narrative theory in the form of the narrative structure of experience, particularly the …

Evaluating Chemical Toxicity: A Novel Behavioral Assay Using Daphnia, Maya A. Zein

Wayne State University Dissertations

Pharmaceuticals, and personal care products (PPCPs), and other emerging contaminants, such as pesticides, are increasingly being detected in the environment. Important sources of these contaminants are waste water treatment plants and agriculture. Many of these contaminants are biologically active at low concentrations, and may impair physiological processes in exposed organisms, alter reproductive, endocrine or immune system function, and ultimately affect fitness and survival. These chemicals are often found in the environment as complex mixtures, and this complicates their evaluation of their toxicity. There is a need for high-throughput assays to rapidly assess the toxicity of these emerging contaminants. A behavioral …

Two-Time-Scale Systems In Continuous Time With Regime Switching And Their Applications, Yousef Talafha

Wayne State University Dissertations

This dissertation is focuses on near-optimal controls for stochastic differential equation with regime switching. The random switching is presented by a continuous-time Markov chain. We use the idea of relaxed control and mean of martingale formulation to show a weak convergence result.

The first chapter is devoted to the study of stochastic Li´enard equations with random switching. The motivation of our study stems from modeling of complex systems in which both continuous dynamics and discrete events are present. The continuous component is a solution of a stochastic Li´enard equation and the discrete component is a Markov chain with a finite …

Pubh 560.50: Environmental And Rural Health, Tony Ward

University of Montana Course Syllabi

No abstract provided.

Public Buildings And Civic Benefactions In Western Rough Cilicia: Insights From Signaling Theory, Luann Wandsnider

Department of Anthropology: Faculty Publications

In the Hellenistic and Roman world of the eastern Mediterranean, Greek and Greco-Roman cities came to be defined by their physical cityscape. These buildings were constructed by specific city institutions, such as the council and the assembly, and financed through city funds, mass subscription and, importantly, public benefactions. Public benefactions, which also included support for festivals and competitions, were made by certain elite and usually wealthy individuals to the benefit of a defined community of citizens (and sometimes non-citizens, as in the case of fortification walls). Institutions within the benefiting community, again the council and the assembly, acknowledged these gifts …

Reducing Assembly Complexity Of Microbial Genomes With Single-Molecule Sequencing, Sergey Koren, Gregory P. Harhay, Timothy P. L. Smith, James L. Bono, Dayna M. Harhay, Scott D. Mcvey, Diana Radune, Nicholas H. Bergman, Adam M. Phillipy

Roman L. Hruska U.S. Meat Animal Research Center: Reports

Background: The short reads output by first- and second-generation DNA sequencing instruments cannot completely reconstruct microbial chromosomes. Therefore, most genomes have been left unfinished due to the significant resources required to manually close gaps in draft assemblies. Third-generation, single-molecule sequencing addresses this problem by greatly increasing sequencing read length, which simplifies the assembly problem.

Results: To measure the benefit of single-molecule sequencing on microbial genome assembly, we sequenced and assembled the genomes of six bacteria and analyzed the repeat complexity of 2,267 complete bacteria and archaea. Our results indicate that the majority of known bacterial and archaeal genomes can be …

Differences In X-Chromosome Transcriptional Activity And Cholesterol Metabolism Between Placentae From Swine Breeds From Asian And Western Origins, Steve R. Bischoff, Shengdar Q. Tsai, Nicholas E. Hardison, Alison A. Motsinger-Reif, Bradley A. Freking, Dan J. Nonneman, Gary A. Rohrer, Jorge A. Piedrahita

Roman L. Hruska U.S. Meat Animal Research Center: Reports

To gain insight into differences in placental physiology between two swine breeds noted for their dissimilar reproductive performance, that is, the Chinese Meishan and white composite (WC), we examined gene expression profiles of placental tissues collected at 25, 45, 65, 85, and 105 days of gestation by microarrays. Using a linear mixed model, a total of 1,595 differentially expressed genes were identified between the two pig breeds using a false-discovery rate q-value ≤0.05. Among these genes, we identified breed-specific isoforms of XIST, a long non-coding RNA responsible X-chromosome dosage compensation in females. Additionally, we explored the interaction of placental gene …

Motherhood And Love: Beyond The Gendered Stereotypes Of Theology, Sandra Sullivan-Dunbar

Theology: Faculty Publications and Other Works

This article reviews the book Motherhood and Love: Beyond the Gendered Stereotypes of Theology, by Cristina Grenholm.

Genomic Correlates Of Relationship Qtl Involved In Fore- Versus Hind Limb Divergence In Mice, Mihaela Palicev, Gunter P. Wagner, James P. Noonan, Benedikt Hallgrimsson, James M. Cheverud

Biology: Faculty Publications and Other Works

Divergence of serially homologous elements of organisms is a common evolutionary pattern contributing to increased phenotypic complexity. Here, we study the genomic intervals affecting the variational independence of fore- and hind limb traits within an experimental mouse population. We use an advanced intercross of inbred mouse strains to map the loci associated with the degree of autonomy between fore- and hind limb long bone lengths (loci affecting the relationship between traits, relationship quantitative trait loci [rQTL]). These loci have been proposed to interact locally with the products of pleiotropic genes, thereby freeing the local trait from the variational constraint due …

Is Reliable-Social-Scholarlyo-Editing An Oxymoron, Peter Shillingsburg

Center for Textual Studies and Digital Humanities Publications

A critique of humanities digital archive and text projects holding them to standards of iconographical and textual accuracy and a criticism of collaborative projects for posting not-ready-for-prime-time versions of work that passes for finished by some while demanding help from others to bring up to usable standards. Suggests minimal standards for digital textual projects and outlines principles for collaborative work.

Brain Ras: Hypertension And Beyond, Marc De Gasparo, Robert C. Speth, Ovidiu C. Baltatu, Patrick Vanderheyden

HPD Articles

No abstract provided.

(In)Formal Distinction In Urban Istanbul: Evaluating Spatial Performance, Hannah A. Breshears

Inquiry: The University of Arkansas Undergraduate Research Journal

As globalization continues to draw the world into closer economic and intellectual dependence, massive tracts of informally designed communities in Istanbul are being cleared to accommodate the growing infrastructure of the modern, tourism-driven city This attempt to purge the city of its ‘squatter’ heritage is startling and raises questions of cultural integrity in urban development. Istanbul’s desire for expanded global investment is particularly apparent in the object of this study, the blended district of Kartal. This study measures, compares, and evaluates spatial performance of formal and informal neighborhood spaces, but makes no formal attempt to draw normative prescriptive conclusions. The …

Environments, Externalities And Ethics: Compulsory Multinational And Transnational Corporate Bonding To Promote Accountability For Externalization Of Environmental Harm, Matthew A. Susson

Buffalo Environmental Law Journal

Developing nations often look to their bounty of natural resources or willing labor as a means of attracting international investors. While national and local governments frequently perceive the arrival of a multinational corporate presence as a boon to their economy, the potential for government instability ineffectiveness or corruption may facilitate environmentally exploitive corporate practices. Furthermore, residents of the subject nation may be left without proper legal recourse. Legislators have made various efforts in both the United States and abroad to propound Corporate Codes of Conduct to address such concerns, but despite laudable intentions, features of the increasingly global economy "accentuate …

Undergraduate Review, Vol. 9, 2012/2013

Undergraduate Review

No abstract provided.

Defending Your Dna: Combating Threats Both Foreign And Domestic, James Mcisaac

Undergraduate Review

We are under constant assault from forces capable of damaging our DNA. The genetic code of DNA is made up of four nucleotides: adenine (A) which bonds with thymine (T) and guanine (G) which bonds with cytosine (C). If something happens to upset this normal pairing or the nucleotides themselves, our body must spring to action and respond to the damage. When damage to nucleotides prevents the normal replication machinery from doing its job, enzymes like the Y-family polymerases are called in. A special mechanism allows them to identify damage and insert the correct nucleotide or bypass the lesion to …

Characterization And Investigation Of At2g42005 In Arabidopsis Thaliana, A Nematode-Induced Transporter, Rachel Medina

Undergraduate Review

Meloidogyne incognita is an obligate parasitic roundworm that infects the root tips of a wide variety of host plants. This infection directly affects the crop production globally with the loss of crops such as tomatoes, carrots, and potatoes. Nematode infection manipulates the plant root by altering gene expression for nematode benefit. Genes such as At2g42005, a putative amino acid transporter, have been found to be upregulated by nematode infection. Characterizing the role of the At2g42005 gene in Arabidopsis thaliana is the first step to understanding its function in nematode infection. The role of At2g42005 were explored by creation of a …

Early To Bed, Early To Rise: How Changing To An Earlier School Start Time Affects Sleep Patterns And Cognitive Functioning In School-Aged Children, Laura Pistorino

Undergraduate Review

The purpose of this project was to elucidate the impact of earlier school start times on elementary school children. Research demonstrates that adolescents are chronically sleep deprived due to shifting biological rhythms and early school start times. As a result, some schools have restructured their schedules to allow for later start times for middle and high school students. This change has inadvertently resulted in earlier start times for the elementary school students. Although studies demonstrate a positive impact of later start times for adolescents, no studies have examined younger children. This project, therefore, examined the effect of an earlier start …

In Silico Investigation Of Ph-Dependence Of Prolactin And Human Growth Hormone Binding To Human Prolactin Receptor, Lin Wang, Shawn Witham, Zhe Zhang, Michael E. Hodsdon, Emil Alexov

Publications

Experimental data shows that the binding of human prolactin (hPRL) to human prolactin receptor (hPRLr-ECD) is strongly pH-dependent, while the binding of the same receptor to human growth hormone (hGH) is pH-independent. Here we carry in silico analysis of the molecular effects causing such a difference and reveal the role of individual amino acids. It is shown that the computational modeling correctly predicts experimentally determined pKa’s of histidine residues in an unbound state in the majority of the cases and the pH-dependence of the binding free energy. Structural analysis carried in conjunction with calculated pH-dependence of the binding revealed that …

G13-425 2013 Nebraska Beef Report Summaries, Richard J. Rasby, Karla Jenkins, Galen Erickson

University of Nebraska-Lincoln Extension: Historical Materials

Brief synopsis of recent UNL beef research. Each year the UNL Department of Animal Science reports its current beef cattle research. This 2013 NebGuide discusses the research topics of Cow/Calf, Growing, Finishing and Beef Products.

Analysis Of Free Fractions For Chiral Drugs Using Ultrafast Extraction And Multi-Dimensional High-Performance Affinity Chromatography, Xiwei Zheng, Michelle J. Yoo, David S. Hage

David Hage Publications

A multi-dimensional chromatographic approach was developed to measure the free fractions of drug enantiomers in samples that also contained a binding protein or serum. This method, which combined ultrafast affinity extraction with a chiral stationary phase, was demonstrated using the drug warfarin and the protein human serum albumin.

This report describes a multi-dimensional HPAC system that used ultrafast affinity extraction and chiral chromatography to simultaneously examine the free forms of drug enantiomers in complex samples (e.g., serum) and to study the binding of such drugs with proteins. R/S-Warfarin and its binding protein human serum albumin (HSA) were used as models …

Use Of Entrapment And High-Performance Affinity Chromatography To Compare The Binding Of Drugs And Site-Specific Probes With Normal And Glycated Human Serum Albumin, Abby J. Jackson, Jeanethe Anguizola, Erika L. Pfaunmiller, David S. Hage

David Hage Publications

Protein entrapment and high-performance affinity chromatography were used with zonal elution to examine the changes in binding that occurred for site-specific probes and various sulfonylurea drugs with normal and glycated forms of human serum albumin (HSA). Samples of this protein in a soluble form were physically entrapped within porous silica particles by using glycogen-capped hydrazide-activated silica; these supports were then placed into 1.0 cm × 2.1 mm inner diameter columns. Initial zonal elution studies were performed using (R)-warfarin and L-tryptophan as probes for Sudlow sites I and II (i.e., the major drug binding sites of HSA), giving quantitative measures of …