Physical Sciences and Mathematics Commons^™

Lead Bioaccessibility And Commonly Measured Soil Characteristics (Detroit, Mi, Usa) – Phase 1, Sabrina R. Good, Allison R. Harris, Patrick Crouch, Conor T. Gowan, William D. Shuster, Shawn P. Mcelmurry

Open Data at Wayne State

Contaminated urban soil is one of the major contributors to child Pb exposure. To gain a better understanding of Pb risk in urban areas, composite samples were collected from 142 residential, privately owned, parcels in Detroit, Hamtramck, and Highland Park, Michigan, with approval from the property owners. The proximity of soil sampling and former smelter locations were also reported. Sample were collected from areas covered with turf grass. Four samples were collected, one from each cardinal direction (north, south, east, and west), 20 cm from an aluminum tent stake driven into the center of the sampling site. Soils were collected …

Kinase-Catalyzed Labeling To Identify Kinase-Substrate Pairs Using Γ-Phosphate Modified Atp Analogs, Rachel Beltman

Wayne State University Dissertations

Post-translational modifications (PTMs) are responsible for a variety of cellular processes. One such PTM is protein phosphorylation, which is catalyzed by kinases. Kinase enzymes play important roles in cellular signaling pathways, but dysregulation of kinase-mediated events results in the formation of diseases, which make kinases favorable drug targets. To uncover the role kinases play in the development of diseases, kinase-mediated cellular events need to be better understood. The current gap in the field is the lack of tools available to identify the kinase that is responsible for specific phosphorylation events within the cell. To improve the gap in the field, …

Study Of Zyomogen Granule Movement Along Actin Filaments Using A Single Beam Optical Trap, Justin James Raupp

Wayne State University Dissertations

Zymogen granules are enzymatic vesicles in the pancreas. The surface of these zymogen granules (ZGs) has several different kinds of myosin molecules, such as myosin 1c, 6, 5c, and 7b. These molecular motors may contribute to ZG transportation in cells. To understand the molecular motors involved in the vesicle trafficking, we observed the in vitro motility of purified ZGs from rat pancreas and examined the stepping behavior and force that is generated using a single beam optical trap. To be involved in trafficking, molecular motors have certain characteristics, a high duty ratio and the ability to move continuously along actin …

Rhizobium Symbiotic Capacity Shapes Root-Associated Microbiomes In Soybean, Yuanhui Lu, Bin Ma, Wenfeng Chen, Klaus Schlaeppi, Matthias Erb, Erinne Stirling, Lingfei Hu, Entao Wang, Yunzeng Zhang, Kankan Zhao, Zhijiang Lu, Shudi Ye, Jianming Xu

Environmental Science and Geology Faculty Research Publications

Root-microbiome interactions are of central importance for plant performance and yield. A distinctive feature of legumes is that they engage in symbiosis with N₂-fixing rhizobia. If and how the rhizobial symbiotic capacity modulates root-associated microbiomes are still not yet well understood. We determined root-associated microbiomes of soybean inoculated with wild type (WT) or a noeI mutant of Bradyrhizobium diazoefficiens USDA 110 by amplicon sequencing. UPLC-MS/MS was used to analyze root exudates. The noeI gene is responsible for fucose-methylation of Nod factor secreted by USDA 110 WT strain. Soybean roots inoculated with the noeI mutant showed a significant decrease …

Abhd5 Induced Morphological Changes On Model Membrane Systems, Nasser S. Junedi

Honors College Theses

Proper regulation of neutral lipid storage (lipogenesis) and release (lipolysis) are critical molecular processes localized to an organelle called the Lipid Droplet (LD). The LD consists of a core with neutral lipids such as triacylglycerols (TAGs) and sterol esters surrounded by a phospholipid monolayer. Dysregulation of the processes localized to the LD are involved in the pathology of various diseases such as Neutral Lipid Storage Disease, diabetes, stroke and cancer. The non-enzymatic protein ABHD5 (α-β Hydrolase Domain-Containing Protein 5), is thought to play a key role in the process of lipolysis by forming homo-oligomers on the surface of the LD …

Mite Diet Sequences Obtained By High Throughput Sequencing Of Gut Contents Of Freshly Collected Water Mites, Adrian Amelio Vasquez, Obadeh Mohiddin, Zeyu Li, Brittany L. Bonnici, Katherine Gurdziel, Jeffrey L. Ram

Physiology Faculty Research Publications

Cytochrome oxidase subunit I (COI) barcode sequences in this file were obtained from gut DNA extracted from 54 freshly collected water mites, comprising 21 Lebertia quinquemaculosa , 30 Lebertia davidcooki , 1 Limnesia , and 2 Arrenurus specimens. Methods and other details about these sequences are described in a paper by the same authors in a submitted publication (2021: URL to be given here when published). Data on collection locations, primers (mLep and LCOI), amino acid translations, etc. are included in corresponding sequences uploaded to GenBank. The right column below contains additional notes on naming the taxa of the sequences …

A Framework For Aquatic Invasive Species Surveillance Site Selection And Prioritization In The Us Waters Of The Laurentian Great Lakes, Andrew J. Tucker, W. Lindsay Chadderton, Gust Annis, Alisha D. Davidson, Joel Hoffman, Jon Bossenbroek, Stephen Hensler, Michael Hoff, Erika Jensen, Donna R. Kashian, Sarah Lesage, Timothy Strakosh

Environmental Science and Geology Faculty Research Publications

Risk-based prioritization for early detection monitoring is of utmost importance to prevent and mitigate invasive species impacts and is especially needed for large ecosystems where management resources are not sufficient to survey all locations susceptible to invasion. In this paper we describe a spatially-explicit and quantitative approach for identifying the highest risk sites for aquatic invasive species (AIS) introduction into the United States’ waters of the Laurentian Great Lakes, a vast inland sea with a surface area of 246,049 square km and a shoreline length of 16,431 km. We compiled data from geospatial metrics available across all of the US …

Representation Learning With Autoencoders For Electronic Health Records, Najibesadat Sadatijafarkalaei

Wayne State University Theses

Increasing volume of Electronic Health Records (EHR) in recent years provides great opportunities for data scientists to collaborate on different aspects of healthcare research by applying advanced analytics to these EHR clinical data. A key requirement however

is obtaining meaningful insights from high dimensional, sparse and complex clinical data. Data science approaches typically address this challenge by performing feature learning in order to build more reliable and informative feature representations from clinical data followed by supervised learning. In this research, we propose a predictive modeling approach based on deep feature representations and word embedding techniques. Our method uses different deep …

Nutrition And Health Status Of Hemodialysis Patients In Dhaka, Bangladesh, Tanjina Rahman

Wayne State University Dissertations

Methods to identify patients at risk for End stage renal disease (ESRD) are a high priority in Bangladesh, where kidney transplants/dialysis options are limited and costly. Every year, 35,000 to 40,000 people reach ESRD in Bangladesh, but currently available facilities can hardly accommodate only 9000 to 10,000 new patients with twice weekly dialysis and the remaining 66% have no access to any kind of renal replacement therapy (RRT) in the form of dialysis or transplantation. Nutrition is an important factor in maintaining good health of hemodialysis patients. However, data on nutritional status of Bangladeshi dialysis patients is limited and is …

Development And Application Of Chemical Tools To Identify Kinase-Substrate Interactions, Aparni Kithulgoda Gamage

Wayne State University Dissertations

Post translational modifications regulate a variety of biological processes inside the cell.Protein phosphorylation is one such PTM modification catalyzed by protein kinases, which aid to transfer a signal from one place to another inside the cell. However, irregularities in kinase-mediated signaling are often implicated in many diseases, making kinases effective drug targets. To understand kinase-related disease formation and to discover drugs to treat these diseases, it is crucial to have a clear understanding on kinase-mediated cell signaling networks. A current gap in the kinase biology field is a lack of tools to identify which kinase phosphorylates which protein substrate inside …

A Novel Item-Allocation Procedure For The Three-Form Planned Missing Data Design, Kyle M. Lang, E. Whitney G. Moore, Elizabeth M. Grandfield

Kinesiology, Health and Sport Studies

We propose a new method of constructing questionnaire forms in the three-form planned missing data design (PMDD). The random item allocation (RIA) procedure that we propose promises to dramatically simplify the process of implementing three-form PMDDs without compromising statistical performance. Our method is a stochastic approximation to the currently recommended approach of deterministically spreading a scale's items across the X-, A-, B-, and C-blocks when allocating the items in a three-form design. Direct empirical support for the performance of our method is only available for scales containing at least 12 items, so we also propose a modified approach for use …

Evaluation Of An Educational Campaign To Improve The Conscious Consumption Of Recreationally Caught Fish, Corey A. Krabbenhoft, Susan Manente, Donna R. Kashian

Environmental Science and Geology Faculty Research Publications

Consumption guidelines are a common way of improving conscious consumption behaviors in areas where game fish are known to contain contaminants. However, guideline information can be difficult to distribute, and effectiveness difficult to measure. To increase the distribution and effectiveness of guideline information for the Detroit River, an educational campaign was launched in 2010, which included distribution of pamphlets with consumption information, posting of permanent signs at popular fishing locations, and hiring River Walkers to personally communicate with anglers. In 2013 and 2015, we conducted in-person surveys of active shoreline anglers to determine the effectiveness of education and outreach efforts. …

The Dynamic Nature And Biophysical Characterization Of Isu1, Fe-S Cluster Assembly Scaffold Protein In Saccharomyces Cerevisiae, And Its Significance To Human Disease, Brianne Elizabeth Lewis

Wayne State University Dissertations

Mitochondrial Fe-S cluster biosynthesis is accomplished within yeast utilizing the biophysical characteristics of the “Isu1” scaffold protein. As a member of a highly homologous protein family, Isu1 has sequence conservation with orthologs and a conserved ability to assemble [2Fe-2S] clusters. Regardless of species, scaffold orthologs can exist in both “disordered” and “structured” conformations and is directly related to conformations utilized during Fe-cofactor assembly. During assembly, the scaffold directs the delivery and the utilization of both Fe(II) and sulfide substrates in order to produce [2Fe-2S] clusters, however Zn(II) binding can alter the activity of the scaffold with stabilizing the protein in …

Functional Characterization Of Accessory Proteins And Novel Activities In Direct And Indirect Trna Aminoacylation, Udumbara Menike Rathnayake

Wayne State University Dissertations

Indirect tRNA aminoacylation is essential for most bacteria and archaea, particularly when these species do not have genes encoding asparaginyl- and/or glutaminyl-tRNA synthetase (AsnRS and GlnRS). In the absence of AsnRS, the first step in Asn-tRNAAsn synthesis involves misacylation of tRNAAsn with aspartate to produce Asp-tRNAAsn; this reaction is catalyzed by a non-discriminating aspartyl-tRNA synthetase (ND-AspRS). Subsequently, in bacteria, an amidotransferase called GatCAB converts Asp-tRNAAsn to Asn-tRNAAsn. An analogous, two-step processes exist to produce Gln-tRNAGln. In this case, a non-discriminating glutamyl-tRNA synthetase (ND-GluRS) misacylates tRNAGln to produce Glu-tRNAGln, which is then converted to Gln-tRNAGln by GatCAB. The central hub of …

Of Typicality And Predictive Distributions In Discriminant Function Analysis, Lyle W. Konigsberg, Susan R. Frankenberg

Human Biology Open Access Pre-Prints

While discriminant function analysis is an inherently Bayesian method, researchers attempting to estimate ancestry in human skeletal samples often follow discriminant function analysis with the calculation of frequentist-based typicalities for assigning group membership. Such an approach is problematic in that it fails to account for admixture and for variation in why individuals may be classified as outliers, or non-members of particular groups. This paper presents an argument and methodology for employing a fully Bayesian approach in discriminant function analysis applied to cases of ancestry estimation. The approach requires adding the calculation, or estimation, of predictive distributions as the final step …

Cyanobacteria Reduce Quagga Mussel (Dreissena Rostriformis Bugensis) Spawning And Fertilization Success, Anna G. Boegehold, Nicholas S. Johnson, Jeffrey L. Ram, Donna R. Kashian

Environmental Science and Geology Faculty Research Publications

Quagga mussels (Dreissena rostriformis bugensis) are highly fecund broadcast spawners invasive to freshwaters of North America and western Europe. We hypothesized that environmental cues from phytoplankton can trigger gamete release in quagga mussels. Nutritious algae may stimulate dreissenid spawning, but less palatable food, such as bloom-forming cyanobacteria, could be a hindrance. The objective of our study was to test whether exposure to cyanobacteria can inhibit quagga mussel spawning and fertilization. We assessed spawning in the presence of serotonin, a known spawning inducer, where adult quagga mussels placed in individual vials were exposed to 13 cyanobacteria cultures and purified algal toxin …

Functional Study Of Smyd2 Glutathionylation In Cardiomyocytes, Dhanushka Nalin Perera Munkanatta Godage

Wayne State University Dissertations

Reactive oxygen species (ROS) are important signaling molecules that contribute to the etiology of multiple muscle-related diseases, including cardiomyopathy and heart failure. There is emerging evidence that cellular stress can lead to destabilization of sarcomeres, the contractile unit of muscle. However, it is not completely understood how cellular stress or ROS induce structural destabilization of sarcomeres or myofibrils. Protein glutathionylation is one of the major protein cysteine oxidative modifications that play an important role in redox signaling and oxidative stress. In this report, we used a clickable glutathione approach in a cardiomyocyte cell line, and found that SET and MYND …

Polarized Localization Microscopy (Plm) Detects Nanoscale Membrane Curvature And Induced Budding By Cholera Toxin Subunit B (Ctxb), Abir Kabbani

Wayne State University Dissertations

The curvature of biological membranes at the nanometer scale is critically important for vesicle trafficking, organelle morphology, and disease propagation. Many proteins and lipids interact with diverse curvature sensing and curvature generating mechanisms. Deciphering the molecular mechanisms of toxin-membrane interactions has been limited by the resolution and drawbacks of conventional experimental techniques. This study reveals the inherent membrane bending capability of cholera toxin subunit B (CTxB) through the development and implementation of Polarized Localization Microscopy (PLM). PLM is a pointillist optical imaging technique for the detection of nanoscale membrane curvature in correlation with single-molecule dynamics and molecular sorting.

PLM combines …

Carbazole Based Multifunctional Dopamine Agonists And Related Molecules As Potential Symptomatic And Disease Modifying Therapeutic Agents For Parkinson’S Disease, Asma S.Mohamed Elmabruk

Wayne State University Dissertations

Parkinson’s disease (PD) is a progressive neurodegenerative disease that develops from gradual depletion of dopamine (DA) and dopaminergic neurons in the substantia nigra pars compacta (SNc) with the accumulation of intraneuronal proteinaceous matter named as Lewy bodies. The four cardinal symptoms associated with PD are tremor, rigidity, bradykinesia, and postural instability. Although the exact mechanism and etiology of PD are not fully understood, several factors have been implicated in the pathogenesis and progression of PD including protein aggregation, oxidative stress, mitochondrial dysfunction, environmental, and genetic factors.

The current therapy of Parkinson’s disease is categorized into four classes: levodopa, DA agonists, …

Carbohydrate-Based Inducers Of Cellular Stress For Targeting Cancer Cell Metabolism, Fidelis Ndombera

Wayne State University Dissertations

ABSTRACT

CARBOHYDRATE-BASED INDUCERS OF CELLULAR STRESS FOR TARGETING CANCER CELL METABOLISM

by

FIDELIS TOLOYI NDOMBERA

May 2018

Advisor: Dr. Young-Hoon Ahn

Major: Chemistry (Biochemistry)

Degree: Doctor of Philosophy

Metabolic reprogramming and redox control of cancer cells is vital for their proliferation, but also provides selective strategies for treating cancer. Increased generation of reactive oxygen species (ROS) and an intricate control of redox status in cancer cells relative to normal cells provide a basis for designing ROS-inducing anticancer agents. In my work, I designed, synthesized and evaluated carbohydrate-based small molecules for ROS-generation, cytotoxicity and redox signaling and stress response. Our data …

Drug Delivery Strategies For The Treatment Of Advanced Lung Cancer And Various Lung Metastases, Elizabeth Bielski

Wayne State University Dissertations

Lung cancer remains the leading cause of cancer-related deaths in the United States. Secondary lung tumors metastasized from other cancer sites also remains highly prevalent, in which most metastatic tumors cannot be cured with existing therapies. Chemoresistance (multi drug resistance – MDR) that develops intrinsically or acquired is one of the key factors leading to fatality in these patients. MDR develops form a variety of resistance mechanisms that can occur consecutively or concurrently, therefore, making most current treatments unsuccessful. Current therapies have known to slow tumor growth, but rarely provide a cure. Immunotherapy has seen some promise, including the use …

Design, Synthesis, And Reactivity Of Homo- And Heterobimetallic Complexes Bridged By A Xanthene Linker, Thilini Samangi Hollingsworth

Wayne State University Dissertations

Cooperative reactivity of bimettalics can be is observed in many different areas of chemistry and have been increasingly investigated because of the advantageous reactivity when compared to the corresponding mononuclear systems. The focus of my dissertation is on (1) investigation of the homobimetallic cooperativity in lactide polymerization catalysis; (2) investigation of the heterobimetallic cooperativity in the biomimetic studies of Mo-Cu carbon monoxide dehydrogenase (CODH) enzyme in order to make a functional model of its active site.

Three new main group bis(alkoxide) complexes Mg(OR)2(THF)2, Zn(Cl)(μ2-OR)2Li(THF) and In(OR)2(μ2-Cl)2Li(THF)2 featuring bulky alkoxide [OCtBu2Ph] were synthesized serve as metal alkoxide precursors for bimetallic lactide …

Qualitative Change Detection Approach For Preventive Therapies, Cristina Mitrea

Wayne State University Dissertations

Currently, most diseases are diagnosed only after disease-associated changes have occurred. In this PhD dissertation, we propose a paradigm shift from treating the disease to maintaining the healthy state. The proposed approach is able to identify when systemic qualitative changes in biological systems happen, thus opening the possibility of therapeutic interventions before the occurrence of symptoms. The change detection method exploits knowledge from biological networks and longitudinal data using a system impact analysis approach. This approach is validated on eight datasets, for seven different model organisms and eight biological phenomena. On these data, our proposed method performs well, consistently identifying …

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 …

The Development Of Chemical Methods To Discover Kinase Substrates And Map Cell Signaling With Gamma-Modified Atp Analog-Dependent Kinase-Catalyzed Phosphorylation, Dissanayaka Mudiyanselage Maheeka Madhubashini Embogama

Wayne State University Dissertations

Kinase-catalyzed phosphorylation plays an important role in cell physiology by regulating a myriad of cellular functions. Thus aberrant kinase activity is implicated in various diseases. Methods are needed to discover kinase substrates and map signaling pathways to explore biology and to help drug discovery. A few techniques are currently available to discover kinase substrate and map cell signaling. However, to augment kinase substrate discovery approaches, it is essential to develop alternative techniques. Pflum has recently discovered cosubstrate promiscuity of protein kinases with gamma-modified ATP analogs. Here, kinase-catalyzed biotinylation with ATP-biotin was used to develop novel tools to discover kinase substrates …

Structural Basis Of Membrane Protein Scaffolding And Signaling In Human Disease, Joshua Holcomb

Wayne State University Dissertations

Protein structural elucidation by means of X-ray crystallography is a powerful approach for both insight into a proteins biophysical properties and function. To date X-ray crystallography remains the gold standard in high resolution structural determination and serves as the basis for rational drug design for the purpose of combating a number of human diseases. Such an approach also allows for the exploitation of how various proteins interact with their substrates providing a molecular basis for their physiological function. In this dissertation, using X-ray crystallographic analysis along with other biophysical characterization methods, we seek to understand the mechanistic foundation for which …

Design, Synthesis And Biological Evaluation Of Histone Deacetylase (Hdac) Inhibitors: Saha (Vorinostat) Analogs And Biaryl Indolyl Benzamide Inhibitors Display Isoform Selectivity, Ahmed Negmeldin

Wayne State University Dissertations

HDAC proteins have emerged as interesting targets for anti-cancer drugs due to their involvement in cancers, as well as several other diseases. Several HDAC inhibitors have been approved by the FDA as anti-cancer drugs, including SAHA (suberoylanilide hydroxamic acid, Vorinostat). Unfortunately, SAHA inhibits most HDAC isoforms, which limit its use as a pharmacological tool and may lead to side effects in the clinic. In this work we were interested in developing isoform selective HDAC inhibitors, which may decrease or eliminate the side effects associated with non-selective inhibitors treatment. In addition, isoform selective HDAC inhibitors can be used as biological tools …

Development Of Chemical Tools To Investigate Protein S-Glutathionylation In Response To Metabolic Alteration, Kusal Theekshana Gayan Samarasinghe

Wayne State University Dissertations

Oxidative stress is a common characteristic of age-related diseases such as vascular diseases, diabetes and cancer. Many diseases are known to be regulated by glutathionylation. Glutathionylation is referred to as the formation of disulfide bond between a protein cysteine and a glutathione. To understand the molecular mechanisms behind the disease initiation and progression, identification of such glutathionylated proteins is important. Even though existing methods have been widely used, several limitations of these methods hinder the identification of such proteins in disease conditions. Therefore, we developed a versatile chemical method that generates clickable glutathione inside the cells. In this method, we …

The In Vivo Effect Of Oil Palm Phenolics (Opp) In Atherogenic Diet Induced Rats Model Of Alzheimer’S Disease (Ad), Yan Wu

Wayne State University Dissertations

Alzheimer’s disease (AD) is the most common cause of dementia in the aging population. It is characterized by cognitive decline and deposition of ß-amyloid plaques in the hippocampus. It has been shown that hypercholesterolemia induced by high cholesterol diet is associated with AD development. Increased level of oxidative stress has also been observed in AD patients. An important strategy to treat or delay the impairment is based on dietary modification, using food supplements. OPP, a water soluble fraction from oil palm fruit, rich in phenolics has been found to possess significant antioxidant activities. Its beneficial effects on cardiovascular diseases, diabetes …