Life Sciences Commons^™

Development Of An Automated Detection System For Nitrite In Aquatic Environments, Tim Schierenbeck

Theses and Dissertations

The main objective of the project is to develop an automated nitrite sensor for use in aquatic environments, and more specifically for use in recirculating aquaculture systems (RAS), where monitoring can help sustain a controlled environment, protect against nitrite intoxication, and promote fish health. Detecting nitrite manually with semi-quantitative colorimetric test kits, although inexpensive and simple, is prone to inter-user variability and poor sensitivity. An automated nitrite sensor has potential to provide higher resolution measurements at both concentration and time scales and can serve as a research tool for the study of filtration systems essential in maintaining a healthy RAS …

The Role Of Proteome In Cellular Zn2+ Trafficking And In The Ability Of The Fluorescent Zinc Sensors To Image Intracellular Zn2+, Mohammad Rezaul Karim

Theses and Dissertations

Zinc is an essential biological trace metal used in as many as 3000 Zn-proteins, about 10% of the eukaryotic proteome, as either a structural constituent or a catalytic cofactor. These proteins include the zinc fingers, the most prevalent transcription factors that bind a wide range of gene promoters and thus regulate gene expression. A eukaryotic cell contains several hundred micromolar of Zn2+- almost all of it is bound to specific Zn-proteins. Recently, Zn2+ has been reported to serve as a regulatory signal and a neurotransmitter, suggesting that there also exists a dynamic Zn2+ pool in cells. These findings led to …

Structural And Functional Characterization Of Acetoacetate Decarboxylase-Like Enzymes, Lisa Mueller

Theses and Dissertations

The acetatoacetate decarboxylase-like superfamily (ADCSF) is a largely unexplored group of enzymes that may be a potential source of new biocatalysts. Bioinformatic analysis has grouped these approximately 2000 enzymes into seven different families based on comparison of predicted active site residues. To date, only the prototypical ADCs (Family I) that catalyze the decarboxylation of acetoacetate have been studied. Analysis of gene context suggests that Family V contains predominantly enzymes predicted to be involved in secondary metabolism. On average, these share about 20% sequence identity to the true ADCs. To learn more about the diversity of chemistries performed by members of …

Development Of Cellular High Throughput Assays To Determine The Electrophysiological Profile Of Gaba(A) Receptor Modulators For Neurology And Immunology, Nina Yina Yuan

Theses and Dissertations

Gamma (γ) -aminobutyric acid (GABA) is the major inhibitory neurotransmitter found in

the mammalian central nervous system. Its effect stems from its ability to cause the opening of ion channels which causes an influx of negatively charged chloride ions or an efflux of positively charged potassium ions. This hyperpolarization of the neuron lowers the threshold for neuronal firing. This has an overall inhibitory effect on neurotransmission, decreasing the excitability of the neuron and diminishing the likelihood of a successful action potential occurring. There are two classes of GABA receptor: ligand-gated GABAA receptor (GABAAR) and metabotropic GABAB receptor (GABABR). The GABAAR …

The Function Of Renalase, Brett Allen Beaupre

Theses and Dissertations

Renalase was originally reported to be an enzyme secreted into the blood by the kidney to lower blood pressure and slow heart rate. Despite multiple reports claiming to confirm this activity in vivo there has been considerable discord in regards to the reaction catalyzed by renalase. The structural topology of renalase resembles that of known flavoprotein oxidases, monooxygenases and demethylases, but the conserved active site residues are unique to renalase. It has been reported that the catalytic function of renalase is to oxidize circulating catecholamines, however in vitro studies have failed to demonstrate a catalytic activity in the presence of …

Synthesis And Biological Activity Of Novel Quorum Sensing Compounds, Joseph Nicholas Capilato

Theses and Dissertations

Bacteria communicate with chemical signals in a process known as quorum sensing. This population density-dependent process involves the bacterial production, release and detection of structurally specific small molecules and enables the bacterial pathogen to regulate its virulence on a population-wide level. Using a variety of chemical and biological techniques, I have studied various quorum sensing systems in several bacteria, including Vibrio cholera and Pseudomonas aeruginosa. A key principle of this research involves the design, synthesis and testing of novel compounds for their biological activity. These molecules are typically based off of an initial lead target, which is often identified …

Inhibitory Effects Of Unique Sulfonamides On Leishmania Tarentolae And Potential Pathway Of Inhibition, Jade M. Katinas

Theses and Dissertations

Leishmaniasis is an endemic disease caused by the protozoan parasite Leishmania. Current treatments for the parasite are limited by cost, availability, and drug resistance as the worldwide occurrence of leishmaniasis continues to be more prevalent. Sulfonamides are a class of compounds with medicinal properties that have been used to treat bacterial and parasitic diseases via various pathways. In this study, newly synthesized, unique structural analogs of sulfonamide compounds were assessed for their impact on Leishmania cell viability and potential pathways for inhibition were evaluated. Leishmania tarentolae (ATCC Strain 30143) axenic promastigote cells were grown in BHI medium and treated with …

Placental ‘€˜Omics’€™ Study To Understand The Pathogenesis Of Preeclampsia, Komal Kedia

Theses and Dissertations

Preeclampsia (PE) is a potentially fatal complication of pregnancy characterized by an increase in blood pressure (>140/90 mmHg) and proteinuria (>300 mg/24 hrs), often accompanied by edema. Symptoms of PE start after 20 weeks of gestation. If PE remains untreated, it can lead to eclampsia, grand-mal seizures responsible for most fatalities. PE is believed to affect 2-10% of pregnancies worldwide, and claims the lives of over 75,000 mothers and 500,000 newborns yearly. No therapeutic agents have been developed to prevent or cure PE. Part of the reason for this is the absence of a complete understanding of the …

14-3-3Ζ Regulation Of Metastasis Through Mediation Of Liprin-Α And Liprin-Β, Rachel Hynes

Theses and Dissertations

Cancer is a set of varied and diverse diseases that share common characteristics, such as active proliferation, increased replicative potential, and tissue invasion or metastasis. One protein, 14-3-3ζ, is shown to be upregulated in a number of different cancers and also correlates with poor patient prognosis, recurrence, and mortality. This protein comes from a family of adapter proteins known for their scaffolding ability, pro- and anti-oncogenic capabilities, and affinity for phosphorylated substrates. It has been shown previously to participate in cancer progression, subversion of apoptosis, and to increase chemoresistance. Herein we will discuss the ability of 14-3-3ζ to promote distant-site …

Development And Application Of New Solid-State Models For Low-Energy Vibrations, Lattice Defects, Entropies Of Mixing, And Magnetic Properties, Jacob M. Schliesser

Theses and Dissertations

Low-temperature heat capacity data contain information on the physical properties of materials, and new models continue to be developed to aid in the analysis and interpretation of heat capacity data into physically meaningful properties. This work presents the development of two such models and their application to real material systems. Equations describing low-energy vibrational modes with a gap in the density of states (DOS) have been derived and tested on several material systems with known gaps in the DOS, and the origins of such gaps in the DOS are presented. Lattice vacancies have been shown to produce a two-level system …

Probing Allosteric, Partial Inhibition Of Thrombin Using Novel Anticoagulants, Stephen S. Verespy Iii

Theses and Dissertations

Thrombin is the key protease that regulates hemostasis; the delicate balance between procoagulation and anticoagulation of blood. In clotting disorders, like deep vein thrombosis or pulmonary embolism, procoagulation is up-regulated, but propagation of clotting can be inhibited with drugs targeting the proteases involved, like thrombin. Such drugs however, have serious side effects (e.g., excessive bleeding) and some require monitoring during the course of treatment. The reason for these side effects is the mechanism by which the drugs’ act. The two major mechanisms are direct orthosteric and indirect allosteric inhibition, which will completely abolish the protease’s activity. Herein we sought an …