Life Sciences Commons^™

Mitochondrial Roles In Developmentally Programmed Heart Disease, Eli John Louwagie

Dissertations and Theses

Offspring of diabetic and obese mothers (ODOM) have greater risks of heart disease at birth and later in life. However, prevention is hindered because underlying mechanisms are poorly understood. Mounting studies in the Developmental Origins of Health and Disease field suggest that mitochondria play key roles in developmentally programmed heart disease similar to the roles they play in cardiomyopathy in adults with diabetes and obesity. However, whether mitochondria are responsible for the short[1]and long-term cardiac disease seen in ODOM remains unknown. Here, we sought to delineate the roles of mitochondria in the hearts of ODOM, determine whether mitochondria ...

Determining The Full-Length Structure Of Collagenase H Using Small-Angle X-Ray Scattering, Josie Carson

Chemistry & Biochemistry Undergraduate Honors Theses

Known to cause gas gangrene, Hathewaya histolytica secretes two sister collagenases, collagenase G (Col G) and collagenase H (Col H), to degrade the triple helical structure of collagen to further infection in a host. Individual domains of Col H have been crystalized in previous studies, but methods in x-ray crystallization of full-length Col H have been unsuccessful. Using Small Angle X-Ray Scattering (SAXS) data, atomistic modeling was used to generate multiple conformations of Col H while accounting for flexibility between domains. Full-length Col H was found to adopt a two-state conformational model exhibiting a majority compact and a minority elongated ...

Molecular Mechanism Of Rapamycin Resistance In Cancer Cells, Sohag Chakraborty

Dissertations, Theses, and Capstone Projects

The mammalian target of rapamycin (mTOR) acts as the central regulator of multiple cellular processes including cell growth, proliferation, and survival by integrating signals via nutrients, growth factors, hormones, and energy sensing. In cancer cells, the mTOR pathway is highly dysregulated providing survival signals to the cells for their uncontrolled growth. Hence, mTOR has evolved to be a potential therapeutic target for cancer treatment for the past two decades. Application of micro-molar doses of Rapamycin in vitro has been found to successfully inhibit mTOR complex 1 (mTORC1) by blocking the phosphorylation of its downstream substrates- a) ribosomal protein p70 S6 ...

Flippase Inhibitors As Antimicrobial Agents, Robert Tancer

Seton Hall University Dissertations and Theses (ETDs)

Drug resistant microbes are a considerable challenge for modern medicine to overcome. The research described in this dissertation involved development of lipid flippase inhibitors and investigating their potential as antimicrobial agents against various drug resistant microbes. The microbes primarily investigated were methicillin resistant Staphylococcus aureus (MRSA) & Cryptococcus neoformans. Chapter 1 reviews the historical perspective and summarizes the current state of the field of research. In Chapter 2, the design space of an antimicrobial peptide known as humimycin was explored and the effects of modifications on its structure were observed against MRSA. Several key observations resulted. Most notably, the nanoparticles formed ...

Science, Physiology, And Nutrition For The Nonscientist, Judi S. Morrill

Open Educational Resources

A wonderful blend of physiology, nutrition, biochemistry, genetics, biology, evolution, chemistry--what we all need to know as informed citizens. A basic knowledge of the life sciences and how our bodies work--to promote our own good health, especially as we're bombarded with misleading advertisements, soundbites, and the like. DNA fingerprinting, calorie requirements, dietary advice, genetic engineering (including gene editing with CRISPR cas9)--all in an easy-to understand book.

G Protein–Coupled Receptor 21 In Macrophages: An In Vitro Study, Valentina Bordano, Gemma K. Kinsella, Stefania Cannito, Chiara Dianzani, Casimiro Luca Gigliotti, John C. Stephens, Chiara Monge, Claudia Bocca, Arianna C. Rosa, Gianluca Miglio, Umberto Dianzani, John B.C. Findlay, Elisa Benetti

Articles

GPR21 is an orphan and constitutively active receptor belonging to the superfamily of G-Protein Coupled Receptors (GPCRs). GPR21 couples to the Gq family of G proteins and is markedly expressed in macrophages. Studies of GPR21 knock-out mice indicated that GPR21 may be involved in promoting macrophage migration. The aim of this study was to evaluate the role of GPR21 in human macrophages, analyzing (i) its involvement in cell migration and cytokine release and (ii) the consequence of its pharmacological inhibition by using the inverse agonist GRA2. THP-1 cells were activated and differentiated into either M1 or M2 macrophages. GPR21 expression ...

The Use Of Nebulizer Medications As A Possible Treatment For Covid-19, Jacob Kaufman

Honors College Theses

For the past few years, the COVID-19 pandemic has been the focal point in healthcare and research. This disease has permanently changed daily life and left a historic impact on the world. Most people have felt the effects of this pandemic either directly, via infection, or indirectly, via change in workflow, financial impact, etc. The main question for this virus still remains today; how do we treat this illness effectively? While many ideas are being tested and suggested, a definite answer has yet to be procured. Vaccine rates are climbing on a daily basis, serving as the first and most ...

Synthesis, Structural Characterization, And In Vitro Biological Assessment Of Trans- Platinum (Ii) Thionate Complexes As Potent Anticancer Agents, Mia Alshami

Chemistry & Biochemistry Undergraduate Honors Theses

The content of this thesis has been originally reported in our published paper, “trans-Platinum (II) Thionate Complexes: Synthesis, Structural Characterization, and in vitro Biological Assessment as Potent Anticancer Agents” ChemPlusChem 2019 84, 1525-1535, DOI: 10.1002/cplu.201900394, in which I served as coauthor. Cancer caused 9.6 million deaths in 2018 worldwide, with 18.1 million new diagnoses during that same year.The most widely used metal in anticancer drugs is platinum (Pt), and these drugs are used to treat almost 50% of cancer patients. To optimize drug effectiveness, trans-configured Pt(II) complexes have been introduced as ...

Characterization Of Fgf1/Fgf2 Heterodimer With Mutation R136e, Brett Haley

Biological Sciences Undergraduate Honors Theses

Fibroblast growth factors are a family of heparin binding proteins that are involved in a broad spectrum of physiological functions, such as angiogenesis, cell proliferation, cell differentiation, and wound healing. Fibroblast growth factor 1 (FGF-1) is a member of the FGF superfamily and can bind universally to fibroblast growth factor receptors. Fibroblast growth factor 2 (FGF-2) is similar in structure to FGF-1 but has been shown to have a potent effect on angiogenesis. A physiologically stable dimerization of these two growth factors could prove to induce desirable effects in the instance of wound healing. In this study, we have designed ...

Regulation Of The Reaction Between Cytochrome C And Cytochrome C Oxidase In The Mitochondria, Anders Nowell

Biological Sciences Undergraduate Honors Theses

Cytochrome c (Cc) is a multifunction protein that has important life and death functions in the cell. In the electron transport chain (ETC), Cc transfers electrons from cytochrome bc₁ to cytochrome c oxidase (CcO), which helps build the electrochemical gradient that drives ATP synthase. The reaction of Cc with CcO is very important in ETC regulatory processes. Previous research shows phosphorylation sites in Cc that affect the binding with CcO, with measurable effects on k_d, k_f, and K_D. These effects result in changes in mitochondrial membrane potentials, respiration, and reactive oxygen species (ROS) scavenging. This research ...

Characterization Of A Protein-Small Molecule Interaction Between Microtubules And Novel Ruthenium-Polypyridyl Complexes, Chloe Hutchison

Chemistry & Biochemistry Undergraduate Honors Theses

Microtubules are cytoskeletal filaments that play a role in essential functions within the cell such as cell motility, intracellular transport, structural support and chromosome segregation. Tubulin is a heterodimeric protein that exhibits GTP dependent polymerization and self- assembles into polar microtubule filaments. Microtubules are dynamic polymers corresponding to their role in separation of duplicated chromosomes during mitosis. As the polymers cycle through rounds of polymerization and depolymerization based on their nucleotide state, the chromosomes are pulled towards the poles in the mitotic cell. Their normal function and dynamics can be disrupted in highly proliferative cells that interrupt cell cycle progression ...

Studying The Lysine Acetylation Of Aconitase Isozymes In E. Coli, Sara Ottinger

Chemistry & Biochemistry Undergraduate Honors Theses

The contents of this thesis have been modified from the publication “Araujo J, Ottinger S, Venkat S, Gan Q and Fan C (2022) Studying Acetylation of Aconitase Isozymes by Genetic Code Expansion. Front. Chem. 10:862483”. Though studies have found multiple lysine sites in which acetylation takes place in Escherichia Coli aconitase, acetylation’s effects on the enzyme’s activity have yet to be studied. Aconitase is the dehydratase-hydratase found in the citric acid and glyoxylate cycles responsible for the reversible isomerization of citrate to isocitrate via cis-aconitate intermediate. There are two isoforms of aconitase in E. coli: AcnA and ...

Severe Hypoxia Up-Regulates Gluconeogenesis In Daphnia, Morad C. Malek

Undergraduate Honors Theses

Hypoxia is a significant low oxygen state that has complex and diverse impacts on organisms. In aerobes, hypoxia causes numerous physiological changes and adaptive responses that vary depending on the level of oxygen depletion and on previous adaptation, hence its continued attention as an important abiotic stressor. Adaptive responses to hypoxia are primarily governed by the hypoxia-inducible-factors (HIFs), which activate downstream genetic pathways responsible for metabolic adjustments and homeostasis maintenance. In aquatic organisms, hypoxia is an important ecological constraint, as oxygen availability within waterbodies can vary greatly over time and space. Therefore, adaptation to hypoxia is likely pervasive, especially in ...

Design, Synthesis, And Analysis Of Paired Coiled-Coil Peptidic Molecular Building Blocks Used For Linearly Controlled Self-Assembly Of Α-Helical Coiled-Coil Heterodimer Peptide Pairs, Jason Distefano

Chemistry Theses

Molecular building blocks are fundamental to biological synthesis and processes and have been utilized in advanced materials, drugs and drug delivery systems, and biotechnology. Proteins have been used as molecular building blocks for the construction of complex, well-ordered structures. Coiled-coil protein domains are essential subunits used for the oligomerization of protein complexes, gene expression, and structural elements of biological materials. The synthesis and assembly of proteins utilizing coiled-coil motifs are of great scientific interest due to their potential applications in disease treatment, biomechanical motors, nanoscale delivery systems, etc. However, assembling protein complexes with specific morphology is still challenging because the ...

Investigation Of Cotinine Concentration Found In Saliva Of Smokers And Vapers In Demographic Sectors, Seth A. Sims

Honors Theses

A simple and reproducible method for investigation of cotinine and nicotine levels in saliva was developed by utilizing gas chromatography mass spectrometry (GCMS) and simple extraction techniques. This method allowed for accurate detection of cotinine in saliva samples collected within a 50-mile radius of Searcy, AR. The observed cotinine levels proportionately depict nicotine levels, which were then compared with participants’ demographics, displaying trends among different communities. This research hopes to provide insight into vaping popularity as well as a reproducible method that future research can utilize.

Evaluating Alternative Ebullition Models For Predicting Peatland Methane Emission And Its Pathways Via Data–Model Fusion, Shuang Ma, Lifen Jiang, Rachel M. Wilson, Jeff P. Chanton, Scott Bridgham, Shuli Niu, Colleen M. Iversen, Avni Malhotra, Jiang Jiang, Xingjie Lu, Jason Keller, Xiaofeng Xu, Daniel M. Ricciuto, Paul J. Hanson, Yiqi Luo

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Understanding the dynamics of peatland methane (CH₄) emissions and quantifying sources of uncertainty in estimating peatland CH₄ emissions are critical for mitigating climate change. The relative contributions of CH₄ emission pathways through ebullition, plant-mediated transport, and diffusion, together with their different transport rates and vulnerability to oxidation, determine the quantity of CH₄ to be oxidized before leaving the soil. Notwithstanding their importance, the relative contributions of the emission pathways are highly uncertain. In particular, the ebullition process is more uncertain and can lead to large uncertainties in modeled CH₄ emissions. To improve model simulations of ...

Using Integrated Rate Equations To Analyze Acid Phosphatase Kinetics, Melissa Gouge

ONU Student Research Colloquium

In an academic setting, enzyme kinetics are introduced by analysis of the initial rates using the Michaelis-Menten model. To better understand enzyme kinetics, a complete time course analysis will provide a larger set of data, including information on feedback or product inhibition. With this, the Lambert W function can be used to analyze the integrated rate equations. We have started our analysis with the enzyme, acid phosphatase. Inorganic phosphorus is a known competitive inhibitor of the acid phosphatase catalyzed hydrolysis of p-nitrophenylphosphate. Using the integrated form of the rate equation allows us to determine the relative relationship of the K ...

Protein Engineering Of A Spectroscopic Probe Into Malate Dehydrogenase (Mdh), Equoia S. Gibson, Mary E. Ludwig, Olivia H. Thompson, Genevieve M. Woods, Ella M. Young

Celebrating Scholarship and Creativity Day

Malate dehydrogenase (MDH) is an enzyme that has a key role in biological processes, like the Krebs cycle. Specifically, it reversibly catalyzes the interconversion of (S)-malate with NAD+ to oxaloacetate and NADH. Once oxaloacetate is synthesized, MDH dispatches it to citrate synthase, but it is not clear how this happens. One theory is that MDH channels it to citrate synthase by forming a metabolon, a mechanism for direct channeling, preventing diffusion of reaction intermediates into a bulk matrix. There is a lack of research in this area due to the absence of a spectroscopic probe necessary to visualize MDH ...

Investigation Of The Role Of Overexpression Of Psbs Under Stress Inducible And Constitutive Promoters To Improve Water Use Efficiency., Annie Nelson

Honors Theses, University of Nebraska-Lincoln

As climate change continues to impact environmental growth conditions, it has become increasingly more important to identify potential mechanisms of crop development to resist these changes. Previous studies have identified the role of PsbS in the non-photochemical quenching (NPQ) mechanism in the plant by identifying its direct effect on the rate in which excitation energy absorbed by photosystem II is dissipated as heat. It was identified also that PsbS via NPQ oxidizes chloroplastic quinone A (QA) which is a signal for stomatal opening in response to light. By identifying this relationship between PsbS and the signal for stomatal opening in ...

Bomb Calorimetry: A New Method Of Cec Determination, Trace Washburn

Undergraduate Research Conference

A new method of determining the cation exchange capacity (CEC) of clay minerals was examined. This method involved exchanging the smectite clay with organic cations and using bomb calorimetry to measure the energy of combustion of the material. Because the clay is noncombustible, the energy is completely dependent on the amount of organic present, which is dependent on the CEC of the clay. Two organic cations, tetrapentylammonium and octadecyltrimethylammonium , with similar size but much different shape were used. For clays with lower CECs, using the more symmetric ion yielded better accuracy (4.24%), while for clays with higher CEC, using ...

Quantification Of Kaempferol Conjugates In Watercress Juice And Methanol Extract: A Study Using Hplc And Protein Binding, Laken Simington

Undergraduate Research Conference

Flavonoids are a large group of biologically active polyphenolic compounds found in plants, that have gained importance in recent years due to their potential medicinal and therapeutic properties of high potency and low systemic toxicity. Kaempferol (3,4′,5,7- tetrahydroxyflavone) is a polyphenol antioxidant dietary flavonoid found in a variety of fruits and leafy vegetables, specifically vegetables of the Brassica family, which includes our subject vegetable, watercress (WC) which is usually grown in marshy lands. Kaempferol (KMP) has been depicted to have revolutionary attribute in overall human health ranging from anti-cancerous to anti-inflammatory properties. Here we show a novel ...

Modelling, Cloning, And Expression Of The J Domain Of C. Elegans Rme-8 Protein, Madison Thornhill, My Tran, Bingbing Xiao

Undergraduate Research Conference

Rme-8 is a J domain containing plasma membrane protein that is required for endocytosis in various cells The J domain is a characteristic structural motif found mainly in heat shock protein 40 (Hsp 40 or DnaJ) and other proteins such as Rme-8 Within the J domain is a tripeptide, the HPD motif, that is required by the J domain protein to interact with and stimulate the ATPase activity of Hsp70 a major cellular chaperone Rme-8 protein in C elegans CeRme-8 has not been identified with a particular Hsp70 partner CeHsp70 1 is the only cytosolic Hsp70 in C elegans therefore ...

Datadescription-Detection Of Sulfur Dioxide By Broadband Cavity-Enhanced Absorption Spectroscopy (Bbceas), Ryan Thalman, Nitish Bhardwaj, Callum Flowerday, Jaron C. Hansen

ScholarsArchive Data

Files archived include the following:

Figure1.txt This file contains all the data used to make Figure 1 in the paper.

Figure4.txt This file contains all the data used to make Figure 4 in the paper.

Figure5.txt This file contains all the data used to make Figure 5 in the paper.

Figure6.txt This file contains all the data used to make Figure 6 in the paper.

Figure7.txt This file contains the code, written in Igor, that was used to generate this figure.

Figure8.txt This file contains all the data used to make Figure 8 in ...

Proline To Serine Mutation In The Active Site Loop Of Malate Dehydrogenase Alters Substrate Specificity, Olivia J. Schmitt

Chemistry & Biochemistry Student Scholarship

Cancer cells preferentially undergo glycolysis in aerobic environments, a phenomenon termed the Warburg effect. Malate dehydrogenase (MDH) catalyzes the reversible interconversion of malate and oxaloacetate. Human cytosolic malate dehydrogenase (hMDH1) isoform 3 is involved in the malate-aspartate shuttle (MAS), which oxidizes cytosolic NADH. hMDH1 is implicated in high aerobic glycolysis in cancer cells because NAD is a necessary cofactor for glycolysis. Thus, hMDH1 is a promising molecular target for cancer treatment. A single proline residue at position 110 in the mobile active site loop of hMDH1 was mutated to a serine with the intention of altering the enzyme’s substrate ...

Development And Kinetic Survey Of A G148t Mutant Human Cytosolic Malate Dehydrogenase Isoform 3 Enzyme With Oxaloacetate And A-Ketoglutarate, Ethan N. Dionne

Chemistry & Biochemistry Student Scholarship

Cancer cells often use an altered metabolic pathway in which glycolysis, uncoupled from the citric acid cycle, serves as the primary source of ATP. To support cancer cell proliferation and growth, the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) must have a constant source of NAD. While lactate dehydrogenase (LDH) in its conversion of pyruvate to lactate is a well-known source of cytosolic NAD for GAPDH activity, cytosolic malate dehydrogenase (MDH1) also plays a role in cell proliferation through its generation of cytosolic NAD by the conversion of OAA to malate. This development has implicated MDH1 in cancer cell metabolism and characterizing ...

Investigation Of Magnesium Cation-Proton Exchange With Transmembrane Electrostatically Localized Protons (Telp) At A Liquid-Membrane Interface: Fundamental To Bioenergetics, Gyanendra Kharel, Andrew J. Evans, Christopher M. Russo, Michael Eason, James W. Lee

College of Sciences Posters

The Lee transmembrane electrostatic proton localization (TELP) theory is a revolutionary scientific theory that has successfully explained decades long-standing quandary in the field of bioenergetics in regards to ATP synthesis in biological systems, specifically alkalophilic bacteria. This study provides experimental support for the TELP theory by further demonstrating evidence of a localized proton layer existing at the liquid-membrane interface in a simulated biological membrane apparatus. Whilst monovalent cations have been studied extensively, divalent cation exchange has not been studied experimentally.

A previous study determined equilibrium constant for Na⁺ and K⁺ to exchange with localized H⁺ layer to be (5.07 ...

Generating A Colorimetric Ssa4 Transcript Export Reporter For Multicopy Suppression Screen In S. Cerevisiae, Zaid Hatem

Belmont University Research Symposium (BURS)

The export of mRNA from the nucleus to the cytoplasm is a regulatory point that is essential to the pathway of gene expression in eukaryotic cells. The export of mRNA transcripts is mediated through selective doorways called the nuclear pore complexes (NPC). Additionally, there are proteins associated with the nuclear pore complex that assist in facilitating the export. This includes association with the export receptor, Mex67, which binds to the transcript and ferries it through NPCs. During cellular stress, such as heat shock, the export of housekeeping mRNA transcripts is halted, forcing these transcripts to remain inside the nucleus and ...

A Pathway To Solving The Structure Of Cl-Par-4 Tumor Suppressor Protein: Challenges & Findings, Krishna Raut, Samjhana Pandey, Andrea M. Clark, Komala Ponniah, Steven M. Pascal

College of Sciences Posters

Prostate apoptosis response-4 (Par-4) is a pro-apoptotic tumor suppressor protein. Down-regulation of this protein has been reported in a myriad of cancers. Conversely, up-regulation of Par-4 is found to be associated with several neurodegenerative disorders. Par-4 is unique in the sense it can selectively induce apoptosis in cancer cells. For this, caspase-dependent intracellular cleavage of Par-4 is essential to produce the functionally active fragment, cl-Par-4 (caspase-cleaved Par-4). The cl-Par-4 protein inhibits the NF-κB-mediated cell survival pathway and causes selective apoptosis in various tumor cells.

Our laboratory is interested in determining the structure of cl-Par-4 and understanding it’s interaction with ...

Investigation Of Oncogenic Ras And Endoplasmic Reticulum-Mitochondria Calcium Flux And Their Relationship In The Context Of Tumorigenesis, Emma Anderson

Senior Honors Theses

Intracellular calcium as a signaling molecule is a pervasive feature of cellular pathways, especially those that manage internal homeostasis and transitions through the cell cycle, so much so that regulated, responsive calcium flux between the endoplasmic reticulum (ER) and the mitochondria has been suggested to play a major role in cancer development. Another factor commonly implicated in tumorigenesis is RAS, an oncogene that controls signaling for many pathways that are also regulated by calcium. While both calcium and oncogenic RAS signaling are implicated in cancer development, possible links between them have yet to be determined. The identification of these links ...

Sars-Cov-2 Main Protease Inhibitors Repurposed For Hiv-1 Protease Binding, Jacob Minkkinen

CSBSJU Distinguished Thesis

Severe acute respiratory syndrome (SARS-CoV-2) led to the COVID-19 global pandemic, with over 460 million cases of infection and over 6 million deaths since the start of the pandemic. SARS-CoV-2 is a retrovirus that utilizes a main protease (Mpro). Mpro is a catalytic cys/his protease. Several treatments were proposed to stop the pandemic including repurposing drugs to inhibit the Mpro. Another retrovirus that uses a protease is human immunodeficiency virus (HIV-1) which has been a global epidemic for 40 years and is a devastating disease that attacks the immune system. HIV-1 has infected 79.5 million people and has ...