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Articles 1 - 30 of 37
Full-Text Articles in Life Sciences
Molecular Mechanisms Of Aberrant Protein Glycosylation In Pancreatic Cancer Stemness And Metastasis, Frank Leon
Molecular Mechanisms Of Aberrant Protein Glycosylation In Pancreatic Cancer Stemness And Metastasis, Frank Leon
Theses & Dissertations
A myriad of genetic and other abnormal changes underlies the aggressiveness and dissemination properties observed in pancreatic cancer (PC). Aberrant protein glycosylation is a commonly observed feature in PC. The modification of protein O-glycosylation is mediated by glycosyltransferases, which attach and sequentially elongate monosaccharides on Serine/Threonine (Ser/Thr) motifs. Aberrant glycosylation is recognized as an emerging hallmark of cancer where a disruption in normal glycosylation results in irregular O-glycans.
This dissertation research has investigated the consequences of aberrant protein glycosylation on stemness and enhancement of metastatic properties in pancreatic ductal adenocarcinoma (PDAC). Several publications have reported aberrant O-glycosylation increases in oncogenic …
Mechanistic Insights Into Diverse Protease Adaptor Functions, Nathan J. Kuhlmann
Mechanistic Insights Into Diverse Protease Adaptor Functions, Nathan J. Kuhlmann
Doctoral Dissertations
Protein degradation is an essential cellular process that helps maintain proper homeostasis. The ClpXP protease broadly regulates bacterial development and quality control during the cell cycle. The range and order of substrates that ClpXP degrades during the cell cycle is dictated by 3 accessory proteins, which are known as adaptors. This thesis will elaborate on how dimerization tightly regulates the stability and activity of the adaptor protein at the center of this hierarchy, RcdA, and show how this affects normal cellular processes in Caulobacter crescentus. I will discuss the mechanism by which dimerization limits RcdA activity and how the dimerization …
Analysis Of Single-Site Cysteine Mutation, I412c, In Human A Glycine Receptor States To Further Refine Structure And Allostery, Leah Engquist
Analysis Of Single-Site Cysteine Mutation, I412c, In Human A Glycine Receptor States To Further Refine Structure And Allostery, Leah Engquist
Honors Theses
The glycine receptor (GlyR) is the major inhibitory receptor in the brain and spinal cord. A member of the pentameric ligand gated ion channel superfamily, crystal structures are available but there are still unresolved areas, specifically the C-terminal tail and TM3-TM4 intracellular loop. Further refinement can provide deeper understanding of the molecular mechanism and allow the creation of novel therapeutics to modulate its function. We propose to insert a single cysteine mutation, I412C, into a Cys null background (C41S/C290A/C345S) to study non- conducting states (resting, desensitized) or with F207G/A288G mutations to study the open state. Purified, reconstituted GlyR is crosslinked …
High Altitude Ballooning As A Platform For Measuring Ozone Uptake Over Agricultural Landscapes, Thomas Sykora, Mark Potosnak
High Altitude Ballooning As A Platform For Measuring Ozone Uptake Over Agricultural Landscapes, Thomas Sykora, Mark Potosnak
DePaul Discoveries
Measuring plant health is a key aspect in maximizing crop outputs. One often overlooked risk to crop fields is damage caused by stomatal ozone uptake; measuring this uptake is an important tool in understanding crop losses. Traditional methods for measuring plant ozone uptake are prohibitively expensive and rely on equipment that cannot easily be moved. Here, we propose high-altitude weather ballooning as a cost-effective alternative for measuring ozone uptake on a regional (~10 km) spatial scale. Ozonesounde data was obtained with weather balloons launched from the National Oceanic and Atmospheric Administration research station in Boulder, Colorado. This data was then …
Mucinomics: A Bioinformatic Analysis Of Snail Mucins, And Their Function, Maxwell B. Mcdermott
Mucinomics: A Bioinformatic Analysis Of Snail Mucins, And Their Function, Maxwell B. Mcdermott
Theses and Dissertations
This thesis outlines the current research on secreted snail mucus, highlighting the potential of this biopolymer, and also demonstrates a research strategy to fulfill the unmet need of examining the hierarchical structures that lead to the enormous biological and chemical diversity of snail mucus genes.
Biochemical Evaluation Of Drug Inhibition Of Abc Transporters, Maisa Correa De Oliveira
Biochemical Evaluation Of Drug Inhibition Of Abc Transporters, Maisa Correa De Oliveira
Biological Sciences Theses and Dissertations
Multidrug resistant (MDR) cancers often become resistant to pharmacologically and structurally diverse drugs by overexpressing members of the family of ATP Binding Cassette (ABC) transporters. These membrane pumps protect normal cells by actively exporting a large range of toxins out of the cells. Classic MDR is often correlated with the overexpression of three well-studied mammalian ABC transporters: P-glycoprotein (P-gp), Breast Cancer Resistant Protein (BCRP), and Multidrug Resistant Protein 1 (MRP1).
P-gp is the most studied ABC transporter, and the search for P-gp inhibitors as co-therapeutics to combat MDR has had little success after decades of studies. We previously used high-throughput …
Application Of Artificial Intelligence And Machine Learning In Chemistry, Niraj Verma
Application Of Artificial Intelligence And Machine Learning In Chemistry, Niraj Verma
Chemistry Theses and Dissertations
In the last four years, I have been exposed to various topics in scientific research under the supervision of Dr. Kraka in the CATCO group. Numerous involved chemistry projects were undertaken to gain an understanding of the basic laws of nature involving vibrational spectroscopy, molecular acidity, and catalysts based on transition metals for halogen chemistry. The insights from computational chemistry were then applied to model and predict various complicated problems in chemistry via artificial intelligence. With the help of classical artificial intelligence, the non-covalent interactions governing the properties of proteins and water properties were analyzed. Significant improvements were made in …
Determination Of The Structure, Function, And Mechanism Of Type Iv Crispr-Cas Prokaryotic Defense Systems, Hannah Nicole Taylor
Determination Of The Structure, Function, And Mechanism Of Type Iv Crispr-Cas Prokaryotic Defense Systems, Hannah Nicole Taylor
All Graduate Theses and Dissertations, Spring 1920 to Summer 2023
Bacteria are under constant threat of invasion by bacteriophage (viruses which infect bacteria). To prevent bacteriophage from entering and overtaking the bacteria, bacteria utilize defense systems to identify and destroy foreign elements. One method of defense is called CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeats – CRISPR-Associated). Many different bacteria and most archaea use CRISPR-Cas systems. There are many diverse types of CRISPR-Cas systems, each of which provides defense in a slightly different way. One such CRISPR-Cas type is called type IV. The type IV CRISPR-Cas system is poorly understood and there are very few studies published on type IV …
Development Of High Value Oil Traits Using The Model Oilseed Crop Camelina Sativa, Evan Updike
Development Of High Value Oil Traits Using The Model Oilseed Crop Camelina Sativa, Evan Updike
Department of Biochemistry: Dissertations, Theses, and Student Research
Plant oils are an important source of food, fuel, and feed in our society today. The oil found in the seeds of plants is composed almost entirely of triacylglycerol (TAG) molecules, which consist of three fatty acids esterified to a glycerol backbone. As crude oil supplies decline, vegetable oils are gaining traction as a renewable substitute to petroleum-based materials in fuels, lubricants, and specialty oleochemicals. However, as it currently stands vegetable oils do not possess the properties necessary to fill the void of a petroleum free world.
To address this problem, plant biotechnologists have done extensive work on genetic engineering …
Ahr Expression On Rorc-Expressing Immune Cells Is Essential For I3c-Mediated Protection Against Colitis, Michal C. Williams
Ahr Expression On Rorc-Expressing Immune Cells Is Essential For I3c-Mediated Protection Against Colitis, Michal C. Williams
Senior Theses
Colitis is an inflammatory bowel disorder (IBD) whose etiology is attributed to modification in the luminal microbiota and dysregulation in the immune response. Indole is a signaling molecule which is naturally produced by gut luminal microbiota. Indole-3- carbinol (I3C) is a compound commonly found in vegetables and a ligand for the aryl hydrocarbon receptor (AhR). Previous studies have detected decreased expression and activation on the AhR receptor in colitis patients, thought to possibly alter gut microbiota metabolism, subsequently promoting colitis. 1 AhR, expressed in a variety of immune and epithelial cells, contributes to gut homeostasis by affecting vital mediators such …
High And Low Toxin Producing Strains Of Karenia Brevis Differ Significantly In The Redox Proteome, Lipid Profiles, And Xanthophyll Cycle Pigments, Ricardo Colon
FIU Electronic Theses and Dissertations
The dinoflagellate Karenia brevis, blooms annually in the Gulf of Mexico, producing a suite of neurotoxins known as the brevetoxins. The cellular toxin content of K. brevis, however, is highly variable between or even within strains. I investigated biochemical differences between high (KbHT) and low (KbLT) toxin producing cultures both derived from the Wilson strain, related to energy-dependent quenching (qE) by photosystem II, and the content of reduced thiols of the proteome. By characterizing the xanthophyll content of the two strains I was able to determine that KbLT performs qE inconsistently. To investigate the …
Investigating The Mechanism Of The Escherichia Coli Atp-Binding Cassette (Abc) Transporter Metni, Matthew Foronda
Investigating The Mechanism Of The Escherichia Coli Atp-Binding Cassette (Abc) Transporter Metni, Matthew Foronda
Master's Theses
Chemical homeostasis is a baseline requirement for any cell to survive. ATP-binding cassette (ABC) transporters play a vital role in homeostasis by importing nutrients and exporting toxins against their concentration gradients by utilizing the energy of ATP hydrolysis. Malfunctioning ABC transporters cause a variety of health problems, including cystic fibrosis, Stargardt’s disease (vision loss), and the development of drug-resistant tumors. An important step in solving these medical issues is to first understand the structure and mechanism of ABC transporters. Various studies have made great strides in depicting the structure and details of different ABC transporters and their mechanisms, however, many …
Dynamic Mechanisms Of Multidrug Resistance In Human Cancers And Gram Negative Pathogens, Lauren Ammerman
Dynamic Mechanisms Of Multidrug Resistance In Human Cancers And Gram Negative Pathogens, Lauren Ammerman
Biological Sciences Theses and Dissertations
This dissertation focuses upon dynamic agents of multidrug resistance (MDR). We used a combination of in silico and in vitro techniques to investigate two membrane transporters that confer MDR – P-glycoprotein, which confers MDR in human cancers, and MtrD, which confers MDR in Neisseria gonorrhoeae. Inhibitors targeting both proteins have tremendous potential for use as co-therapeutics in the treatment of multidrug resistant cancers, or of multidrug resistant infections. However, previously identified inhibitors of P-gp have failed clinical trials due to off-target effects and associated toxicities. Furthermore, the molecular mechanism of antibiotic transport by MtrD is poorly understood, and this dearth …
Mechanistic Studies Of Drug-Like Inhibitors Of P-Glycoprotein Using Atpase Assays, Electron Spin Resonance Spectroscopy And Cancer Cell Models, Gang Chen
Biological Sciences Theses and Dissertations
Multidrug resistance (MDR) in cancer and other diseases is frequently associated with transmembrane efflux proteins, one of which is P-glycoprotein (P-gp). Over-expression of P-gp in cancer cells increases the efflux of therapeutic drugs rendering them ineffective. In order to re-sensitize multidrug resistant cancers to chemotherapy, we have found potential inhibitors of P-gp by in silico screening methods, and several of these inhibitors were shown to successfully overcome MDR in the drug resistant DU145TXR prostate cancer cell line. The best of the identified hit compounds were further investigated with regard to the mechanism of inhibition using ATPase activity assays and electron …
Bringing Biochemistry Home: Transforming Milk Into Yogurt, Ashley King
Bringing Biochemistry Home: Transforming Milk Into Yogurt, Ashley King
Honors Theses
Communicating the beauty and complexity of biochemistry to students in a large classroom during the pandemic: what a challenge! We undertook a novel endeavor in the Department of Chemistry and Biochemistry by introducing a mandatory kitchen chemistry experiment in a lecture course. Milk, the epitome of our identity as mammals, also contains all of the major biochemical macromolecules studied in Biochemistry I. Further, the making of yogurt invokes physical processes that are the major processes and molecular forces that dominate the content of the course. Here, we report the results of massive parallel experiment conducted in the kitchens of the …
Chemical And Co-Solute Effects Of Polyethylene Glycol On I-Motif Formation, Lindsey Rutherford
Chemical And Co-Solute Effects Of Polyethylene Glycol On I-Motif Formation, Lindsey Rutherford
Honors Theses
DNA typically forms Watson and Crick double helix structures in which adenine, thymine, guanine, and cytosine pair with their complimentary DNA base. However, DNA i-motif structures can form in cytosine rich DNA, typically under slightly acidic conditions (~pH 6). DNA i-motifs are four stranded secondary structures in which cytosine pairs with cytosine to form a quadruplex. The i-motifs are typically formed in acidic conditions because of the protonation in the C•C base pair between one of the three hydrogen bases. Recent studies have suggested i-motifs can also form under neutral conditions, which is more realistic for a cell. It is …
Effects Of Crowding Agents On I-Motif Dna, Hayden Brines
Effects Of Crowding Agents On I-Motif Dna, Hayden Brines
Honors Theses
Deoxyribonucleic acid (DNA) is a well-known double stranded, helical, biological molecule. In addition to its more commonly known structure, DNA can also form more complicated structures like G-quadruplexes and i-motifs (iM). The iMs are formed by cytosine rich DNA and are a four stranded structure that is typically looped around itself. The iM formation is typically pH-dependent and is favored in more acidic conditions; the pKa value is approximately 6.5. This pKa value allows for potential in vivo formation, since the cells have a pH of approximately 7.3. Due to this, iMs are thought to be powerful, innovative molecules for …
Pectin And Alginate Extraction To Treat Liquid Cafo Manure, Clare Sunderman
Pectin And Alginate Extraction To Treat Liquid Cafo Manure, Clare Sunderman
Honors Projects
For this project, various extraction methods were used to extract pectin from Pastinaca Sativa and alginate from Macrocystis. These extractions were then dried and used in treating 250mL of manure along with a CaCl2 or FeCl3 coagulant. It was found that CaCl2 was not as effective as FeCl3 in coagulating manure. But the results obtained suggest that pectin and alginate obtained with a simpler extraction method is just as effective as the highly purified and refined pectin and alginate produced for the food industry, in the treatment of CAFO manure. The liquid portion of the …
Detection And Quantification Of Γ-H2ax Using A Dissociation Enhanced Lanthanide Fluorescence Immunoassay, Felicite K. Noubissi, Amber A. Mcbride, Hannah G. Leppert, Larry J. Millet, Xiaofei Wang, Sandra M. Davern
Detection And Quantification Of Γ-H2ax Using A Dissociation Enhanced Lanthanide Fluorescence Immunoassay, Felicite K. Noubissi, Amber A. Mcbride, Hannah G. Leppert, Larry J. Millet, Xiaofei Wang, Sandra M. Davern
Biology Faculty Research
Phosphorylation of the histone protein H2AX to form γ-H2AX foci directly represents DNA double-strand break formation. Traditional γ-H2AX detection involves counting individual foci within individual nuclei. The novelty of this work is the application of a time-resolved fluorescence assay using dissociation-enhanced lanthanide fluorescence immunoassay for quantitative measurements of γ-H2AX. For comparison, standard fluorescence detection was employed and analyzed either by bulk fluorescent measurements or by direct foci counting using BioTek Spot Count algorithm and Gen 5 software. Etoposide induced DNA damage in A549 carcinoma cells was compared across all test platforms. Time resolved fluorescence detection of europium as a chelated …
Mediation Of The Uncoupled Enos Pathway Following Oxidative Stress Using Tetrahydrobiopterin And Nitric Oxide Donor Drugs To Restore Tetrahydrobiopterin Concentration, Brianna Munnich
Scholar Week 2016 - present
Presentation Location: Warming House, Olivet Nazarene University
Abstract
The eNOS pathway, found in the endothelium of blood vessels, is a key regulator of nitric oxide levels in the circulatory system. The pathway is controlled through several positive and negative feedback loops [2]. The cofactor tetrahydrobiopterin (BH4) is a major control point in this pathway and under conditions of stress can be reduced into the dihydrobiopterin (BH2) [2,6,7,8,9]. When the reduced form is predominant, the pathway produces reactive oxygen species (ROS) rather than nitric oxide, causing stress and damage to the vessels [6,7,8,9]. In this study, different treatments were studied …
Protein Composition: Translating Amino Acid Sequences Into Music, Melody Campbell
Protein Composition: Translating Amino Acid Sequences Into Music, Melody Campbell
WWU Honors College Senior Projects
Proteins are composed of individual building blocks (amino acids) assembled in a chain, resembling beads on a string. This string – or sequence of amino acids – folds into a unique three-dimensional shape to form a fully functional protein. In nature, there are 20 different naturally occurring amino acids. I assigned specific musical chords to each different amino acid and arranged the chords sequentially in an order that mirrored the sequence of amino acids. The resulting composition contains a pattern of chords representative of the protein’s amino acid sequence. For example, if Glycine (one of the 20 natural amino acids) …
Structural Analysis Of Protein-Peptide Interactions, Melody Gao
Structural Analysis Of Protein-Peptide Interactions, Melody Gao
WWU Honors College Senior Projects
Over the last three years in the Amacher lab, I have been fortunate to work on two amazing projects studying protein-peptide interactions: PDZ domains and Class A sortases. Both recognize a certain substrate motif, and we are interested in these proteins' selectivity and promiscuity of their substrate.
Purification And Functional Characterization Of The Iron-Responsive Transcription Factor Aft1 From C. Glabrata, Jade Ikahihifo-Bender
Purification And Functional Characterization Of The Iron-Responsive Transcription Factor Aft1 From C. Glabrata, Jade Ikahihifo-Bender
Senior Theses
Due to its unique ability to serve as both an electron donor and acceptor, iron is utilized as a co-factor for many biological processes, including electron transfer, oxygen binding, and vitamin synthesis. Iron is also a key factor during fungal infections as the human host and invading pathogens battle over limited iron pools. The primary iron-responsive transcription factor Aft1 in the opportunistic pathogenic yeast Candida glabrata responds to iron deficiency by activating expression of iron acquisition genes. However, the mechanisms for sensing intracellular iron levels and regulating Aft1 activity in response to iron are unknown. The C. glabrata iron regulation …
Lions, Tigers, And Hemes - Oh My! A Dynamic Look At The Electronic Effects Of Porphyrin Substitution On Cytochrome P450 Olet, Alexis J. Holwerda
Lions, Tigers, And Hemes - Oh My! A Dynamic Look At The Electronic Effects Of Porphyrin Substitution On Cytochrome P450 Olet, Alexis J. Holwerda
Senior Theses
OleT, a member of the CYP152 family of cytochrome P450s (CYPs), decarboxylates fatty acids using hydrogen peroxide as an oxidant. The resultant products are a terminal alkene and carbon dioxide. This C–C cleavage reaction is highly atypical for CYPs, which prototypically oxygenate substrates, and provides a potential means to enzymatically produce drop-in fuels. OleT contains a heme-iron cofactor that facilitates decarboxylation through the activation of hydrogen peroxide. The catalytic cycle, as determined by transient kinetics, includes two ferryl intermediates known as Compound I (Ole-I) and Compound II (Ole-II). Ole-I performs substrate hydrogen abstraction and subsequent single electron transfer to Ole-II …
Osmosis - Spring 2019
Osmosis Magazine
Osmosis is a student read, led, and written publication from the University of Richmond, focusing on all aspects of healthcare and science.
Osmosis - Fall 2019
Osmosis Magazine
Osmosis is a student read, led, and written publication from the University of Richmond, focusing on all aspects of healthcare and science.
Engineering Src Homology 2 Domains With Improved Specificity For Sulfotyrosine, Anya Morozov
Engineering Src Homology 2 Domains With Improved Specificity For Sulfotyrosine, Anya Morozov
Honors Theses
Protein tyrosine O-sulfation (PTS) is a common post-translational modification that has been implicated in a variety of biological processes and human illnesses. Despite continued progress in the field of sulfoproteomics, the extent and function of sulfated tyrosine (sulfotyrosine) residues is a topic of ongoing research. Previous work in the Guo Lab has identified Src Homology-2 (SH2) mutants that have a high affinity for sulfotyrosine along with retained high affinity for their natural ligand, phosphorylated tyrosine (phosphotyrosine). In this thesis, I attempted to generate SH2 mutants that have high affinity and specificity for sulfotyrosine over phosphotyrosine. While I successfully generated …
Microsatellites And Their Association With Break Induced Replication, French J. Damewood Iv
Microsatellites And Their Association With Break Induced Replication, French J. Damewood Iv
Browse all Theses and Dissertations
To study microsatellites instability and their repair pathways a dual fluorescent (DF2) and selectable (ganciclovir sensitive/ thymidine kinase (TK) expressing) cell system was assayed using replication fork stalling agents hydroxyurea and telomestatin. These cell lines carried ectopically integrated microsatellites derived from the Dystrophia Myotonica Protein Kinase (DMPK) gene ((CTG)102 microsatellite), or an 88 bp polypurine/ polypyrimidine (Pu/Py) repeat from the PKD-1 locus, inserted into a FLP recombinase target site. These microsatellites form non-B DNA structures in -vivo and in-vitro causing replication fork stalling and double strand breaks. DF2 myc (CTG)102 -TK cells treated with hydroxyurea were assayed for mutagenesis of …
Enzymatic Post-Translational Halogenation For Adding Functionality To Biomaterials, Alexander L. Compean
Enzymatic Post-Translational Halogenation For Adding Functionality To Biomaterials, Alexander L. Compean
Browse all Theses and Dissertations
Silk fibroin from the silkworm, Bombyx mori, is a unique biomaterial that has been extensively studied for a variety of applications due to its promising properties such as controllable self-assembly, robust mechanical properties, and biological compatibility. Previously, there have been numerous methods describing the chemical modification of silk fibroin that utilize synthetic or enzymatic means that do not use halogens as a means of functionalization. Herein, a halogenation strategy is presented to modify silk fibroin with the aim of developing a novel functional material through the carbon-halogen (C-X) bond. Modification with NaX (X = Cl, Br, and I) salts, hydrogen …
The Implications Of Case-Based Learning (Cbl) On Biochemistry Education: An Integrative Literature Review, Ryan C. Ripert
The Implications Of Case-Based Learning (Cbl) On Biochemistry Education: An Integrative Literature Review, Ryan C. Ripert
Honors Undergraduate Theses
The COVID-19 has significantly impacted the world as we know it, especially in higher education institutions. In response to COVID-19, most colleges and universities were forced to close their doors to students and switch to online learning over Zoom. Although most students are adjusted well to this new mode of education, other students, such as individuals pursuing degrees in the sciences, have difficulty adapting to the online mode of instruction. Case-based learning (CBL) is considered one of the best strategies in teaching a course like Biochemistry in a large classroom setting. Implementing CBL in biochemistry education may increase student engagement …