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Chemistry

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  • ItemEmbargo
    Identification and Quantitation of Cannabinoid Solute-Column Interactions Using the Hydrophobic-Subtraction Model to Predict Separation in High-Performance Liquid Chromatography
    (East Carolina University, July 2024) Tunnell, Heather Kaye
    The Hydrophobic-Subtraction Model (HSM) has been widely used for identification of similar and orthogonal chromatography columns since its inception in 2002 but only had limited uses as a predictive tool. Recent refinement of the model has improved the prediction accuracy to a level that offers promise for use in high-performance liquid chromatography (HPLC) separation development. The HSM quantitatively describes the parameters affecting solute retention on HPLC columns including hydrophobic, steric, hydrogen-bond, cation exchange, and dipole interactions. To demonstrate the process, 16 cannabinoid compounds were chosen as the test solutes due to increasing interest and applications. The HSM was used to identify and quantify the various cannabinoid solute retention parameters based on actual retention of each solute on a set of calibration columns with previously quantified column retention parameters. The resulting solute parameters were used to predict relative retention of each cannabinoid on over 550 columns in the HSM column database. A sorting system was then developed to rank the columns. Overall, this Thesis demonstrates the application of the HSM to cannabinoid compounds starting with identification of the best columns for the separation of these solutes.
  • ItemEmbargo
    Elucidation of The Roles of Metal Ions in Misfolding and Aggregation of TTRwt and TTR-V30M Associated with ATTR Amyloidosis
    (East Carolina University, July 2024) Burton, Kelley
    Misfolding and aggregation of transthyretin causes a range of diseases, many of which are caused by mutations and destabilization of the protein. Known diseases related to the protein include cardiomyopathy, polyneuropathy, and transthyretin amyloidosis, along with other ailments 1,2,3. The mechanism by which these diseases and many others occur is currently unknown. Through previous studies, metals have been shown to induce aggregation of these proteins in which case it is hypothesized to have an impact on the mechanism’s pathway 4,5. Specifically, Zn2+ ions at significantly higher levels have been observed to induce ex-vivo TTR aggregates in patients affected by amyloidosis compared to those with no current signs of the disease5. The effectiveness of Ca2+ ions in triggering the neurodegenerative process linked to polyneuropathy is crucial in understanding the role of the metal 5. Each of these metals has shown potential possibilities of their specific roles in interactions with transthyretin. Through this study, Zn2+ and Ca2+ ions were used throughout different experiments. WT TTR is a known native form of transthyretin that becomes unstable over time in the structural form1. This protein will be used in comparison with TTR-V30M as it is one of the most common mutations with an association with familial amyloid polyneuropathy (FAP)3. In this thesis, biophysical techniques such as aggregated kinetics, circular dichroism, and isothermal titration calorimetry were used to examine the effects of the metal ion binding. The aim of this study is to investigate the effects of the metal ions on the structure and dynamics of the protein associated with misfolding and aggregation. The biophysical analyses revealed the metal ion bindings induced local structural/ dynamical changes of the protein, promoting misfolding and aggregation.
  • ItemEmbargo
    Elucidation of the Roles of Metal Ions in Misfolding and Aggregation of Pathogenic TTR Variants Associated with ATTR Amyloidosis
    (East Carolina University, July 2024) Irving, Robert
    Transthyretin (TTR) is a homo-tetrameric transport protein that is responsible for carrying the thyroid hormone, thyroxine (T4) and retinol (vitamin A1) via retinol binding protein in both human plasma and cerebrospinal fluid. The native TTR tetramer is highly stable but can be destabilized under certain conditions such as single-point mutations, acidic pH, and elevated metal concentrations. Destabilization of the tetramer results in its dissociation into monomers leading to misfolding, aggregation, and amyloid fibril deposition in various soft tissue organs eventually causing a set of diseases with cardiomyopathic and neuropathic manifestations known as Transthyretin Amyloidosis (ATTR). The deposition of wild type derived amyloid fibrils leads to a non-hereditary form of ATTR known as ATTRwt. With symptoms manifesting as both polyneuropathic and cardiomyopathic, this condition affects approximately 25% of the male population above the age of 80 and is the primary cause of death for supercentenarians. However, it is the hereditary transthyretin amyloidosis (ATTRv), caused by significantly increased rates of aggregation due to single point mutations, that are of particular concern. There are over 120 amyloidogenic variants of TTR that significantly increase the pathogenicity of TTR aggregation. These variants are primarily cardiomyopathy and polyneuropathy causing, though many variants lead to amyloidosis with mixed phenotype. In addition to this, many patients with either cardiomyopathy or polyneuropathy report ocular, GIT, and renopathic manifestations along with their primary phenotype. The most aggressive TTR variants cause significant damage to the central nervous system, leading to progressive dementia, ataxia, and stroke-like symptoms. Two TTR variants will be investigated in this study. The variant L55P, which replaces the lysine at position 55 with a proline, is the most pathogenic TTR mutation and often manifests with mixed phenotypes leading to varying combinations of cardiomyopathic and polyneuropathic symptoms. The variant V122I, replacing the valine at position 122 with an isoleucine is the most common mutation in the United States, carried by approximately 4% of African Americans and is primarily cardiomyopathy causing. With the presence of zinc found in ocular TTR amyloid extracts and microcalcification in cardiac extracts, it has been theorized that these physiological metals may play a more key role in ATTR pathogenesis, like those in Alzheimer’s related proteins. As such, experiments were developed to observe the effect zinc and calcium on TTR aggregation under physiological pH. Understanding the roles these metals play in vitro can offer insight into what might be occurring in vivo. Additionally, since there are currently only therapies associated with stabilizing the native TTR tetramer, determining other factors in TTR amyloid formation can create opportunities for multiple approaches to treatment.
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    Electrochemical Detection of Polyphosphate Accumulation by Phosphate Accumulating Organisms for Wastewater Treatment
    (East Carolina University, July 2024) Cobb, Davis D
    Inorganic phosphates are a very common additive to fertilizers used in industrial agriculture. While these additions result in larger healthier crop yields the runoff from these macronutrients ends up within local water ecosystems. The discharge of phosphate to water systems can lead to eutrophication and long-term damage to the local environment. To treat phosphate, local wastewater treatment systems (WWTP) often use bacteria to remove phosphate from the water. These phosphate treatment organisms are termed phosphate accumulating organisms (PAO) and sequester phosphate by converting it into long chains of polyphosphate. The efficiency of this process can vary due to myriad factors; therefore, the ability to monitor if the biological processes are occurring normally is a significant WWTP need. To this end, an electrochemical biosensor was developed using Layer-by-Layer (LbL) methodology to immobilize films containing Pseudomonas putida, a model PAO, to detect polyphosphate uptake following soluble phosphate exposure. The bacterial films were exposed to electroactive methylene blue and phosphate with electrochemical monitoring using square wave voltammetry to determine methylene blue reduction currents. Currents at several potentials (vs. SCE) increase as a function of phosphate exposure, which were significantly elevated in the presence of P. putida vs. E. coli films. ICP-MS was used to show that P. putida sequesters phosphorus in significantly higher amounts than E. coli, which shows that the electrochemical output is due to poly-P accumulation on the electrode surface. The sensor was challenged with interfering ion solutions and at varying temperatures to model conditions that might be encountered at the WWTP. Overall, this study lays the groundwork for the eventual biosensor use to measure PAO health and function at WWTP.
  • ItemEmbargo
    Biochemical Characterization of a New Subfamily of Unusual Pathogenic Fungal Lipoxygenases
    (East Carolina University, July 2024) Hill, Gage
    Lipoxygenases (LOX) are a family of enzymes that catalyze the (per)oxidation of polyunsaturated fatty acids. Over the last 30 years, fungal lipoxygenases have drawn interest because of their potential role in plant pathogenesis. This family of LOXs is distinct from the canonical LOXs in plants and animals due to i) nature of their metal center, ii) formation of a unique bis-allylic product, iii) post-translation, N-linked glycosylation, and iv) secreted from their host organism and implicated in pathogenesis. To date, six fungal LOXs have been biochemically characterized. A recent bioinformatics study revealed a potential new subfamily of fungal lipoxygenases, which deviate from the six ‘prototype’ fungal LOXs. These so-called ‘class II’ fungal LOXs have a cysteine amino acid where an otherwise conserved leucine residue is found across all LOXs. The Leu is considered a “substrate clamp” and previous mutations of this residue to volume-reducing alanine are linked to impairment of enzyme activity. Currently, there is no biochemical data reported for these putative class II fungal LOX enzymes. Herein, we use a combination of biochemical characterization methods and protein modeling to analyze three representative class II LOXs. The enzymes were successfully isolated from yeast expression cultures but showed no enzyme activity. AI generated structural models coupled with circular dichroism spectroscopy suggest that these enzymes fold similarly to that of LOXs, including nearly identical primary coordination sphere residues. Metal analysis indicates that the proteins can accommodate manganese or iron, consistent with other LOXs. To understand the functional consequence of these non-conserved mutations, a Leu-to-Cys variant was prepared for a paradigm plant LOX from soybean seeds. This variant is catalytically impaired. The collective data indicates that the class II LOXs are not effective at LOX activity; their potential biochemical function is discussed.
  • ItemOpen Access
    Theoretical Studies of S100 Proteins using the Accelerated Molecular Dynamics and Nudged Elastic Band Methods
    (East Carolina University, July 2024) Gates, Austin Nathaniel
    The use of calcium as a secondary messenger is an important aspect of many biological pathways. Through binding calcium ions, some proteins can undergo conformation changes required for biological activity. Understanding the mechanisms by which calcium binding and conformation changes occur, we can better treat pathologies associated with these proteins. The S100 protein family is highly conserved and is implicated in a number of biological systems due to their interactions with effector proteins. These interactions are dependent on both calcium and target protein concentrations, inducing the formation of a hydrophobic patch region. In this work, accelerated molecular dynamics and nudged elastic band methods were applied to investigate the calcium induced conformation pathways of the S100A6 protein. Accelerated molecular dynamics was used in the isolation of structures suitable to act as starting and end points in nudged elastic band pathways and in mutation studies. Multiple nudged elastic band simulations were completed to obtain adequate sampling of the S100A6 conformation pathway. Pairwise distance calculations revealed distinct calcium binding site formation, occurring in a stepwise fashion. The calculation of distance and angle of the hydrophobic patch constituents revealed the presence of a long-lived intermediate conformation. MMGBSA calculations allowed for the identification of K31, D50, and E67 as important residue contributors to patch formation. Residues K31 and D50 were identified as key mechanisms responsible for secondary structure rearrangement and stabilization. Residue E67 was identified as a potential communication mechanism between calcium binding loops, potentially assisting in cooperative binding. Mutation to these residues strongly supported the identified roles of these residues. The application of SASA calculations in these mutated systems revealed significant changes due to the absence of these residues in both apo and holo conformations. Further, accelerated molecular dynamics and nudged elastic band methods were also applied to the S100B system. Structural start and end points used in nudged elastic band simulations were identified through accelerated molecular dynamics simulations. The goal of this study was to identify mechanisms comparable to those discovered in S100A6. Pairwise distance calculations revealed similar yet unique pathways of calcium binding site formation due to structural differences. The presence of a long-lived intermediate conformation was also identified in S100B through distance and angle calculations of secondary structure elements. MMGBSA calculations revealed mechanisms similar to those in S100A6 that include comparable residues. Residue K30 in S100B was identified to have remarkably similar behavior to K31 in S100A6, having key roles in both sensing initial calcium binding and formation of the hydrophobic patch region. Residue E52 and D55 in S100B were identified to have similar function to D50 in S100A6, functioning to stabilize the hydrophobic patch in conjunction with K30. Initial review of other S100 protein systems identified residues that appear comparable to both K31 and K30 in S100A6 and S100B, respectively. Further study of the S100 protein family is vital to understanding the role of these proteins in various pathologies and we believe many of the mechanisms identified in this work are present in other S100 proteins.
  • ItemEmbargo
    Complementary Square Wave Voltammetry and LC-MS/MS Analysis to Elucidate Induced Damaged and Mutated Mitochondrial and Nuclear DNA from Biological Organisms
    (East Carolina University, July 2024) Lafave, Elizabeth Rose
    Electrochemical methods coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) were developed and applied to rapidly analyze DNA structure, sequence variations, and damage in biological systems. Square wave voltammetry (SWV) at pyrolytic graphite electrodes with immobilized DNA allowed detection of guanine oxidation peaks catalyzed by Ru(bpy)32+. Peak current differences compared to wild-type (WT) or unaltered samples indicated DNA structural changes, which were validated through LC-MS/MS base compositional analysis of hydrolyzed DNA samples. Breast cancer 1, early onset (BRCA1) gene codes for the DNA repair enzyme Brca1 and impacts skeletal muscle function when mutated. To study Brca1's role, inducible skeletal muscle-specific BRCA1 knockout (KO) mice were generated. Initial phenotypic assays indicated increased mitochondrial DNA (mtDNA) mutation frequency in KO vs wildtype (WT). Applying the electrochemical approach, mtDNA from Brca1 KO skeletal muscle displayed statistically significantly decreased oxidative currents vs. WT, consistent with guanine depletion due to mtDNA mutations. Conversely, nuclear DNA (nDNA) showed increased currents in KO samples, suggesting accumulation of oxidatively damaged guanine (p < 0.05). Subsequent LC-MS/MS composition analysis validated these hypotheses, allowing us to quantify suspected guanine variations, as well as detect the remaining DNA bases (adenine, thymine and cytosine) and commonly damaged bases (8-oxoguanine, fapyadenine). The electrochemical – LC-MS/MS approach was further utilized to study the role of overexpressed Brca1 in various muscle locations, detect and identify DNA variations in Ni2+- treated Caenorhabditis elegans, study genetic changes in additional mouse models (i.e. Col5a1 for Ehlers-Danlos, MDX for muscular-dystrophy), and monitor DNA change in Hydrogenophaga taeniospiralis, a benzene-exposed bacteria. Combining electrochemical and mass spectrometry techniques allowed for validation of DNA structural changes observed in phenotypic studies, while also providing a versatile approach to comprehensively investigate a wide range of biological questions, as well as chemical analyses of historical artifacts. Finally, further utilization of analytical methodology, predominantly LC-MS/MS, for historical medicines provided insight into often unlisted ingredients and potential contaminants, addressing lingering historical biases towards alternative treatments during the 19th century.
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    Computational Investigation of the Annexin A2-Membrane Interaction and Annexin A2-Induced Microdomain Formation
    (East Carolina University, July 2024) Lindsay, Sam Joseph
    Computational methods including molecular dynamics and molecular docking were utilized to investigate multiple facets of the peripheral membrane binding protein, Annexin A2 (A2). The combined works are presented here as five independent studies. All atomic molecular dynamics simulations were used to conduct the first two studies on the heterotetrameric A2/p11 complex. The first investigated the impact of Ca2+ on the organization of membrane and F-Actin binding sites found within the heterotetramer. It was shown that Ca2+ modulates the availability of key membrane-binding residues and the stability of F-Actin-binding C-terminal residues of A2. The second study investigated the organization of the heterotetramer on the surface of a membrane model. A model of the heterotetramer consistent with measurements from the literature was generated. Additionally, previously unreported interactions between p11 and the membrane were observed. A2 has been implicated in a variety of pathologies where its inhibition would be desirable. A study was undertaken to identify potential inhibitors of A2-membrane binding activity. The stability of A2-ligand binding and effects of ligand binding on A2-membrane interactions was assessed via molecular dynamics simulation. Multiple ligands were identified that disrupt A2-Ca2+ binding and A2-membrane binding. The final two studies involved modelling A2-induced PIP2 microdomain formation. A novel Python package, called MMAEVe, was developed that facilitates the creation of biological-scale membrane-protein models. For the final study, MMAEVe was used to generate a system of A2 surrounding a vesicle. Coarse-grained molecular dynamics simulations were run for the system and the process of A2-induced PIP2 microdomain formation was observed. It was shown that the process occurs in three steps, A2-membrane association, localized PIP2 clustering, and A2 aggregation causing local PIP2 clusters to merge into microdomains. A novel method was developed to track microdomain formation which utilizes the Fréchet mean to define a system-appropriate variance measurement.
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    A Catalytic Approach to Cyclopentenones: Unexpected Challenges in Synthesizing Pent-2,4-dienals
    (East Carolina University, 2023-05-04) English, Hunter Wade
    Transition metal catalysis has long been utilized to facilitate a number of chemical reactions outside the scope of traditional organic chemistry. Because of this, there has been a growing interest in the community in utilizing C-H bonds over C-X bonds as synthetic alternatives with better thermodynamic conditions (lower temperatures, pressures, energies, etc.) and forming C-C bonds. For example, rhodium-catalyzed hydroacylation can be used in the conversion of 4-pentenals to cyclopentanones. The mechanistic foundation of this reaction was applied to the synthesis of chiral 3-substituted indanones, unlocking a whole series of transformations towards the construction of biologically active molecules. The Morehead group recently proposed an alternate synthesis of cyclopentenones via a rhodium-catalyzed intramolecular hydroacylation reaction of penta-2,4-dienals by the following reaction sequence: 1. Vilsmeier-Haack Formylation to form 3-bromo-2-enals, 2. Suzuki Cross-Coupling with vinylboronates, and 3. Hydroacylation. Indeed, all reaction steps were performed successfully starting from acetophenone and allylboronic acid pinacol ester, resulting in 4-methyl-3-phenyl-2-cyclopenten-1-one. However, some surprising results were obtained along the way. It was found that when 3-bromo-3-phenyl-2-propenal underwent Suzuki Cross-Coupling, an unexpected mixture of pent-2,4-dienal isomers was obtained. To investigate this matter, a number of reaction conditions were examined in hopes of finding one with optimal yields and little to no isomerized pent-2,4-dienal product. In addition, a variety of cyclopentenones were synthesized to explore the steric effect in influencing the isomerization process. Some potential mechanistic details of this strange isomerization phenomenon along with results obtained from the synthesis will be reported and discussed.
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    Towards Establishing Methods of Synthesis, Purification, and Structural Determination for Human Fibrinogen
    (East Carolina University, 2023-05-04) Kirby, Nicholas Carter
    Fibrinogen is a prevalent blood-based glycoprotein. In its polymerizable form, fibrin, it serves as the structural component of blood clots and helps to incorporate red blood cells, macrophages, and fibroblasts to the wound-site. Fibrinogen plays important roles in inflammation and tissue regeneration, regulating growth factor receptor pathway activation, scar formation, and immune response, yet many questions remain about fibrinogen's structure-function link in these various pathophysiological states. Studies focused on improving expression systems for recombinant fibrinogen, and developing more rapid and robust techniques for purifying fibrinogen from complex media would provide a means by which to progress mutational studies of fibrinogen. Similarly, developing methods for high-resolution imaging of fibrinogen in its native, aqueous-based environment is necessary to establish proper structure-function relationships encompassing this complex 340 kDa glycoprotein. The work described in this thesis produced advancements in each of these crucial areas of fibrinogen research. Herein, chapter 2 reports, to our knowledge, the first methodology of transient recombinant human fibrinogen expression using suspension HEK Expi293TM cells. A highly selective and robust affinity-based approach was also developed for the rapid isolation of fibrinogen from a variety of complex media. Chapter 3 describes cryogenic electron microscopy and our process of obtaining a high-resolution, in-solution structure of human fibrinogen's D region. This structure is currently the highest resolution structure of any fibrinogen domain obtained in the native, solution state and further supports evidence for fibrinogen's intrinsic flexibility, expanding the textbook representations of fibrinogen as a rigid, rod-like structure. Lastly, future directions outlining fibrinogen's role during pregnancy and unique fibrinogen-specific protofibril-like structures are discussed. In an appendix, I have included figures from an illustrated review journal article, which I participated in as a co-first author.
  • ItemOpen Access
    Improving Prostamide Anti-Cancer Activity Through Derivatization and Micellar Delivery
    (East Carolina University, 2023-04-28) Halatek, David
    Colorectal cancer is the fourth most common cancer diagnosis per year as well as the fourth highest rate of death per year according to the Centers for Disease Control. Approximately 1/3rd of the diagnosed colorectal cancer cases per year will result in death. Prior research from our group has shown that the prostaglandin-ethanolamide 15-deoxy, [delta]12,14 prostamide J2 (15d-[delta]12,14-PMJ₂) is selectively toxic to murine melanoma cells (B16F10) and murine colorectal cells (CT-26) both in vitro and in vivo and significantly reduces tumor growth. Further, 15d-[delta]12,14-PMJ₂ induces cell death in primary patient melanoma cells and thus may be a promising therapeutic. As 15d-[delta]12,14-PMJ₂ can be made by the condensation of ethanolamine with 15-deoxy, [delta]12,14 prostaglandin J₂ (15d-[delta]12,14-PGJ₂), we sought to test the cytotoxicity of other prostamide derivatives to determine the structural features required for activity. Based on prior results in a study of related prodrugs, 15d-[delta]12,14-PMJ₂-Arvanil was selected as the top candidate for testing anti-cancer activity. After testing in both a human and murine cell line, it was determined that 15d-[delta]12,14-PMJ₂-Arvanil was not as cytotoxic as 15d-[delta]12,14-PMJ₂. It is possible that the bulkier functional group on the [alpha]-chain of the prostamide prevents transport into the cell the same way or to the same degree 15d-[delta]12,14-PMJ₂ enters. In an effort to test this hypothesis, and to develop an improved means for systemic delivery for this class of hydrophobic prostamides, engineered micelles composed of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] and D-[alpha]-tocopherol polyethylene glycol 1000 succinate were investigated as drug carriers.
  • ItemOpen Access
    Complementary Square Wave Voltammetry and Tandem Mass Spectrometry Analysis to Identify and Detect Compensatory Genomic Changes in Nematodes Due to Nickel (II) Exposure
    (2022) LaFave, Elizabeth R.; Turner, Ryne; Schaaf, Nicholas J.; Hindi, Thekra; Rudel, David; Hvastkovs, Eli G.
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    Red Blood Cell Preservation Under Austere Conditions
    (East Carolina University, 2023-01-05) Angermeier, Tori Marena
    In the United States, the maximum approved preservation time for red blood cells under hypothermic storage conditions is 42 days when treated with an appropriate additive solution, namely AS-1. In this investigation, we analyze the possible protective properties of sucralose alone, in combination with, and as an added ingredient to the AS-1 preservation solution. Absorbance measurements were used to monitor the amount of free hemoglobin found in the supernatant for the variety of different treatments investigated. Blood treated with sucralose alone did not show to minimize hemolytic leakage as well as the current standard, whereas red cells treated with the modified AS-1 solution where sucralose replaced the mannitol constituent showed similar results to that of the current standard. Statistical analysis revealed that no significant difference between the standard AS-1 solution and the modified AS-1 solution was observed when all studies were integrated together. Osmotic fragility experiments were conducted to assess if the membrane flexibility was compromised due to the addition of sugar during incubation by quantifying the percent hemolysis at various salt concentrations. Analyses determining the concentration of salt required to induce 50% hemolysis, known as the IC50 value, were used to compare the treatments. Red cells treated with sucralose alone showed higher IC50 values, which is associated with red cell membrane rigidity. Lower IC50 values were observed for blood treated with the modified AS-1 solution, which showed no statistical significance in comparison to that of the standard AS-1 solution when all studies were considered. Potassium assays were conducted to measure potassium leakage as a function of time in storage. Blood samples treated with sucralose alone reached equilibrium more quickly, suggesting sucralose alone does not retard the leakage of potassium as well as the current standard. Red cells treated with the modified AS-1 solution showed similar results to the current standard as the rate of potassium leakage was the same. Cellular morphology studies were conducted to observe the morphological changes red blood cells undergo during extended preservation periods. Blood treated with sucralose alone reach undesirable morphologies more quickly when compared to the current standard, suggesting sucralose alone does not preserve the membrane as well as the standard. Red cells treated with the modified AS-1 storage solution showed to retard the progress to undesirable morphologies better than that of the standard AS-1 solution as the cells maintained discocyte and echinocyte structures for longer periods of time with no red cell fragmentation throughout the duration of time in storage.
  • ItemOpen Access
    CRY–BARs: Versatile Light-Gated Molecular Tools for the Remodeling of Membrane Architectures
    (2022-08-18) Wurz, Anna I.; Hughes, Robert M.; Bunner, Wyatt P.; Szatmari, Erzsebet M.
  • ItemOpen Access
    Development of Transient Recombinant Expression and Affinity Chromatography Systems for Human Fibrinogen
    (2022-01-19) Popovic, Grega; Kirby, Nicholas C.; Daub, Caroline E.; Offenbacher, Adam R.; Dement, Taylor C.; Belcher, Heather A.; Hudson, Nathan E.
  • ItemOpen Access
    Collective ERK/Akt Activity Waves Orchestrate Epithelial Homeostasis by Driving Apoptosis-Induced Survival
    (2021-06-21) Hughes, Robert M.; Gagliardi, Paolo Armando; Dobrzyński, Maciej; Jacques, Marc-Antoine; Dessauges, Coralie; Ender, Pascal; Blum, Yannick; Cohen, Andrew R.; Pertz, Olivier
  • ItemOpen Access
    Kinetic and Structural Investigations of Novel Inhibitors of Human Epithelial 15-Lipoxygenase-2
    (2021) Ohler, Amanda; Offenbacher, Adam R.; Tsai, Wan-Chen; Gilbert, Nathaniel C.; Armstrong, Michelle; Perry, Steven; Kalyanaraman, Chakrapani; Yasgar, Adam; Rai, Ganesha; Simeonov, Anton; Jadhav, Ajit; Standley, Melissa; Lee, Hsiau-Wei; Crew, Phillip; Iavarone, Anthony T.; Jacobson, Matthew P.; Neau, David B.; Newcomer, Marcia; Holman, Theodore R.
  • ItemOpen Access
    Tau Induces Formation of α-synuclein Filaments with Distinct Molecular Conformations
    (2021) Dasari, Anvesh K. R.; Lim, Kwang Hun; Hojjatian, Alimohammad; Sengupta, Urmi; Taylor, Dianne; Daneshparvar, Nadia; Yeganeh, Fatemeh Abbasi; Dillard, Lucas; Michael, Brian; Griffin, Robert G.; Borgnia, Mario; Kayed, Rakez; Taylor, Kenneth A.
  • ItemOpen Access
    Study of Membrane Protein Monolayers Using Surface-Enhanced Infrared Absorption Spectroscopy (SEIRAS): Critical Dependence of Nanostructured Gold Surface Morphology
    (2021) Choe, Jun-Yong; Seiça, Ana; Iqbal, Muhammad Haseeb; Carvalho, Alain; Boulmedais, Fouzia; Hellwig, Petra
  • ItemOpen Access
    Identifcation of New GLUT2‑Selective Inhibitors Through in Silico Ligand Screening and Validation in Eukaryotic Expression Systems
    (2021) Iancu, Cristina V.; Choe, Jun-Yong; Schmidl, Sina; Ursu, Oleg; Oreb, Mislav; Oprea, Tudor I.