Experimental And Computational Observations Of Immunogenic Cobalt Porphyrin Lipid Bilayers: Nanodomain-Enhanced Antigen Association.,
2021
Western University
Experimental And Computational Observations Of Immunogenic Cobalt Porphyrin Lipid Bilayers: Nanodomain-Enhanced Antigen Association., Jasmin Federizon, Conrard Giresse Tetsassi Feugmo, Wei-Chiao Huang, Xuedan He, Kazutoyo Miura, Aida Razi, Joaquin Ortega, Mikko Karttunen, Jonathan F Lovell
Chemistry Publications
Cobalt porphyrin phospholipid (CoPoP) can incorporate within bilayers to enable non-covalent surface-display of antigens on liposomes by mixing with proteins bearing a polyhistidine tag (his-tag); however, the mechanisms for how this occurs are poorly understood. These were investigated using the his-tagged model antigen Pfs25, a protein antigen candidate for malaria transmission-blocking vaccines. Pfs25 was found to associate with the small molecule aquocobalamin, a form of vitamin B12 and a cobalt-containing corrin macrocycle, but without particle formation, enabling comparative assessment. Relative to CoPoP liposomes, binding and serum stability studies indicated a weaker association of Pfs25 to aquocobalamin or cobalt nitrilotriacetic acid …
Design Of Fibril Forming Collagen Mimetic Peptides: Heterotrimers And Nucleation Domains,
2021
CUNY Hunter College
Design Of Fibril Forming Collagen Mimetic Peptides: Heterotrimers And Nucleation Domains, Sally Tan
Theses and Dissertations
This paper attempts to design collagen mimetic peptides where the triple-helical region mimics that of human Type I Collagen. With consideration for chain selection and chain register, we utilize the NC2 domain of heterotrimeric Type IX Collagen as a nucleation domain for triple-helix folding.
Arginase 1 Insufficiency Precipitates Amyloid-Β Deposition And Hastens Behavioral Impairment In A Mouse Model Of Amyloidosis,
2021
University of Kentucky
Arginase 1 Insufficiency Precipitates Amyloid-Β Deposition And Hastens Behavioral Impairment In A Mouse Model Of Amyloidosis, Chao Ma, Jerry B. Hunt, Maj-Linda B. Selenica, Awa Sanneh, Leslie A. Sandusky-Beltran, Mallory Watler, Rana Daas, Andrii Kovalenko, Huimin Liang, Devon Placides, Chuanhai Cao, Xiaoyang Lin, Michael B. Orr, Bei Zhang, John C. Gensel, David J. Feola, Marcia N. Gordon, Dave Morgan, Paula C. Bickford, Daniel C. Lee
Sanders-Brown Center on Aging Faculty Publications
Alzheimer’s disease (AD) includes several hallmarks comprised of amyloid-β (Aβ) deposition, tau neuropathology, inflammation, and memory impairment. Brain metabolism becomes uncoupled due to aging and other AD risk factors, which ultimately lead to impaired protein clearance and aggregation. Increasing evidence indicates a role of arginine metabolism in AD, where arginases are key enzymes in neurons and glia capable of depleting arginine and producing ornithine and polyamines. However, currently, it remains unknown if the reduction of arginase 1 (Arg1) in myeloid cell impacts amyloidosis. Herein, we produced haploinsufficiency of Arg1 by the hemizygous deletion in myeloid cells using Arg1 …
Discovery Of Small Molecules Targeting The Tandem Tudor Domain Of The Epigenetic Factor Uhrf1 Using Fragment-Based Ligand Discovery,
2021
The Texas Medical Center Library
Discovery Of Small Molecules Targeting The Tandem Tudor Domain Of The Epigenetic Factor Uhrf1 Using Fragment-Based Ligand Discovery, Lyra Chang, James Campbell, Idris O Raji, Shiva K R Guduru, Prasanna Kandel, Michelle Nguyen, Steven Liu, Kevin Tran, Navneet K Venugopal, Bethany C Taylor, Matthew V Holt, Nicolas L Young, Errol L G Samuel, Prashi Jain, Conrad Santini, Banumathi Sankaran, Kevin R Mackenzie, Damian W Young
Faculty, Staff and Students Publications
Despite the established roles of the epigenetic factor UHRF1 in oncogenesis, no UHRF1-targeting therapeutics have been reported to date. In this study, we use fragment-based ligand discovery to identify novel scaffolds for targeting the isolated UHRF1 tandem Tudor domain (TTD), which recognizes the heterochromatin-associated histone mark H3K9me3 and supports intramolecular contacts with other regions of UHRF1. Using both binding-based and function-based screens of a ~ 2300-fragment library in parallel, we identified 2,4-lutidine as a hit for follow-up NMR and X-ray crystallography studies. Unlike previous reported ligands, 2,4-lutidine binds to two binding pockets that are in close proximity on TTD and …
Central Nervous System Intravascular Lymphoma Leading To Rapidly Progressive Dementia,
2021
The Texas Medical Center Library
Central Nervous System Intravascular Lymphoma Leading To Rapidly Progressive Dementia, Christie G Turin, Kevin Ting, Anthony Bradshaw, S Richard Dunham, Karen Nunez-Wallace, Shital M Patel, Priti Dangayach, Stephanie Holdener, Weei-Chin Lin
Faculty, Staff and Students Publications
Intravascular lymphoma is an uncommon subtype of B-cell lymphoma with neoplastic cells limited to the lumen of small blood vessels. We report a case of a 52-year-old man who presented with constitutional symptoms and rapidly progressive dementia. He was found to have diffuse leptomeningeal and faint parenchymal enhancement on magnetic resonance imaging and was subsequently diagnosed with intravascular lymphoma following a brain biopsy. He responded remarkably well to systemic and intrathecal chemotherapy. The diagnosis and treatment of intravascular lymphoma have been guided by a few case reports and are largely based on expert opinion.
Self-Assembled Thermoresponsive Nanogel From Grafted Hyaluronic Acid As A Biocompatible Delivery Platform For Curcumin With Enhanced Drug Loading And Biological Activities,
2021
University of South Carolina
Self-Assembled Thermoresponsive Nanogel From Grafted Hyaluronic Acid As A Biocompatible Delivery Platform For Curcumin With Enhanced Drug Loading And Biological Activities, Jittima Amie Luckanagul, Pahweenvaj Ratnatilaka Na Bhuket, Chawanphat Muangnoi, Pranee Rojsitthisak, Qian Wang, Pornchai Rojsitthisak
Faculty Publications
A hyaluronic acid-grafted poly(N-isopropylacrylamide) (HA-pNIPAM) was synthesized as a polymeric nanogel platform for encapsulation and delivery of hydrophobic bioactive compounds using curcumin as a model drug. As demonstrated by transmission electron microscopy and dynamic light scattering techniques, the HA-pNIPAM was simply assembled into spherical nano-sized particles with the thermoresponsive behavior. The success of curcumin aqueous solubilization was confirmed by fluorescent spectroscopy. The resulting nanogel formulation enhanced the aqueous solubility and uptake into NIH-3T3 cells of curcumin. This nanogel formulation also demonstrates cytocompatibility against NIH-3T3 cells, which deems it safe as a delivery vehicle. Moreover, the formulation has a slight skin-protection …
Single-Cell Fluidic Force Microscopy Reveals Stress- Dependent Molecular Interactions In Yeast Mating,
2021
UCLouvain
Single-Cell Fluidic Force Microscopy Reveals Stress- Dependent Molecular Interactions In Yeast Mating, Marion Mathelié-Guinlet, Felipe Viela, JéRôMe Dehullu, Sviatlana Filimonava, Jason M. Rauceo, Peter N. Lipke, Yves F. DufrêNe
Publications and Research
Sexual agglutinins of the budding yeast Saccharomyces cerevisiae are proteins mediating cell aggregation during mating. Complementary agglutinins expressed by cells of opposite mating types “a” and “α” bind together to promote agglutination and facilitate fusion of haploid cells. By means of an innovative single-cell manipulation assay combining fluidic force microscopy with force spectroscopy, we unravel the strength of single specific bonds between a- and α-agglutinins (~100 pN) which require pheromone induction. Prolonged cell–cell contact strongly increases adhesion between mating cells, likely resulting from an increased expression of agglutinins. In addition, we highlight the critical role of disulfide bonds of the …
Potential Counter Regulatory Effects Of A Gut Microbiota Metabolite In Alleviating Down-Regulation Krüppel-Like Factor 4 In Intestinal Inflammation,
2021
Marshall University
Potential Counter Regulatory Effects Of A Gut Microbiota Metabolite In Alleviating Down-Regulation Krüppel-Like Factor 4 In Intestinal Inflammation, Ylva Forslund
Theses, Dissertations and Capstones
Inflammatory bowel disease (IBD) is a medical condition characterized by chronic inflammation of the intestinal epithelium. Krüppel-like factor 4 (KLF4), a zinc finger transcription factor, is vital for maintaining intestinal epithelial homeostasis. KLF4 promotes differentiation of goblet cells that generate the protective mucus layer. Reduced goblet cell number and defective mucus layer are associated with IBD. Shortchain fatty acids (SCFA) are known to play an important role in the maintenance of a strong and healthy intestinal epithelial layer and also in goblet cell differentiation. However, whether the positive effects of SCFAs on goblet cells are mediated, at least partly, via …
The Effects Of Endocrine Disrupting Chemicals On Plants,
2021
Marshall University
The Effects Of Endocrine Disrupting Chemicals On Plants, Christian Mathew Pridemore
Theses, Dissertations and Capstones
Endocrine disrupting chemicals (EDCs) are a diverse group of chemicals which can have a detrimental effect on human health, affecting any physiological body system sensitive to hormonal changes. Human exposure to EDCs is inevitable due to their prevalence in modern living; EDCs are integral compounds found in everyday items with which humans interact and ingest. These, along with other indirect avenues leading to EDC exposure, pose a threat to both human health and to the health of wildlife and agricultural environments. Studies on the effects of EDCs on plants can be substantially informative and necessary for progress towards solving the …
Potential Drug Treatment For Duchenne Muscular Dystrophy Which Could Be Through Upregulation Of Lipin1,
2021
Wright State University
Potential Drug Treatment For Duchenne Muscular Dystrophy Which Could Be Through Upregulation Of Lipin1, Rajsi Y. Thaker
Browse all Theses and Dissertations
Duchenne muscular dystrophy (DMD) is a genetic disorder leading to progressive muscle degeneration and weakness due to mutation in dystrophin gene, which is very important for maintaining muscle membrane integrity. Dystrophin is the largest gene in the human genome therefore more prone to mutation. There is currently no cure for DMD. Our lab recently found that Lipin1 deficient myofibers showed upregulation of necroptosis correlated with the loss of muscle membrane integrity. Our primary approach for ameliorating dystrophic phenotype in DMD is through reduction of necroptosis using drugs which can potentially upregulate Lipin1 expression. In this study, we identified two drugs …
Quantitated Effects Of Nutritional Supplementation On Exercise Induced Sweat,
2021
Wright State University
Quantitated Effects Of Nutritional Supplementation On Exercise Induced Sweat, Andrew Blake Austin Browder
Browse all Theses and Dissertations
Discovery studies have identified many metabolites contained in human sweat. However, quantitative analysis of the sweat metabolome content remains mostly unknown. Furthermore several attributes, including rate, have been defined to affect sweat metabolite content, while other effectors, like diet, remain unknown. This study works to quantitatively define the metabolite impact caused by nutritional supplementation. To better understand the effect diet plays, a LC-MS method was developed focusing on improving resolution and peak width. While the literature provided examples of how diet affected sweat metabolite concentrations, the long-term effects of diet have not been explored. The experiment described here attempts to …
Root Nrt, Nir, Amt, Gs, Gogat
And Gdh Expression Levels Reveal
No Andaba Mediated Drought
Tolerance In Brassica Juncea L.,
2021
Jamia Millia Islamia University
Root Nrt, Nir, Amt, Gs, Gogat And Gdh Expression Levels Reveal No Andaba Mediated Drought Tolerance In Brassica Juncea L., Seema Sahay, Luis Robledo-Arratia, Katarzyna Glowacka, Meetu Gupta
Department of Biochemistry: Faculty Publications
Little is known about the interactive effects of exogenous nitric oxide (NO) and abscisic acid (ABA) on nitrogen (N) metabolism and related changes at molecular and biochemical levels under drought stress. The present study highlights the independent and combined effect of NO and ABA (grouped as “nitrate agonists”) on expression profiles of representative key genes known to be involved in N-uptake and assimilation, together with proline metabolism, N–NO metabolism enzyme’s activity and nutrient content in polyethylene glycol (PEG) treated roots of Indian mustard (B. juncea cv. Varuna). Here we report that PEG mediated drought stress negatively inhibited growth performance, as …
Modeling Disorder In Proteins Yields Insights Into The Evolution Of Stability And Function,
2021
University of Denver
Modeling Disorder In Proteins Yields Insights Into The Evolution Of Stability And Function, Jonathan Huihui
Electronic Theses and Dissertations
The central dogma of molecular biology dictates that a DNA sequence codes for an RNA sequence, which in turn codes for a sequence of amino acids that comprises a protein. Proteins are responsible with performing myriad functions within living organisms and most proteins require a folded structure in order to perform their function. The protein's structure is the direct link from sequence to function. This is known as the sequence - structure - function paradigm. However, this does not mean that the unfolded state is unimportant. In order to properly model the stability of the folded state, one needs to …
Notch Regulates Vascular Collagen Iv Basement Membrane Through Modulation Of Lysyl Hydroxylase 3 Trafficking,
2021
University of Denver
Notch Regulates Vascular Collagen Iv Basement Membrane Through Modulation Of Lysyl Hydroxylase 3 Trafficking, Stephen J.B. Gross
Electronic Theses and Dissertations
Collagen type IV (Col IV) is a basement membrane protein associated with early blood vessel morphogenesis and is essential for blood vessel stability. Defects in vascular Col IV deposition are the basis of heritable disorders, such as small vessel disease, marked by cerebral hemorrhage and drastically shorten lifespan. To date, little is known about how endothelial cells regulate the intracellular transport and selective secretion of Col IV in response to angiogenic cues, leaving a void in our understanding of this process. Our aim was to identify trafficking pathways that regulate Col IV deposition during angiogenic blood vessel development. We have …
Development Of Endoplasmic Reticulum Targeted Probes And Red Fluorescent Probes For Detecting Zinc,
2021
University of Denver
Development Of Endoplasmic Reticulum Targeted Probes And Red Fluorescent Probes For Detecting Zinc, Drew Maslar
Electronic Theses and Dissertations
Zinc (Zn2+) is the second most abundant transition metal in the body and is important in various biological functions. Fluorescent sensors based on circularly permuted fluorescent proteins (cpFPs) have been previously made to detect labile, or unbound, Zn2+ within the cytoplasm of cells. These sensors have proven invaluable for studying Zn2+, however, these sensors are limited to their use in the cytoplasm and by the fact that only green cpFP have been utilized to create fluorescent Zn2+ sensors. In this thesis, we use a combination of peptide targeting sequences, site-directed mutagenesis, and rational design …
Validation Of A Deployable Proteomic Assay For The Serological Screening Of Sexual Assault Samples,
2021
University of Denver
Validation Of A Deployable Proteomic Assay For The Serological Screening Of Sexual Assault Samples, Catherine O'Sullivan Brown
Electronic Theses and Dissertations
Protein mass spectrometry (MS) has emerged as a technique to supplant traditional serological tests for body fluid identification. It was hypothesized that proteomic techniques would surpass the sensitivity and specificity of traditional serological techniques. An automated workflow coupled with protein MS has been developed for the confirmatory identification of five biological fluids. A developmental validation was completed, assessing parameters such as reproducibility, sensitivity, ion suppression, and limit of detection. Implementation was determined through tandem sample processing by MS, traditional serological tests, and standard DNA profiling methods. The MS approach offered superior detection limits while also providing true confirmatory results, producing …
Nucleic Acids Promote Oligomerization Of Immunoglobulin G,
2021
University of Denver
Nucleic Acids Promote Oligomerization Of Immunoglobulin G, Alexa Gomez
Electronic Theses and Dissertations
Nucleic acids have been found to prevent aggregation as chaperones, as well as act as co-factors and promote aggregation of amyloidogenic proteins leading to various diseases. Immunoglobulin G, IgG, are prone to aggregate as therapeutic proteins, and light chains of IgG can form amyloid fibrils, causing a disease known as light chain amyloidosis. Here we discuss the effect nucleic acids have on full-length immunoglobulin G aggregation. Our results show G-quadruplex DNA, and bulk DNA lead to oligomerization of full-length IgG, and induce increases in secondary structure. Tryptophan fluorescence indicates structural changes are occurring in the presence of DNA. Additionally, IgG …
Characterization Of The Whale Shark (Rhincodon Typus) Melanocortin-2 Receptor,
2021
University of Denver
Characterization Of The Whale Shark (Rhincodon Typus) Melanocortin-2 Receptor, Brianne Hoglin
Electronic Theses and Dissertations
Among bony vertebrates, the melanocortin-2 receptor ortholog is unique among the family of five melanocortin receptors on the basis that it is dependent on its accessory protein, MRAP1, for trafficking and activation, and is selective for activation by ACTH alone. Previous studies on the MC2R orthologs of select cartilaginous fish, the elephant shark (Callorhinchus milii) and the red stingray (Dasyatis akajei), revealed divergent traits in a less obligatory relationship on MRAP1 and its ability to be activated by ACTH or the MSH-sized peptides. However, observed traits were not consistent between these two cartilaginous fish species, posing …
A Biophysical Investigation Of Hiv-1 Envelope Cytoplasmic-Tail Mediated Retention In The Gag Lattice,
2021
University of Denver
A Biophysical Investigation Of Hiv-1 Envelope Cytoplasmic-Tail Mediated Retention In The Gag Lattice, Nicholas Scott Groves
Electronic Theses and Dissertations
The infectivity of Human Immunodeficiency Virus is critically dependent on successful incorporation of the trimeric viral envelope glycoprotein, Envelope (Env), into Gag lattice assembly sites on the host-cell plasma membrane during virus biogenesis. The mechanistic nature of interaction between Gag, the structural protein, and Env, the viral spike, are dependent on the Gag matrix (MA) and Env cytoplasmic tail (CT) domains. Env laterally diffuses on the host cell plasma membrane until encountering a budding Gag lattice, where it is retained until particle scission and release. The mechanism of Env entry and retention in the lattice remains elusive and enigmatic. Here …
Molecular Dynamics Simulations Of A Metal/Ligand Complex,
2021
Calvin University
Molecular Dynamics Simulations Of A Metal/Ligand Complex, Plinio Rosales Lopez, Fenton Lawler, Ryan Storteboom, Douglas A. Vander Griend
Summer Research
Molecular Dynamics (MD) is a computer simulation method to analyze and study the physical movement of atoms and molecules in an environment constrained by physical and quantum mechanics laws. The systems that were of interest during this summer were metal/ligand complexes, also known as a coordination complex. A coordination complex consists of a central atom or ion, which in this case is a metal, and an array of bound molecules that are called the ligands. The ligand of interest for this summer is ethylenediamine. Both copper(II) and nickel(II) coordinate to ethylenediamine.
