Agonist-Induced Conformational Changes In The Nmda Receptor,
2021
The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences
Agonist-Induced Conformational Changes In The Nmda Receptor, Ryan Durham, Ryan Durham
Dissertations and Theses (Open Access)
NMDA receptors are ligand-gated ion channels that mediate a number of physiological and pathological phenomena within the mammalian central nervous system. Under the typical course of activation, these receptors bind to glycine and glutamate molecules and undergo a series of conformational changes that results in the opening of a cation-permeable pore in the neuronal plasma membrane. Various aspects of NMDA receptor function are not fully understood, including the phenomenon of negative cooperativity between the glycine- and glutamate-binding sites of the receptor and the mechanism controlling partial agonism. Past studies utilizing static structural snapshots of the receptor or isolated domains of …
Relative Success Of Native Plants In Curb Cut Rain Gardens,
2021
Calvin University
Relative Success Of Native Plants In Curb Cut Rain Gardens, Ana Singh, Rachel Warners, Jonathan Walt, Patrick Jonker, David P. Warners
Faculty and Professional Research
No abstract provided.
Molecular Mechanism Of Dna Bisintercalator Antibiotic Resistance,
2021
University of Texas at El Paso
Molecular Mechanism Of Dna Bisintercalator Antibiotic Resistance, Priyanka Rajendra Gade
Open Access Theses & Dissertations
Class II UvrA is an ATP-binding cassette protein and a homolog of class I UvrA, the DNA lesion detection component of the universal prokaryotic nucleotide excision repair system. We show that Ecm16, a class II UvrA protein from Streptomyces lasalocidi, specifically recognizes DNA duplex that contains the DNA bisintercalator antibiotic echinomycin. Heterologous expression of Ecm16 in Escherichia coli renders host cells resistant to echinomycin. Interestingly, Ecm16’s antibiotic resistance activity does not require the DNA repair proteins UvrA/B/C/D, indicating that it operates independently of the cell’s nucleotide excision repair pathway. Unlike UvrA, Ecm16 uses the insertion domain to regulate its ATPase …
Investigating Effects Of Microenvironmental Stress On Cell Metabolism Using Multiphoton Imaging,
2021
University of Arkansas, Fayetteville
Investigating Effects Of Microenvironmental Stress On Cell Metabolism Using Multiphoton Imaging, Lisa Rebello
Graduate Theses and Dissertations
Resistance to therapy in cancer is a major cause of poor prognosis in patients. Tumor hypoxia plays an active role in mediating treatment resistance and has been linked to metastases and metastatic potential in cancer. Our research focused on three objectives: i) To understand metabolic effects of chronic and intermittent hypoxia in murine breast cancer cells and its affiliation with metastatic potential ii) To identify the metabolic changes associated with radiation therapy in a panel of radiosensitive and radioresistant human head and neck cancer cells and iii) to monitor the changes in cell metabolism associated with gain of treatment resistance. …
Impact Of Pank1 Deletion On Mitochondrial Acetylation And Cardiac Function During Pressure Overload.,
2021
University of Louisville
Impact Of Pank1 Deletion On Mitochondrial Acetylation And Cardiac Function During Pressure Overload., Timothy N. Audam
Electronic Theses and Dissertations
Recent studies have associated elevated protein acetylation levels with heart failure in humans. Although mechanisms promoting elevated acetylation levels are not fully known, excess acetyl-CoA may drive enzyme-independent acetylation of cardiac proteins. Accumulation of acetyl-CoA depends on the availability of sufficient CoA, whose production is regulated by pantothenate kinases in the CoA biosynthetic pathway. We show that cardiac proteins are hyperacetylated during heart failure in humans and tested in mice whether limiting CoA abundance would improve ventricular remodeling during pressure overload-induced hypertrophy. We limited cardiac CoA levels by deleting the rate-limiting enzyme in CoA biosynthesis, Pank1 (one of three PANK-encoding …
Mechanisms Of Stress Survival In Gram Positive Bacterial Pathogens,
2021
Old Dominion University
Mechanisms Of Stress Survival In Gram Positive Bacterial Pathogens, Asia Poudel
Chemistry & Biochemistry Theses & Dissertations
Anaerobic Gram-positive bacteria are not a well-characterized group but include many human pathogens that are resilient against stresses caused by the human immune system or by antibiotic treatment. This dissertation investigated the survival mechanisms of two clinically relevant Gram-positive organisms, Clostridioides difficile and Cutibacterium acnes under extracellular stresses. The response of the opportunistic skin pathogen Cutibacterium acnes to nanosecond electric pulses is characterized and found that growth in a biofilm, which usually protects bacteria from stress, renders this species more killable by this treatment. In addition, the stringent response (SR), a conserved bacterial stress survival mechanism, is studied in the …
The Flavoprotein Rcla Is A Hypothiocyanous Acid Reductase,
2021
Western Michigan University
The Flavoprotein Rcla Is A Hypothiocyanous Acid Reductase, Irina Chapman
Masters Theses
Reactive chlorine species (RCS) - hypochlorous acid (HOCl), hypothiocyanous acid (HOSCN), and chloramines - are powerful antimicrobial oxidants generated by the innate immune system. Bacteria developed defense mechanisms against RCS, which are highly toxic for invading pathogens. One such defense system involves RclA, an enzyme from the flavin disulfide reductase family, which is massively upregulated upon exposure of Escherichia coli to RCS. Recent research suggests that RclA functions as a Cu(II) reductase to provide resistance against RCS. However, the exact mechanism used by RclA was subject to debate. In this study, we demonstrate that RclA is unlikely to function as …
Effects Of Localized Oxygen Production By Electrolysis On The First-Generation Glucose Sensor Response,
2021
University of Arkansas, Fayetteville
Effects Of Localized Oxygen Production By Electrolysis On The First-Generation Glucose Sensor Response, Nandita Halder
Graduate Theses and Dissertations
Glucose sensors are very important for detecting blood glucose both in vitro and in vivo. First-generation glucose biosensors were based on the glucose oxidase (GOx) enzyme using molecular oxygen as the electron acceptor and therefore oxygen dependent. Unfortunately for in-vivo work, oxygen in the body is variable and limited. Alternative approaches to overcome the oxygen dependency came with their own limitations. The widely used and commercially available ex-vivo glucose test strip uses a mediator in place of oxygen to free it from oxygen dependency. The mediator-based technology, in most cases cannot be transferred to in vivo applications due to the …
Engineering Fluorescently Labeled Human Fibroblast Growth Factor One Mutants And Characterizing Their Photophysics Properties Towards Designing Fret Assays,
2021
University of Arkansas, Fayetteville
Engineering Fluorescently Labeled Human Fibroblast Growth Factor One Mutants And Characterizing Their Photophysics Properties Towards Designing Fret Assays, Mamello Mohale
Graduate Theses and Dissertations
Human fibroblast growth factor one (hFGF1) belongs to a family of 22 FGF members produced by fibroblast cells. Cell signaling during physiological processes of angiogenesis and wound healing occurs when hFGF1 binds to its receptor (FGFR). However, when heterogenous homeostasis is not maintained, fibroblast cells exhibit excessive proliferation which can lead to a myriad of cancers. smFRET is an ultrasensitive distant dependent (1-10 nm) technique capable of resolving such heterogeneity in structural dynamics and binding affinities (Kd). Therefore, we successfully designed and characterized fluorescently labeled hFGF1 tracers which span the visible light region of the electromagnetic spectrum for use in …
Site-Specific Effects Of Lysine Acetylation On Aminoacyl-Trna Synthetase,
2021
University of Arkansas, Fayetteville
Site-Specific Effects Of Lysine Acetylation On Aminoacyl-Trna Synthetase, Hao Chen
Graduate Theses and Dissertations
Aminoacyl-tRNA synthetases (AARSs) are an ancient and highly conserved family of enzymes which can catalyze a two-steps aminoacylation reaction to charge tRNAs with their cognate amino acids, thus playing crucial roles in ribosomal protein synthesis. Naturally, the accurate amino acids and tRNA recognition of these synthetases are essential to the fidelity of translation process. To assure the correct recognition, some of these synthetases have evolved with an editing function to help remove the mischarged tRNAs. In addition to these functions, AARSs are also involved in various biological processes ranging from transcription to translation. Currently, a series of proteomic studies have …
Genetically Engineered Thermosynechococcus Elongatus Bp1: Assessment Of Potential Biorisks And Biofuel Production,
2021
Old Dominion University
Genetically Engineered Thermosynechococcus Elongatus Bp1: Assessment Of Potential Biorisks And Biofuel Production, Thu Ho Anh Nguyen-Jones
Chemistry & Biochemistry Theses & Dissertations
According to the International Energy Outlook 2019, released by the U.S. Energy Information Administration, it is projected that the energy consumption will increase up to 50% between 2018 and 2050 worldwide. As fossil fuel being a finite source of energy with the risk of depletion, many countries are now facing an energy security crisis. Therefore, it is important to develop other renewable and sustainable energy sources that will allow countries to shift away from depending on fossil fuels. Among several types of renewable energy, biofuel production using genetically engineered cyanobacteria is capturing much interest due to its many advantages. Different …
Elucidation Of The Cellular Mechanisms Underlying Missense Mutations In Low Density Lipoprotein Receptor Related Protein 6 (Lrp6) Associated With Cardiovascular Diseases,
2021
United Arab Emirates University
Elucidation Of The Cellular Mechanisms Underlying Missense Mutations In Low Density Lipoprotein Receptor Related Protein 6 (Lrp6) Associated With Cardiovascular Diseases, Huda Issa Samha
Theses
Low-density Lipoprotein Receptor Related Protein 6 (LRP6) is a member of the Low-Density Lipoprotein Receptors family (LDLRs) which is involved in the clearance of LDL from the bloodstream and the signaling of the canonical wingless signaling pathway. Several genetic variants in the LRP6 gene have been conclusively associated with cardiovascular diseases (CVDs) and metabolic syndrome. However, the structural and functional implications of those variations have not been fully elucidated. The CVD-associated LRP6 variants could be retained and possibly subjected to Endoplasmic Reticulum Associated Degradation (ERAD), a quality control and adaptive process employed by cells to eliminate misfolded proteins to maintain …
Structure Of A Monomeric Photosystem Ii Core Complex From A Cyanobacterium Acclimated To Far-Red Light Reveals The Functions Of Chlorophylls D And F,
2021
Yale University
Structure Of A Monomeric Photosystem Ii Core Complex From A Cyanobacterium Acclimated To Far-Red Light Reveals The Functions Of Chlorophylls D And F, Christopher J. Gisriel, Gaozhong Shen, Ming-Yang Ho, Vasily Kurashov, David A. Flesher, Jimin Wang, William H. Armstrong, John H. Golbeck, Marilyn R. Gunner, David J. Vinyard, Richard J. Debus, Gary W. Brudvig, Donald A. Bryant
Publications and Research
Far-red light (FRL) photoacclimation in cyanobacteria provides a selective growth advantage for some terrestrial cyanobacteria by expanding the range of photosynthetically active radiation to include far-red/near-infrared light (700–800 nm). During this photoacclimation process, photosystem II (PSII), the water:plastoquinone photooxidoreductase involved in oxygenic photosynthesis, is modified. The resulting FRL-PSII is comprised of FRL-specific core subunits and binds chlorophyll (Chl) d and Chl f molecules in place of several of the Chl a molecules found when cells are grown in visible light. These new Chls effectively lower the energy canonically thought to define the “red limit” for light required to drive photochemical …
Stabilin Receptors Clear Lps And Control Systemic Inflammation,
2021
University of Nebraska–Lincoln
Stabilin Receptors Clear Lps And Control Systemic Inflammation, Fatima Cabral, Mustafa Al-Rahem, John Skaggs, Thushara A. Thomas, Naresh Kumar, Qian Wu, Paolo Fadda, Lianbo Yu, John M. Robinson, Jonghan Kim, Ekta Pandey, Xinghui Sun, Wael N. Jarjour, Murugesan V.S. Rajaram, Edward N. Harris, Latha P. Ganesan
Department of Biochemistry: Faculty Publications
Lipopolysaccharides (LPSs) cause lethal endotoxemia if not rapidly cleared from blood circulation. Liver sinusoidal endothelial cells (LSEC) systemically clear LPS by unknown mechanisms. We discovered that LPS clearance through LSEC involves endocytosis and lysosomal inactivation via Stabilin-1 and 2 (Stab1 and Stab2) but does not involve TLR4. Cytokine production was inversely related to clearance/endocytosis of LPS by LSEC. When exposed to LPS, Stabilin double knockout mice (Stab DK) and Stab1 KO, but not Stab2 KO, showed significantly enhanced systemic inflammatory cytokine production and early death compared with WT mice. Stab1 KO is not significantly different from Stab DK in circulatory …
Snake Venom Peptides And Toxin Targeting The Main Protease Of Sars-Cov-2,
2021
Kennesaw State University
Snake Venom Peptides And Toxin Targeting The Main Protease Of Sars-Cov-2, Breauna Strawder, James Stewart, Mohammad A. Halim
Symposium of Student Scholars
The corona virus began to spread in Wuhan, China which caused it to spread worldwide creating a global pandemic in the beginning of 2020, infecting over 243 million and killing over 4.5 million people worldwide. Significant efforts were made to produce vaccines against the virus, which led the recognition of a few vaccines that has been approved by FDA. These vaccines, Pfizer-BioNTech, Moderna and Johnson & Johnson, which all have efficacy against Covid-19. Despite having vaccines, COVID-19 is still present and infecting millions and killing thousands of people every day. Multiple therapeutic options would allow us to slow down or …
Binding Affinity And Interaction Of Sars-Cov-2 Epitopes With Major Histocompatibility Complex,
2021
Kennesaw State University
Binding Affinity And Interaction Of Sars-Cov-2 Epitopes With Major Histocompatibility Complex, Sareena Kandavalli, James Stewart, Mohammed A. Halim
Symposium of Student Scholars
SARS CoV-2 has been affecting the world since 2019. It caused 245 million cases of infection and around 5 million deaths worldwide. The most important strategies for the development of vaccines against SARS-CoV-2 are inactivated or weakened virus, replicating or non-replicating viral vector-based approaches, DNA, RNA, virus particle like approaches and epitope-based approaches. The epitope-based approach is rapid, accurate, cost-effective, and reliable against pathogens. By presenting epitopes (antigen peptides) on antigen-presenting cells (APCs), the major histocompatibility complex (MHC), also recognized as the human leukocyte antigen (HLA) system in humans, plays an essential role in triggering T-cell immune responses. The focus …
Cell Penetrating Peptide Inhibiting The Main Protease Of Sars-Cov-2,
2021
Kennesaw State University
Cell Penetrating Peptide Inhibiting The Main Protease Of Sars-Cov-2, Adam Ashley, James Stewart, Mohammad Halim
Symposium of Student Scholars
As of October 2021, SARS-CoV-2 has infected over 244 million people and killed about 5 million people. The current FDA approved vaccines are effective; however, they lose their effectiveness after a few months of receiving both doses of the vaccine, and it is recommended to get a booster shot six months after receiving the second dose of the vaccine. Therefore, new highly effective, long lasting antiviral agents and strategies are needed to create an alternative treatment for SARS-CoV-2 and the different variants. Previous studies have shown that cell penetrating peptides (CPPs) have led to greater efficiency of intracellular delivery. However, …
3-Dimensional Structural Determination Of Epidermal Growth Factor-Like Repeat 27 From Mouse Notch1 Using Nuclear Magnetic Resonance Spectroscopy,
2021
Louisiana State University
3-Dimensional Structural Determination Of Epidermal Growth Factor-Like Repeat 27 From Mouse Notch1 Using Nuclear Magnetic Resonance Spectroscopy, Justin Grennell
LSU Doctoral Dissertations
NOTCH1 has been associated with a variety of human ailments, such as cancer and heart disease. NOTCH1 is a transmembrane protein that contains 36 epidermal growth factor-like (EGF) repeats, which facilitate cell signaling by binding proteins on neighboring cells. Each repeat contains about 40 amino acids and has to be folded in a specific manner to function properly. The amino acid sequence, carbohydrate pattern, and calcium-binding sites of EGF-like repeats vary, but the pattern along the 36-repeat chain is conserved. The Abruptex region (EGF24-29) of NOTCH1 is a highly glycosylated (having undergone sugar addition) and flexible region, which gained its …
Aerobic Copper-Promoted Oxidative Dehydrosulfurative Carbon-Oxygen Cross-Coupling Of 3,4-Dihydropyrimidine-1: H -2-Thiones With Alcohols,
2021
Chungnam National University
Aerobic Copper-Promoted Oxidative Dehydrosulfurative Carbon-Oxygen Cross-Coupling Of 3,4-Dihydropyrimidine-1: H -2-Thiones With Alcohols, Jihong Lee, Yujeong Kwon, Dong-Chan Lee, Jeong Hun Sohn
Chemistry and Biochemistry Faculty Research
An aerobic Cu-promoted oxidative dehydrosulfurative carbon-oxygen cross-coupling of 3,4-dihydropyrimidin-1H-2-thiones (DHPMs) with both aliphatic and aromatic alcohols is described. Together with the ready availability of DHPMs and both alcohols, the method furnishes facile access to biologically valuable 2-alkoxypyrimidines with rapid diversification.
Bisindolylmaleimide Ix: A Novel Anti-Sars-Cov2 Agent Targeting Viral Main Protease 3clpro Demonstrated By Virtual Screening Pipeline And In-Vitro Validation Assays,
2021
Infectious Diseases, Mayo Clinic
Bisindolylmaleimide Ix: A Novel Anti-Sars-Cov2 Agent Targeting Viral Main Protease 3clpro Demonstrated By Virtual Screening Pipeline And In-Vitro Validation Assays, Yash Gupta, Dawid Maciorowski, Samantha E. Zak, Krysten A. Jones, Rahul S. Kathayat, Saara-Anne Azizi, Raman Mathur, Catherine M. Pearce, David J. Ilc, Hamza Husein, Andrew S. Herbert, Ajay Bharti, Brijesh Rathi, Ravi Durvasula, Daniel P. Becker, Bryan C. Dickinson, John M. Dye, Prakasha Kempaiah
Chemistry: Faculty Publications and Other Works
SARS-CoV-2, the virus that causes COVID-19 consists of several enzymes with essential functions within its proteome. Here, we focused on repurposing approved and investigational drugs/compounds. We targeted seven proteins with enzymatic activities known to be essential at different stages of the viral cycle including PLpro, 3CLpro, RdRP, Helicase, ExoN, NendoU, and 2′-O-MT. For virtual screening, energy minimization of a crystal structure of the modeled protein was carried out using the Protein Preparation Wizard (Schrodinger LLC 2020-1). Following active site selection based on data mining and COACH predictions, we performed a high-throughput virtual screen of drugs and investigational molecules (n = …
