Characterization Of Protein Aggregation Using A Solid-State Nanopore Device,
2021
University of Arkansas, Fayetteville
Characterization Of Protein Aggregation Using A Solid-State Nanopore Device, Mitu Chandra Acharjee
Graduate Theses and Dissertations
Protein aggregation has been linked to many chronic and devastating neurodegenerative human diseases and is also strongly associated with aging. In the case of neurodegenerative diseases, α, β tubulins and tau proteins dissociate in a neuron cell and aggregate both intra and extra-cellularly. Tau and tubulin aggregations were found as one of the major causes of many neurodegenerative diseases, such as Parkinson’s, Picks, Alzheimer’s, Huntington, and Prion. Finding the state and mechanism of protein aggregation is significant. In this work, tau and tubulin aggregations were detected in ionic solutions using the solid-state nanopore technique. Besides tau and tubulin, aggregations of …
Lions, Tigers, And Hemes - Oh My! A Dynamic Look At The Electronic Effects Of Porphyrin Substitution On Cytochrome P450 Olet,
2021
University of South Carolina - Columbia
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 …
Biophysical Characterization Of The Par-4 Tumor Suppressor: Evidence Of Structure Outside The Coiled Coil Domain And Interactions With Platinum Chemotherapeutics,
2021
Old Dominion University
Biophysical Characterization Of The Par-4 Tumor Suppressor: Evidence Of Structure Outside The Coiled Coil Domain And Interactions With Platinum Chemotherapeutics, Andrea Megan Clark
Chemistry & Biochemistry Theses & Dissertations
Prostate apoptosis response-4 (Par-4) is an apoptosis-inducing tumor suppressor protein. Full-length Par-4 has previously been shown to be a predominantly intrinsically disordered protein (IDP) under neutral conditions, with significant regular secondary structure evident only within the C-terminal coiled coil domain. However, IDPs can gain ordered structure through the process of induced folding, which often occurs under non-neutral conditions. Previous work has shown that the Par-4 leucine zipper, which is a subset of the C-terminal coiled coil domain, is disordered under neutral conditions, but forms a dimeric coiled coil at acidic pH. Increase in ionic strength was also shown to increase …
Case 32: Inhibition Of Protein Tyrosine Phosphatase Enzymes As A Possible Treatment For Diabetes,
2021
Providence College
Case 32: Inhibition Of Protein Tyrosine Phosphatase Enzymes As A Possible Treatment For Diabetes, Dr. Kathleen Cornely
Chemistry & Biochemistry Case Studies
Protein tyrosine phosphatases (PTPs) are investigated because of their ability to reverse the effects of protein tyrosine kinases (PTKs). Inhibitors of the PTP investigated in this study have insulin-mimetic effects and have potential in the treatment of diabetes.
A Computational Investigation Of The Biophysical Mechanisms Underlying Thermotaxis In The Afd Neurons Of Caenorhabditis Elegans,
2021
Illinois State University
A Computational Investigation Of The Biophysical Mechanisms Underlying Thermotaxis In The Afd Neurons Of Caenorhabditis Elegans, Zachary Mobille
Theses and Dissertations
Thermotaxis in the nematode Caenorhabditis elegans (C. elegans) is studied at the cellular scale of the amphid finger-like ciliated (AFD) neurons, which have previously been shown to be essential for thermoreception. The voltage and calcium signals of AFD during temperature stimuli are described with ordinary differential equations. The primary calcium model is a modified version of that published by Kuramochi and Doi in 2017 to explain the calcium responses of the chemosensitive amphid single-ciliated right (ASER) neuron to fluctuations in extracellular salt concentration. To account for the effects of temperature, changes to the stimuli conditions under which inactivation takes place …
Case 70: Hemoglobin Mito: A Japanese Hemoglobin Variant With Altered Oxygen Binding Affinity,
2021
Providence College
Case 70: Hemoglobin Mito: A Japanese Hemoglobin Variant With Altered Oxygen Binding Affinity, Dr. Kathleen Cornely
Chemistry & Biochemistry Case Studies
In this case study, researchers use their knowledge of hemoglobin structure to predict the oxygen binding properties of a hemoglobin mutant with a single amino acid substitution, then test their hypothesis by studying the mutant’s oxygen binding properties.
Using The Marcus Inverted Region And Artificial Cofactors To Create A Charge Separated State In De Novo Designed Proteins,
2021
CUNY Graduate Center
Using The Marcus Inverted Region And Artificial Cofactors To Create A Charge Separated State In De Novo Designed Proteins, Eskil Me Andersen
Dissertations, Theses, and Capstone Projects
To create an efficient de novo photosynthetic protein it is important to create long lived charge separated states. Achieving stable charge separation leads to an increase in the efficiency of the photosynthetic reaction which in turn leads to higher yields of end products, such as biofuels, electrical charge, or synthetic chemicals. In an attempt to create charge separated states in de novo proteins we hypothesized that we could engineer the free energy gaps in the proteins from excited primary donor (PD) to acceptor (A), and A back to ground state PD such that the forward electron transfer (ET) would be …
The C. Neoformans Cell Wall: A Scaffold For Virulence,
2021
CUNY Graduate Center
The C. Neoformans Cell Wall: A Scaffold For Virulence, Christine Chrissian
Dissertations, Theses, and Capstone Projects
Cryptococcus neoformans is a globally distributed opportunistic fungal pathogen and the causative agent of life threatening cryptococcal meningoencephalitis in immunocompromised individuals, resulting in ~180,000 deaths each year worldwide. A primary virulence-associated trait of this organism is the production of melanin. Melanins are a class of diverse pigments produced via the oxidation and polymerization of aromatic ring compounds that have a characteristically complex, heterogenous, and amorphous structure. They are synthesized by representatives of all biological kingdoms and share a multitude of remarkable properties such as the ability to absorb ultraviolet (UV) light and protect against ionizing radiation. Melanin production in fungi …
Direct Recruitment Of Eif4gi And/Dap5 To The 5' Utr Of A Subset Of Human Mrna Drives Their Cap-Independent Translation,
2021
CUNY Graduate Center
Direct Recruitment Of Eif4gi And/Dap5 To The 5' Utr Of A Subset Of Human Mrna Drives Their Cap-Independent Translation, Solomon A. Haizel
Dissertations, Theses, and Capstone Projects
During unfavorable cellular conditions (e.g., tumor hypoxia, viral infection, nutrient deprivation, etc.), the canonical, cap-dependent translation initiation pathway in human cells is suppressed by sequestration of the cap-binding protein, eukaryotic initiation factor(eIF) 4E, by 4E-binding proteins. Circumvention of cap-dependent translation shutdown has been linked to tumor development and cancer progression. The stress-induced repression of cap-dependent translation has also been correlated with increased eIF4GI and its homolog, Death Associated Protein 5 (DAP5) expression levels, suggesting these factors have a role in cap-independent translation. Despite several evidence pointing towards a link upregulation of eIF4GI and /DAP5 levels during stress conditions, and the …
Third Harmonic Generation: A Method For Visualizing Myelin In The Murine Cerebral Cortex,
2021
CUNY Graduate Center
Third Harmonic Generation: A Method For Visualizing Myelin In The Murine Cerebral Cortex, Michael Redlich
Dissertations, Theses, and Capstone Projects
Here we present the use of Third Harmonic Generation (THG) for the label-free imaging of myelinated axons in the murine cerebral cortex. Myelin plays an important role in the processes of learning and disease. However, much of the myelin biology research thus far has focused on white matter tracts where myelin is more visible. Much is still unknown, particularly with regard to myelin in gray matter. First, we engage in THG microscopy using an optical parametric oscillator pumped by a titanium-sapphire laser to demonstrate the utility of the technique for imaging myelin in vivo. Second, we investigate the use of …
Uncovering The Roles And Evolved Sequence Grammar Of Hypervariable Intrinsically Disordered Proteins In Bacterial Cell Division,
2021
Washington University in St. Louis
Uncovering The Roles And Evolved Sequence Grammar Of Hypervariable Intrinsically Disordered Proteins In Bacterial Cell Division, Megan Cohan
McKelvey School of Engineering Graduate Student Theses & Dissertations
Across all domains of life, a defining hallmark of the onset of cell division is the formation of a cytokinetic ring at the center of the cell. Cell division is a tightly controlled process that involves various regulatory factors that modulate the assembly of the cytokinetic ring. In rod-shaped bacteria, the ring is termed the Z-ring after the protein FtsZ, which is foundational to ring formation and is the bacterial homolog of tubulin. Like tubulin, FtsZ is an assembling GTPase, where GTP binding promotes the cooperative assembly into FtsZ polymers that laterally associate to form bundles. While the GTPase domain …
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 …
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 …
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 …
Optimized Microbial Recombinant Production Of Hiv-1 Anti-Envelope Antibody Fragments With Applications To Single Particle Tracking Of Virus Assembly,
2021
University of Denver
Optimized Microbial Recombinant Production Of Hiv-1 Anti-Envelope Antibody Fragments With Applications To Single Particle Tracking Of Virus Assembly, Merissa Michelle Bruns
Electronic Theses and Dissertations
In my findings, I have established a set series of protocols to recombinantly produce, purify and apply various fluorescent probes in vitro for the fluorescent labeling and study of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) protein during HIV viral assembly. There remains insufficient knowledge about the molecular dynamics and interactions of HIV-1 Env protein with its counterpart, Gag, on the inner host cell surface during assembly of a mature virus particle. There also remains an insufficient amount of data for the understanding and clarification of the mechanism of action of a known host cell HIV-1 restriction factor, …
Simulation Of A Rat Muscle-Tendon Unit With Hill-Type Model Dynamics And The Study Of Viscoelasticity In A Collagen Molecule Via Molecular Dynamics,
2021
West Chester University
Simulation Of A Rat Muscle-Tendon Unit With Hill-Type Model Dynamics And The Study Of Viscoelasticity In A Collagen Molecule Via Molecular Dynamics, Veronica Siko
West Chester University Master’s Theses
The field of biological science has established that tendons transfer muscular forces to adjacent bones, but there is a dearth of information about the underlying physical principles of these interactions and how the property of viscoelasticity (displayed in tendons as a difference in mechanical response to stress with differing stretching rates) is encompassed in the collagen of tendons. This thesis details the results of concentric and eccentric contractions of the rat muscle-tendon unit (MTU) with and without viscoelasticity (concentric contraction requires active shortening of the muscle, while eccentric contraction requires active lengthening of the muscle) (Lovering & Brooks, 2014). Once …
Muscarinic Excitation Of Dopamine Neurons In The Ventral Tegmental Area Via Activation Of A Trpc-Like Cation Conductance,
2021
Virginia Commonwealth University
Muscarinic Excitation Of Dopamine Neurons In The Ventral Tegmental Area Via Activation Of A Trpc-Like Cation Conductance, Yu Tzu Chen
Theses and Dissertations
Dopaminergic (DA) neurons in the ventral tegmental area (VTA) play a crucial role in reward and motivational behaviors, including the development of drug addictions. VTA DA neurons receive excitatory cholinergic inputs from the mesopontine tegmentum. Blockage of the M5 muscarinic receptor in DA neurons has been shown to attenuate drug-induced DA release and abuse-related behaviors, but the molecular mechanism is unknown. In this study, experiments were designed to identify the electrophysiological effects of muscarinic agonism in the modulation of action potential kinetics and firing patterns in VTA DA neurons of mice. Pharmacology of the muscarinic receptor-evoked current was also characterized. …
Fxr Agonists Induce Distinct H-12 Structural States,
2021
University of Montana
Fxr Agonists Induce Distinct H-12 Structural States, Vikash Kumar
Graduate Student Theses, Dissertations, & Professional Papers
The nuclear receptor ligand-binding domain (LBD) is a highly dynamic entity. The FXR LBD shows multiple low-energy conformational states of the activation function-2 (AF-2) coregulator binding surface upon ligand binding, indicating the complexity of FXR activation. However, it is unknown how ligand binding leads to different conformational states within the AF-2 region centered on helix 12 (H-12) of the LBD. Here we observe the conformation of the coregulator binding surface (H-12 specifically) of FXR upon ligand binding in solution using fluorine-19 (19F) nuclear magnetic resonance (NMR) and simulations of this surface using molecular dynamics. Fluorescence anisotropy of fluorescein-labeled coregulator peptides …
Development And Clinical Validation Of Knowledge-Based Planning Models For Stereotactic Body Radiotherapy Of Early-Stage Non-Small-Cell Lung Cancer Patients,
2021
University of Kentucky
Development And Clinical Validation Of Knowledge-Based Planning Models For Stereotactic Body Radiotherapy Of Early-Stage Non-Small-Cell Lung Cancer Patients, Justin David Visak
Theses and Dissertations--Radiation Medicine
Lung stereotactic body radiotherapy (SBRT) is a viable alternative to surgical intervention for the treatment of early-stage non-small-cell lung cancer (NSCLC) patients. This therapy achieves strong local control rates by delivering ultra-high, conformal radioablative doses in typically one to five fractions. Historically, lung SBRT plans are manually generated using 3D conformal radiation therapy, dynamic conformal arcs (DCA), intensity-modulated radiation therapy, and more recently via volumetric modulated arc therapy (VMAT) on a C-arm linear accelerator (linac). Manually planned VMAT is an advanced technique to deliver high-quality lung SBRT due to its dosimetric capabilities and utilization of flattening-filter free beams to improve …
Study Of Primary Cilium Structure And Intraflagellar Transport,
2021
University at Albany, State University of New York
Study Of Primary Cilium Structure And Intraflagellar Transport, Shufeng Sun
Legacy Theses & Dissertations (2009 - 2024)
Primary cilia are hair-like protrusions that stem from the basal bodies in the cytoplasm and extend into the extracellular space to sense signals. Intraflagellar transport (IFT) functions to transport cargo molecules into and out of the ciliary compartment to assemble, maintain, and disassemble the cilia. Accurate knowledge of the three-dimensional (3D) structure of primary cilia and precise details of the IFT profile is the foundation for understanding the sensory functions of primary cilia. This work covers three aspects of primary cilia. Firstly, we obtained and analyzed the overall 3D architecture of the complete primary cilia axoneme region using serial section …
