Advanced Computational Methodologies To Study Binding Free Energies Of Biomolecular Complexes,
2020
CUNY Graduate Center
Advanced Computational Methodologies To Study Binding Free Energies Of Biomolecular Complexes, Rajat Kumar Pal
Dissertations, Theses, and Capstone Projects
Molecular recognition is the basis of biological mechanisms and is a key element to consider while formulating effective and safe drugs. Pharmaceutical drugs are designed so as to bind a target protein even at very low concentrations to alter the diseased conditions without interfering with normal biological processes. In a rational drug design process, this is achieved by acquiring information about the chemical structure and the physical and chemical properties of the target protein receptor to gain insights on how changing the chemical composition of the substrate drug could affect the protein-drug interaction and binding affinities. Computational models are used …
Case 34: Kinetics Of Alkaline Phosphatase,
2020
Providence College
Case 34: Kinetics Of Alkaline Phosphatase, Dr. Kathleen Cornely
Chemistry & Biochemistry Case Studies
Kinetic studies are carried out using the alkaline phosphatase, an enzyme that has an important role in skeletal mineralization.
Examining Artifacts Of The Watershed Segmentation,
2020
University of Denver
Examining Artifacts Of The Watershed Segmentation, Emily Jo Armitage
Electronic Theses and Dissertations
The watershed segmentation is an algorithm used to systematically track cell intercalary behaviors during germ band extension of the Drosophila embryo. Neighboring cells share a contracting vertical interface, called a T1, which continues contracting to a single point, a T2, and extending in the horizontal direction to create what is called a T3 interface (Fig. 1). Additionally, higher order vertices called rosettes occur when five or more cells meet at a common vertex. Simulated T2 events demonstrate that cell angle and not noise level in the image contributes to the incorrect detection of artifactual T1s in more acute angled cells …
Quantification Of Mitochondrial Zinc Homeostasis And Analysis Of Zinc And Polyamine-Mediated Axonal Trafficking,
2020
University of Denver
Quantification Of Mitochondrial Zinc Homeostasis And Analysis Of Zinc And Polyamine-Mediated Axonal Trafficking, Dylan Hunt Fudge
Electronic Theses and Dissertations
The zinc ion is an important emerging signaling molecule for biological processes. In this work we engineered improved zinc sensors based on our previously developed fluorescent sensor GZnP1 to provide sensors with a higher fluorescent readout, faster kinetics, and a superior sensitivity to zinc. We utilized these zinc sensors and further developed the sensors to answer questions pertaining to biological zinc. We showed the labile zinc concentration in the mitochondrial matrix was less than 1 pM while the labile zinc concentration in the cytosol and mitochondrial IMS were comparable (~100 pM) across four different cell lines. Using these zinc sensors …
Quantification Of Dynamic Epithelial Sheet Architecture In Botryllus Schlosseri Using 2-D & 3-D Image Analysis,
2020
University of Denver
Quantification Of Dynamic Epithelial Sheet Architecture In Botryllus Schlosseri Using 2-D & 3-D Image Analysis, Roopa Madhu
Electronic Theses and Dissertations
Epithelial tubules form critical structures in various body tissues; how- ever, since they are difficult to access experimentally, their architecture and dynamics are not well understood. Here we examine the dynamic remodeling of epithelial tubes in vivo using a novel and uniquely accessible model system: the extracorporeal vasculature of Botryllus schlosseri (sea squirt). In Botryllus, massive retraction of blood vessels can be triggered without loss of barrier function, through (i) disrupting collagen crosslinking in the basement membrane using β-aminopropionitrile (BAPN); or (ii) disrupting the integrin pathway through inhibition of focal adhesion kinase (FAK). We performed stereographic projections of 3-dimensional …
Cellular And Organismal Ramifications Of De Novo Purine Synthesis Dysregulation,
2020
University of Denver
Cellular And Organismal Ramifications Of De Novo Purine Synthesis Dysregulation, Randall Craig Mazzarino
Electronic Theses and Dissertations
Purines are a class of nitrogenous bases and are essential small molecules to life. Purines are used within the cell as genetic information carriers, energy currency, signaling molecules, and cofactors for multiple processes. They are formed through de novo and salvage pathways found in cells across the phylogenetic tree. The substrates of enzymes within de novo purine synthesis are known to influence other processes within the cell, such as energy homeostasis. In humans, de novo purine synthesis disorders are rare, with around 100 people identified. These patients exhibit a range of phenotypes, with varying degrees of mental retardation, seizure activity, …
Engineering Ph-Dependent Antibody Interactions Through Linked Protonation Events In Interdomain Interfaces,
2020
Northern Illinois University
Engineering Ph-Dependent Antibody Interactions Through Linked Protonation Events In Interdomain Interfaces, Hyeyoung Eom
Graduate Research Theses & Dissertations
Engineered antibodies are frequently used in life science applications, such as therapeutics and clinical diagnostics. These customized antibodies typically possess enhanced binding affinity and/or specificity, yet these interactions are only one-way binding events that cannot be easily controlled without extreme changes in conditions, such as pH, denaturant, and/or temperature that likely irreversible damage the antibody and antigen. Here, we explore the design of proton-linked binding events in the context of both antibody/hapten (i.e., a low molecular weight ligand target) and antibody/antigen complexes. Specifically, this work looks to overcome the challenges of engineering pH-dependent small ligand/protein interactions, as well as develop …
Single-Lipid Sorting And Dynamics At Nanoscale Membrane Curvatures: The Effects Of Fluorescence Labeling, Composition, Phase, And Temperature,
2020
Wayne State University
Single-Lipid Sorting And Dynamics At Nanoscale Membrane Curvatures: The Effects Of Fluorescence Labeling, Composition, Phase, And Temperature, Xinxin Woodward
Wayne State University Dissertations
Nanoscale membrane curvature on cell plasma membrane assists in the spatial organization and domain formation that are critical for life of eukaryotic cells. Lipids and proteins can sense, be sorted by, and generate both functional domains and membrane curvature. Reveal the relationship between membrane curvature, phase separation, and single-molecule behavior is a key to understanding fundamental processes, such as phagocytosis initiation, cell signaling, and membrane budding. Single lipid dynamic and sorting on engineered membrane curvature is studied to understand the effects of fluorescence labeling, composition, phase separation, and temperature. Single particle tracking was used to find radial averaged diffusion at …
Probing The Secondary Structure Of Intrinsically Disordered Squid Reflectin Protein Through Ssnmr,
2020
University of Central Florida
Probing The Secondary Structure Of Intrinsically Disordered Squid Reflectin Protein Through Ssnmr, Harriet Austin
Digital Repository: Showcase of Undergraduate Research Excellence
No abstract provided.
Complex Ciliary Flows Around Stentor Polymorphus In Solutions Of 2% Buttermilk And Chlamydomonas Reinhardtii,
2020
Scripps College
Complex Ciliary Flows Around Stentor Polymorphus In Solutions Of 2% Buttermilk And Chlamydomonas Reinhardtii, Eliana B. Smithstein
Scripps Senior Theses
Stentor are large, unicellular ciliates of the Heterotricha order. They live in both freshwater and marine habitats and are mostly found in ponds. I studied Stentor polymorphus, which is a species of Stentor only recently discovered to be lab culturable. They range from 0.5-1.5mm in length and are unusual because they live with endosymbiotic algae and are much more likely than other, more widely studied, species of Stentor to form aggregates while they are eating. There are three main components to this thesis: First, I established protocols for keeping a viable S. polymorphus culture, since no protocols had been …
Gravity-Drawing Flexible Silicone Filaments As Fiber Optics And Model Foldamers,
2020
Claremont Colleges
Gravity-Drawing Flexible Silicone Filaments As Fiber Optics And Model Foldamers, Katherine Snell
CMC Senior Theses
Here, we present a method of gravity-drawing polydimethylsiloxane (PDMS) silicone fibers with application as fiber optics and as model foldamers. Beginning as a viscous liquid, PDMS is cured using heat until its measured viscosity reaches 4000 mPa•s. The semi-cured elastomer is then extruded through a tube furnace to produce thin (diameters on the order of hundred micrometers) filaments with scalable lengths. PDMS is biocompatible, gas-permeable, flexible, and hydrophobic. Additionally, the PDMS surface hydrophobicity can be modified via UV exposure, O2 plasma, and corona discharge. We demonstrate the patternibility (i.e patterns of hydrophobicity) of PDMS fibers, adding complexity to potential foldamer …
Acoustic Analysis Of Nomascus Gibbon Songs As A Potential Measure Of Current Health Status,
2020
Central Washington University
Acoustic Analysis Of Nomascus Gibbon Songs As A Potential Measure Of Current Health Status, Caroline Rowley
All Master's Theses
Post-release monitoring is vital to the rehabilitation process. Gibbons offer a unique challenge, as they are notoriously difficult to follow through the forest, but their duets offer a non-invasive window into their lives. The aim of this project is to create a method that will evaluate the health of rehabilitated and released gibbons through acoustic analyses. Gibbon duets are in part genetically determined, but learning may play a role in song development. Additionally, songs may indicate resource holding potential, and are vital to acquiring mates and producing offspring. Captive-raised gibbons are often denied the experience of co-singing with their parents, …
Deconvolution Tools For Extracting Insight From Challenging Two-Flavin Systems,
2020
University of Kentucky
Deconvolution Tools For Extracting Insight From Challenging Two-Flavin Systems, Dallas Michael Bell
Theses and Dissertations--Chemistry
Flavoproteins have long been explored for their ubiquity among a number of metabolic and energetic reactions. The flavin cofactor has the inherent benefit of distinct spectral changes associated with redox transitions; however, the double-edged sword is incurred as these distinct signatures overlap and take up much of the UV-vis spectral range. Therefore, it is crucial to create a method to demarcate the expressed redox transitions for studying these systems. The first portion of these studies discusses the creation of a program that deduces spectra for redox transitions in a single-flavin containing model protein: flavodoxin. The latter portions discuss the application …
Synthesis And Biophysical Analysis Of The Cell-Penetrating Peptide Penetratin And Its Aromatic Analogues,
2020
Wilfrid Laurier University
Synthesis And Biophysical Analysis Of The Cell-Penetrating Peptide Penetratin And Its Aromatic Analogues, An Le
Theses and Dissertations (Comprehensive)
Cell-penetrating peptides (CPPs) interact with biological membranes, undergo cellular intake/uptake, and may act as potential drug delivery agents. Understanding the molecular interactions of these peptides with membranes contributes to gaining a better knowledge of their potential use in medical and pharmaceutical applications to improve human health. The current research focuses on understanding the mechanisms of a CPP in interaction with different model phospholipid membranes. The peptide penetratin (primary sequence: RQIKIWFQNRRMKWKK) is an example of a CPP that can interact with and pass through biological membranes. The current thesis provides spectroscopic and calorimetric evidence that penetratin associates with lipid membranes. Circular …
A Novel Pool Of Microparticle Cholesterol Is Elevatedin Rheumatoid Arthritis But Not In Systemic Lupus Erythematosus Patients,
2020
Technological University Dublin
A Novel Pool Of Microparticle Cholesterol Is Elevatedin Rheumatoid Arthritis But Not In Systemic Lupus Erythematosus Patients, Shuai Shuai Hu, Brenton L. Cavanagh, Robert Harrington, Muddassar Ahmad, Grainne Kearns, Steve Meaney, Claire Wynne
Articles
Microparticles are sub-micron, membrane-bound particles released from virtually allcells and which are present in the circulation. In several autoimmune disorders their amountand composition in the circulation is altered. Microparticle surface protein expression has beenexplored as a differentiating tool in autoimmune disorders where the clinical pictures can overlap.Here, we examine the utility of a novel lipid-based marker—microparticle cholesterol, present in allmicroparticles regardless of cellular origin—to distinguish between rheumatoid arthritis (RA) andsystemic lupus erythematosus (SLE). We first isolated a series of microparticle containing lipoproteindeficient fractions from patient and control plasma. There were no significant differences in thesize, structure or protein content of …
Special Issue On The Third Workshop On Biological Mentality,
2020
Michigan Technological University
Special Issue On The Third Workshop On Biological Mentality, Kenneth A. Augustyn
Michigan Tech Publications, Part 1
The Third Workshop on Biological Mentality was held from September 23, 2019 to March 2, 2020 as a series of twenty-one Monday online conferencing sessions, each consisting of a talk followed by a Q&A discussion. Like the two previous workshops [1, 2], the objective of this workshop was to seek a deeper level of understanding the physical foundations of biological mentality (whether conscious or nonconscious).
Factors Influencing Huntingtin Aggregation At Surfaces: Implications For Huntington’S Disease,
2020
West Virginia University
Factors Influencing Huntingtin Aggregation At Surfaces: Implications For Huntington’S Disease, Sharon E. Groover
Graduate Theses, Dissertations, and Problem Reports (ETD)
Huntington’s Disease (HD) is a genetic, neurodegenerative disease characterized by an abnormal polyglutamine (polyQ) expansion in the first exon of the huntingtin protein (htt). The polyQ domain facilitates aggregation and initiates the formation of a diverse collection of aggregate species, including fibrils, oligomers and annular aggregates. The first 17 amino acids of htt (Nt17) directly flank the polyQ domain and is a key factor in htt’s association to membranous structures. In addition to Nt17 being an amphipathic αhelix, it also promotes aggregation through self-association and contains numerous posttranslational modifications (PTMs) that can modulate toxicity and subcellular localization. For in depth …
The Effects Of Membrane Physicochemical Properties On Huntingtin Membrane Association And Downstream Aggregation,
2020
West Virginia University
The Effects Of Membrane Physicochemical Properties On Huntingtin Membrane Association And Downstream Aggregation, Maryssa Beasley
Graduate Theses, Dissertations, and Problem Reports (ETD)
Huntington’s Disease (HD) is a fatal neurodegenerative disorder caused by an expanded glutamine repeat region (polyQ) within the huntingtin protein (htt). As a result of the expanded polyQ domain, htt associates into a variety of toxic aggregate species. The polyQ domain of htt is flanked at the N-terminal end by 17 amino acids (Nt17) that adopt an amphipathic α-helical structure in the presence of binding partners such as lipid membranes. In addition to comprising a lipid binding domain, the Nt17 amphipathic α -helix has been directly implicated in htt aggregation initiation via self-association with other Nt17 α -helices. Due to …
Amyloid Proteins And Fibrils Stability,
2019
New Jersey Institute of Technology
Amyloid Proteins And Fibrils Stability, Farbod Mahmoudinobar
Dissertations
Compared to globular proteins that have a stable native structure, intrinsically disordered peptides (IDP) sample an ensemble of structures without folding into a native conformation.One example of IDP is the amyloid-beta(Abeta) protein which is the main constituent of senile plaques in the brain of Alzheimer's patients.Understanding the process by which IDPs undergo structural changes to form oligomers that eventually aggregate into senile plaques/amyloid fibrils may significantly advance the development of novel therapeutic methods to treat neurodegenerative diseases, for which there is no cure to date. This dissertation has two main objectives. The first one is to investigate and identify structural …
Engineering Hyaluronic Acid For Biomedical Applications,
2019
University of Nebraska Medical Center
Engineering Hyaluronic Acid For Biomedical Applications, Deep S. Bhattacharya
Theses & Dissertations
This work presents research using the naturally available non- sulfated carbohydrate glycosaminoglycan hyaluronic acid (HA) for the synthesis of different chemical derivatives of HA for evaluation of binding kinetics with CD44 and P- selectin proteins for applications in fluorescence image-guided surgery. Chemical derivatives of HA such as deacetylated HA (deHA), sulfated HA (sHA), and deacetylated and sulfated HA (s-deHA) were synthesized by modulating sulfating and deacetylating reagents to alter binding specificities to CD44. Modified HA derivatives and CD44 biophysical interactions were assessed by fluorescence polarization. In silico techniques were also used to determine binding using molecular docking and MM-PBSA approaches. …
