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Altering Oligomerization Of Epha2 Via Mutations In The Intracellular Domain, Ryan W. Lingerak 2018 The University of Akron

Altering Oligomerization Of Epha2 Via Mutations In The Intracellular Domain, Ryan W. Lingerak

Honors Research Projects

Eph receptor tyrosine kinases (RTKs) are activated by membrane-bound ligands called ephrins. Eph RTKs are divided into two subclasses, each activated by a specific classes of the ligand ephrin. The overexpression of Eph receptors is correlated to cancer cell metastasis in several different types of cancers. Studies with the EphA2 extracellular domain (ECD) and ephrinA1 ligand have shown that upon binding of ephrin to the receptor, EphA2 undergoes increased oligomerization and activation. This indicates that oligomerization is intimately connected to kinase activity. High resolution crystal structures of the EphA2 ECD have revealed some details of these ligand bound oligomers, as ...


Protein Loop Dynamics Are Complex And Depend On The Motions Of The Whole Protein, Michael T. Zimmermann, Robert L. Jernigan 2017 Iowa State University

Protein Loop Dynamics Are Complex And Depend On The Motions Of The Whole Protein, Michael T. Zimmermann, Robert L. Jernigan

Robert Jernigan

We investigate the relationship between the motions of the same peptide loop segment incorporated within a protein structure and motions of free or end-constrained peptides. As a reference point we also compare against alanine chains having the same length as the loop. Both the analysis of atomic molecular dynamics trajectories and structure-based elastic network models, reveal no general dependence on loop length or on the number of solvent exposed residues. Rather, the whole structure affects the motions in complex ways that depend strongly and specifically on the tertiary structure of the whole protein. Both the Elastic Network Models and Molecular ...


Factors Correlating With Significant Differences Between X-Ray Structures Of Myoglobin, Alexander A. Rashin, Marcin J. Domagalski, Michael T. Zimmermann, Wladek Minor, Maksymilian Chruszcz, Robert L. Jernigan 2017 BioChemComp Inc

Factors Correlating With Significant Differences Between X-Ray Structures Of Myoglobin, Alexander A. Rashin, Marcin J. Domagalski, Michael T. Zimmermann, Wladek Minor, Maksymilian Chruszcz, Robert L. Jernigan

Robert Jernigan

Validation of general ideas about the origins of conformational differences in proteins is critical in order to arrive at meaningful functional insights. Here, principal component analysis (PCA) and distance difference matrices are used to validate some such ideas about the conformational differences between 291 myoglobin structures from sperm whale, horse and pig. Almost all of the horse and pig structures form compact PCA clusters with only minor coordinate differences and outliers that are easily explained. The 222 whale structures form a few dense clusters with multiple outliers. A few whale outliers with a prominent distortion of the GH loop are ...


Protein Flexibility: Coordinate Uncertainties And Interpretation Of Structural Differences, Alexander A. Rashin, Abraham H. L. Rashin, Robert L. Jernigan 2017 BioChemComp Inc

Protein Flexibility: Coordinate Uncertainties And Interpretation Of Structural Differences, Alexander A. Rashin, Abraham H. L. Rashin, Robert L. Jernigan

Robert Jernigan

Valid interpretations of conformational movements in protein structures determined by X-ray crystallography require that the movement magnitudes exceed their uncertainty threshold. Here, it is shown that such thresholds can be obtained from the distance difference matrices (DDMs) of 1014 pairs of independently determined structures of bovine ribonuclease A and sperm whale myoglobin, with no explanations provided for reportedly minor coordinate differences. The smallest magnitudes of reportedly functional motions are just above these thresholds. Uncertainty thresholds can provide objective criteria that distinguish between true conformational changes and apparent `noise', showing that some previous interpretations of protein coordinate changes attributed to external ...


The Behavior Response Of Antlion Larvae To Alternating Magnetic Fields, Lindsey Wagner, Caleb L. Adams 2017 Radford University

The Behavior Response Of Antlion Larvae To Alternating Magnetic Fields, Lindsey Wagner, Caleb L. Adams

Annual Symposium on Biomathematics and Ecology: Education and Research

No abstract provided.


Bacterial Motility And Its Role In Biofilm Formation, Clayton J. Culp, Arezoo M. Ardekani, Adib Ahmadzadegan 2017 Purdue University

Bacterial Motility And Its Role In Biofilm Formation, Clayton J. Culp, Arezoo M. Ardekani, Adib Ahmadzadegan

The Summer Undergraduate Research Fellowship (SURF) Symposium

Bacterial biofilms are known to cause millions of dollars in damage in the medical industry per year via infection of central venous catheters, urinary catheters, and mechanical heart valves. Unfortunately, there are some characteristics of biofilm formation that are yet to be fully understood. Recently much work has been done to investigate the motility characteristics of bacteria with hopes of better understanding the phenomena of biofilm formation. Still, one of the least understood stages is bacterial attachment or adhesion, a process designed to anchor bacteria in an advantageous environment. Providing a better understanding of bacterial motility near solid interfaces will ...


The Effect Of Hemodynamic Force On The Maturation Of Blood Vessels During Embryogenesis, Rachel Lee Padget 2017 Missouri State University

The Effect Of Hemodynamic Force On The Maturation Of Blood Vessels During Embryogenesis, Rachel Lee Padget

MSU Graduate Theses

Throughout embryonic development, blood vessels are derived from endothelial cells by way of vasculogenesis. During angiogenesis, vessels remodel to form a hierarchy of large-diameter arteries that branch into small-diameter capillaries. In this maturation, vessels respond to unidentified signaling events to become surrounded with an outer layer of vascular smooth muscle cells (vSMCs). This results in arteries that have a thick vSMC layer, veins that have a thin vSMC layer, and capillaries that have a very thin or absent vSMC layer. What remains to be determined is the cause of the thicker layer of vSMCs around proximal arteries. Previous studies have ...


Experiment-Based Quantitative Modeling For The Antibacterial Activity Of Silver Nanoparticles, Mohammad Aminul Haque 2017 University of Arkansas, Fayetteville

Experiment-Based Quantitative Modeling For The Antibacterial Activity Of Silver Nanoparticles, Mohammad Aminul Haque

Theses and Dissertations

Silver (Ag) has been well known for its antimicrobial activity for a long time. Recent research showed the potential of Ag nanoparticles as emerging antimicrobial agents. However, little quantitative analysis has been performed so far to decipher the mechanism of interaction between nanoparticles and bacteria. Here, a detailed analysis based on kinetic growth assay and colony forming unit assay has been carried out to study the antimicrobial effect of Ag nanoparticles against Escherichia coli (E. coli) bacteria. It was observed that the presence of Ag nanoparticles increased the lag time of bacterial growth while not affecting the maximum growth rate ...


Elucidating Mechanisms Of Protein Aggregation In Alzheimer’S Disease Using Antibody-Based Strategies., Benjamin A. Colvin 2017 University of Missouri - St. Louis

Elucidating Mechanisms Of Protein Aggregation In Alzheimer’S Disease Using Antibody-Based Strategies., Benjamin A. Colvin

Dissertations

Alzheimer’s Disease (AD) is a devastating neurodegenerative disorder. There are two characteristic histopathological hallmarks in the brain: senile plaques and neurofibrillary tangles, composed of insoluble aggregates of the amyloids Amyloid-β (Aβ) and tau protein, respectively. These diagnostic markers, though distinctive, are not apparent effectors of AD pathology. Evidence has mounted suggesting smaller soluble aggregates (oligomers) of Aβ or tau are the true drivers of disease progression. This dissertation presents several amyloid biophysics projects. Aggregate biophysical parameters such as weight, shape, and conformation were measured using a range of methodologies, including Multiangle Light Scattering, Dynamic Light Scattering, UV-Circular Dichroism, UV-Fluorescence ...


Capacitive Memory Alters Alternans And Spontaneous Activity In A Minimal Cardiomyocyte Model, Tien Comlekoglu, Seth H. Weinberg 2017 Virginia Commonwealth University

Capacitive Memory Alters Alternans And Spontaneous Activity In A Minimal Cardiomyocyte Model, Tien Comlekoglu, Seth H. Weinberg

Biology and Medicine Through Mathematics Conference

No abstract provided.


Tissue Damage Quantification In Alzheimer's Disease Brain Via Magnetic Resonance Gradient Echo Plural Contrast Imaging (Gepci), Yue Zhao 2017 Washington University in St. Louis

Tissue Damage Quantification In Alzheimer's Disease Brain Via Magnetic Resonance Gradient Echo Plural Contrast Imaging (Gepci), Yue Zhao

Arts & Sciences Electronic Theses and Dissertations

Alzheimer’s disease (AD) affected approximately 48 million people worldwide in 2015. Its devastating consequences have stimulated an intense search for AD prevention and treatment. Clinically, AD is characterized by memory deficits and progressive cognitive impairment, leading to dementia. Over the past two to three decades, researchers have found that amyloidbeta (Aβ) plaques and neurofibrillary tau tangles occur during a long pre-symptomatic period (preclinical stage) before the onset of clinical symptoms. As a result, identification of the preclinical stage is essential for the initiation of prevention trials in asymptomatic individuals. Currently, Positron Emission Tomography (PET) imaging with injected 11C or ...


Physical Principles Governing Colloidal Particle Deposition At Low Reynold’S Number: Applications To Microbial Biofilms, Sophia Wiedmann 2017 Macalester College

Physical Principles Governing Colloidal Particle Deposition At Low Reynold’S Number: Applications To Microbial Biofilms, Sophia Wiedmann

Macalester Journal of Physics and Astronomy

Biofilms formed from the adhesion of microbes to a surface hold great relevance to public health and wastewater management. However, the physical principles underlying the attachment stage of biofilm formation, when individual microbes first come into contact with a substrate, are not well understood. Here I report on a model of colloidal particle attachment to a surface that incorporates the effects of diffusion, advection, gravity, and the hydrodynamic lift and drag forces experienced by polystyrene beads at low Reynold’s number. The simulation predicts attachment rates of 1.04x10^(-8)m/s, 0.73x10^(-8)m/s, and 1.29x10 ...


Fret-Based Investigations Of The Structure-Function Relationships In The Nmda Receptor, Drew M. Dolino 2017 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Fret-Based Investigations Of The Structure-Function Relationships In The Nmda Receptor, Drew M. Dolino

UT GSBS Dissertations and Theses (Open Access)

The N-methyl-D-aspartate (NMDA) receptor is one member of a class of proteins known as the ionotropic glutamate receptors. Ionotropic glutamate receptors mediate the majority of excitatory neurotransmission in the central nervous system, with the NMDA receptor standing out among these receptors for its requirement of a co-agonist, its magnesium-block-based coincidence detection, its slow kinetics, its calcium permeability, its allosteric modulation, and its especially important functional roles in synaptic plasticity, excitotoxicity, and more. In recent years, a wealth of structural information has come about describing endpoint structures to high resolution, but such structures are unable to fully resolve the movements ...


Mechanisms Of Acid And Base Secretion: Implications For Airway Host Defense In Cystic Fibrosis, Viral Shailesh Shah 2017 University of Iowa

Mechanisms Of Acid And Base Secretion: Implications For Airway Host Defense In Cystic Fibrosis, Viral Shailesh Shah

Theses and Dissertations

The airway surface contains a number of important defense mechanisms to protect against infection. Antimicrobials found in the thin layer of fluid lining the airways, the airway surface liquid (ASL), rapidly kill bacteria. Another defense mechanism, mucociliary transport, propels foreign particles and mucus out of the airways. These and potentially other host defense properties show a dependence on the pH of the ASL. An acidic ASL pH reduces bacterial killing by cationic antimicrobial peptides, and increases ASL viscosity, potentially effecting mucociliary transport. Consequently, an acidic ASL pH can impair airway host defense.

An example of a disease where an acidic ...


Oxidative Quenching Of Photoexcited Ru(Ii)-Bipyridine Complexes By Oxygen, Danielle Rebecca Latham 2017 East Tennessee State University

Oxidative Quenching Of Photoexcited Ru(Ii)-Bipyridine Complexes By Oxygen, Danielle Rebecca Latham

Undergraduate Honors Theses

An experimental approach was taken in determining the quantum yield of Ruthenium(II) with Oxygen using two different Ru complexes. This reaction results in Ruthenium(III) and O2-. The Coulombic interactions caused by a carboxylate functional was found to increase the yield of charge separation. This was done using a diode to measure the intensity of the completed reaction over a certain time frame. The intensities were turned into concentrations. The concentration over time was used to determine the quantum yield. This information is useful in creating more efficient light emitting diodes.


Characterization Of The Rnap Binding Sites On A Λ Dna Using A Solid State Nanopore Combined With A Tuning Fork Force Sensing Probe Tip, Harpreet Kaur 2017 University of Arkansas, Fayetteville

Characterization Of The Rnap Binding Sites On A Λ Dna Using A Solid State Nanopore Combined With A Tuning Fork Force Sensing Probe Tip, Harpreet Kaur

Theses and Dissertations

In this dissertation, the binding positions of RNAP holoenzyme on a λ DNA are characterized using an apparatus that integrates a Solid State Nanopore with a Tuning Fork based Force sensing probe (SSN-TFFSP). The SSN-TFFSP system combines the measurement of ionic current through a solid-state nanopore with a DNA tethered probe tip. The position of the tip is sensed by a tuning fork force sensor and is controlled with a nanopositioning system. With this apparatus, translocation speed of DNA through solid state nanopores has been brought down to 100 μs/base. Such a controlled movement of DNA through a solid ...


Investigation Of Membrane Receptors’ Oligomers Using Fluorescence Resonance Energy Transfer And Multiphoton Microscopy In Living Cells, Ashish K. Mishra 2017 University of Wisconsin-Milwaukee

Investigation Of Membrane Receptors’ Oligomers Using Fluorescence Resonance Energy Transfer And Multiphoton Microscopy In Living Cells, Ashish K. Mishra

Theses and Dissertations

Investigating quaternary structure (oligomerization) of macromolecules (such as proteins and nucleic acids) in living systems (in vivo) has been a great challenge in biophysics, due to molecular diffusion, fluctuations in several biochemical parameters such as pH, quenching of fluorescence by oxygen (when fluorescence methods are used), etc.

We studied oligomerization of membrane receptors in living cells by means of Fluorescence (Förster) Resonance Energy Transfer (FRET) using fluorescent markers and two photon excitation fluorescence micro-spectroscopy. Using suitable FRET models, we determined the stoichiometry and quaternary structure of various macromolecular complexes. The proteins of interest for this work are : (1) sigma-1 receptor ...


Plateau Potential Fluctuations And Intrinsic Membrane Noise, Daniel Scott Borrus 2017 College of William and Mary

Plateau Potential Fluctuations And Intrinsic Membrane Noise, Daniel Scott Borrus

Undergraduate Honors Theses

This thesis focuses on subthreshold membrane potential fluctuations in the plateau potentials of bistable neurons. Research involved with plateau potentials typically finds one of the resting membrane potentials to be more susceptible to voltage fluctuations. This difference in the amplitude of the membrane potential fluctuations is most often attributed to the voltage-dependent membrane conductance. Occasionally, however, the typically quieter resting membrane potential exhibits larger voltage fluctuations than the expected one. It has been proposed that this increased membrane potential noise is the result of the stochastic gating of the voltage-gated ion channels. In this thesis, we use a simple bistable ...


Influence Of Histidine Residues, Ph And Charge Interactions On Membrane-Spanning Peptides, Ashley N. Henderson 2017 University of Arkansas, Fayetteville

Influence Of Histidine Residues, Ph And Charge Interactions On Membrane-Spanning Peptides, Ashley N. Henderson

Theses and Dissertations

Designed transmembrane peptides were employed for investigations of histidine residues within the hydrophobic environment of the lipid bilayer by means of oriented solid-state deuterium NMR spectroscopy. Using the model peptide GWALP23 sequence (GGALW(LA)6LWLAGA) as a host framework, the effects of single and double histidine mutations were explored. Replacement of leucine residue 12 to polar neutral histidine had little influence on the peptide average orientation, however under strongly acidic pH conditions in DOPC bilayers, the histidine becomes positively charged (pKa 2.5) and the GWALP23-H12 peptide exits the membrane and adopts a surface-bound orientation. Conversely, mutation of leucine 14 ...


Using Fluorescence Microscopy To Identify A Potential New Treatment For Heart Failure, Ryan D. Himes 2017 Olivet Nazarene University

Using Fluorescence Microscopy To Identify A Potential New Treatment For Heart Failure, Ryan D. Himes

Scholar Week 2016 - present

Cardiac glycosides have been used to treat heart failure for centuries, but they have a narrow therapeutic window, as they inhibit their target receptor nearly irreversibly. Overdoses can lead to arrhythmias. Phospholemman is a natural inhibitor of the same target as cardiac glycosides. It is possible that mutating phospholemman could achieve the same therapeutic benefit, while allowing cells to reverse the inhibition and thereby avoid an arrhythmia. I used fluorescence microscopy to screen candidate phospholemman mutants and identify one that binds more avidly to its target than the naturally occurring phospholemman. This mutant, L30A, caused similar effects as cardiac glycosides ...


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