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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 ...


Exploring Ground-State Heterogeneity Of Hypericin And Hypocrellin A And B:  Dynamic And 2d Roesy Nmr Study, Alexandre V. Smirnov, D. Bruce Fulton, Amy H. Andreotti, Jacob W. Petrich 2017 Iowa State University

Exploring Ground-State Heterogeneity Of Hypericin And Hypocrellin A And B:  Dynamic And 2d Roesy Nmr Study, Alexandre V. Smirnov, D. Bruce Fulton, Amy H. Andreotti, Jacob W. Petrich

Amy Andreotti

A NMR study was conducted on the antiviral and antitumor agents hypericin and hypocrellin A and B, whose activity is light induced. Elucidation of the conformational/tautomeric properties of these polycyclic quinones is important for interpreting their photophysical behavior in the excited state. Evidence for interconversion between ground-state tautomers or other conformational isomers was sought in temperature-dependent 1H NMR and 2D-ROESY studies. For hypericin and hypocrellin B, only one ground-state species is observed. For hypocrellin A, however, three species are significantly populated in the ground state due to the high flexibility of its 7-membered ring. In the latter case dynamic ...


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 ...


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.


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 ...


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 ...


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 ...


Hydration Site Of Cyclophilin A And Its Allosteric Effects On The Enzyme's Function, Abdullah Shouaib, Jonathan Lopez 2017 Georgia State University

Hydration Site Of Cyclophilin A And Its Allosteric Effects On The Enzyme's Function, Abdullah Shouaib, Jonathan Lopez

Georgia State Undergraduate Research Conference

No abstract provided.


Novel Isotopic Labeling Strategy For Nucleic Acids: Less Is More, sarah v. nguyen 2017 Georgia State University

Novel Isotopic Labeling Strategy For Nucleic Acids: Less Is More, Sarah V. Nguyen

Georgia State Undergraduate Research Conference

No abstract provided.


Computing Spatiotemporal Heat Maps Of Lipid Electropore Formation: A Statistical Approach, Willy Wriggers, Frederica Castellani, Julio A. Kovacs, P. Thomas Vernier 2017 Old Dominion University

Computing Spatiotemporal Heat Maps Of Lipid Electropore Formation: A Statistical Approach, Willy Wriggers, Frederica Castellani, Julio A. Kovacs, P. Thomas Vernier

Mechanical & Aerospace Engineering Faculty Publications

We extend the multiscale spatiotemporal heat map strategies originally developed for interpreting molecular dynamics simulations of well-structured proteins to liquids such as lipid bilayers and solvents. Our analysis informs the experimental and theoretical investigation of electroporation, that is, the externally imposed breaching of the cell membrane under the influence of an electric field of sufficient magnitude. To understand the nanoscale architecture of electroporation, we transform time domain data of the coarse-grained interaction networks of lipids and solvents into spatial heat maps of the most relevant constituent molecules. The application takes advantage of our earlier graph-based activity functions by accounting for ...


A Balanced Approach To Adaptive Probability Density Estimation, Julio Kovacs, Cailee Helmick, Willy Wriggers 2017 Old Dominion University

A Balanced Approach To Adaptive Probability Density Estimation, Julio Kovacs, Cailee Helmick, Willy Wriggers

Mechanical & Aerospace Engineering Faculty Publications

Our development of a Fast (Mutual) Information Matching (FIM) of molecular dynamics time series data led us to the general problem of how to accurately estimate the probability density function of a random variable, especially in cases of very uneven samples. Here, we propose a novel Balanced Adaptive Density Estimation (BADE) method that effectively optimizes the amount of smoothing at each point. To do this, BADE relies on an efficient nearest-neighbor search which results in good scaling for large data sizes. Our tests on simulated data show that BADE exhibits equal or better accuracy than existing methods, and visual tests ...


Calibrated Brightfield-Based Imaging For Measuring Intracellular Protein Concentration, Nathan Mudrak, Priyanka S. Rana, Michael A. Model 2017 Kent State University - Kent Campus

Calibrated Brightfield-Based Imaging For Measuring Intracellular Protein Concentration, Nathan Mudrak, Priyanka S. Rana, Michael A. Model

Undergraduate Research Symposium

Intracellular protein concentration is an essential cell characteristic which manifests itself through the refractive index. The latter can be measured from two or more mutually defocused brightfield images analyzed using the TIE (transport-of-intensity equation). In practice, however, TIE does not always achieve quantitatively accurate results on biological cells. Therefore, we have developed a calibration procedure that involves successive imaging of cells in solutions containing different amounts of added protein. This allows one to directly relate the output of TIE (T) to intracellular protein concentration C (g/l). The resultant relationship has a simple form: C ≈ 1.0(T/V), where ...


The Role Of Pyruvate Dehydrogenase And Acetyl-Coenzyme A Synthetase In Fatty Acid Synthesis In Developing Arabidopsis Seeds, Jinshan Ke, Robert H. Behal, Stephanie L. Back, Basil J. Nikolau, Eve S. Wurtele, David J. Oliver 2017 Iowa State University

The Role Of Pyruvate Dehydrogenase And Acetyl-Coenzyme A Synthetase In Fatty Acid Synthesis In Developing Arabidopsis Seeds, Jinshan Ke, Robert H. Behal, Stephanie L. Back, Basil J. Nikolau, Eve S. Wurtele, David J. Oliver

Eve Wurtele

Acetyl-coenzyme A (acetyl-CoA) formed within the plastid is the precursor for the biosynthesis of fatty acids and, through them, a range of important biomolecules. The source of acetyl-CoA in the plastid is not known, but two enzymes are thought to be involved: acetyl-CoA synthetase and plastidic pyruvate dehydrogenase. To determine the importance of these two enzymes in synthesizing acetyl-CoA during lipid accumulation in developing Arabidopsis seeds, we isolated cDNA clones for acetyl-CoA synthetase and for the ptE1α- and ptE1β-subunits of plastidic pyruvate dehydrogenase. To our knowledge, this is the first reported acetyl-CoA synthetase sequence from a plant source. The Arabidopsis ...


Chloride And Proton Binding In The E. Coli 2cl¯:1h+ Clc Exchanger, Catherine Chenal 2017 The Graduate Center, City University of New York

Chloride And Proton Binding In The E. Coli 2cl¯:1h+ Clc Exchanger, Catherine Chenal

All Graduate Works by Year: Dissertations, Theses, and Capstone Projects

The CLC family of membrane proteins is a ubiquitously expressed class of proton and usually voltage-activated chloride transporters involved in a myriad of physiological functions. Crystallographic structures identify up to three chloride binding sites: external, central and intracellular located in the inner half of the trans-membrane domain. The CLC proteins, except for the kidney isoforms, are gated by the extracellular side-facing gating Glutamate (Ex, E148 in CLC-ec1, the E. coli exchanger), which is thought to undergo a conformational change upon protonation.

To sort out how the thermodynamic paths to H+ coupled Cl¯ binding and conformational change in CLC-ec1 at the ...


Extracting Biochemical Parameters From Protein Distributions Of Vascular Cells, Partha Srinivasan 2017 Cleveland State University

Extracting Biochemical Parameters From Protein Distributions Of Vascular Cells, Partha Srinivasan

Partha Srinivasan

No abstract provided.


Mri-Based Susceptibility Mapping For In-Vivo Iron And Blood Oximetry Measurements, Hannah Erdevig 2017 University of Colorado, Boulder

Mri-Based Susceptibility Mapping For In-Vivo Iron And Blood Oximetry Measurements, Hannah Erdevig

Undergraduate Honors Theses

MRI is increasingly used in mapping tissue susceptibility to identify cerebral microbleeds associated with traumatic brain injury and pathological iron deposits associated with neurodegenerative diseases such as Parkinson's and Alzheimer's disease [1,2]. Accurate measurement is important for determining oxygen and iron content in blood vessels and tissue in the brain, which are in turn used for noninvasive clinical diagnosis and treatment assessments. Magnetic field distortions with a resolution of a few parts per billion can be measured using MRI phase maps. The field distortion map can then be inverted to obtain a quantitative susceptibility map. The primary ...


Code For "Noise-Enhanced Coding In Phasic Neuron Spike Trains", Cheng Ly, Brent D. Doiron 2017 Virginia Commonwealth University

Code For "Noise-Enhanced Coding In Phasic Neuron Spike Trains", Cheng Ly, Brent D. Doiron

Statistical Sciences and Operations Research Data

This zip file contains Matlab scripts and ode (XPP) files to calculate the statistics of the models in "Noise-Enhanced Coding in Phasic Neuron Spike Trains". This article is published in PLoS ONE.


Evolution Of The Kinetics And Dynamics Of Heme-Crevice Loop Regulating Chemistry In Human Cytochrome C, Shiloh M. Nold 2017 University of Montana, Missoula

Evolution Of The Kinetics And Dynamics Of Heme-Crevice Loop Regulating Chemistry In Human Cytochrome C, Shiloh M. Nold

Graduate Student Theses, Dissertations, & Professional Papers

Cytochrome c, cytc, is a metalloprotein that plays primary roles in electron transport and intrinsic apoptotic pathways. Much of the chemistry that cytc is involved with is regulated by a highly conserved region known as the heme crevice loop, consisting of residues 70-85. Only three of these residues (those at positions 81, 83 and 85) are not universally conserved within the evolutionary timeline. Here I look to elucidate possible evolutionary roles for several of the key residues known to be important in regulating heme chemistry of cytc.

I first address the role that lysine 72 plays in ...


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