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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 ...


Confirmation That Mrub_1751 Is Homologous To E. Coli Xylf, Mrub_1752 Is Homologous To E. Coli Xylh, And Mrub_1753 Is Homologous To E. Coli Xylg, Ben Price, Dr. Lori Scott 2018 Augustana College, Rock Island Illinois

Confirmation That Mrub_1751 Is Homologous To E. Coli Xylf, Mrub_1752 Is Homologous To E. Coli Xylh, And Mrub_1753 Is Homologous To E. Coli Xylg, Ben Price, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

In this project we investigated the biological function of the genes Mrub_1751, Mrub_1752 and Mrub_1753 (KEGG map number 02010). We predict these genes encode components of a D-xylose ATP Binding Cassette (ABC) transporter: 1) Mrub_1752 (DNA coordinates 1809004-1810224 on the forward strand) encodes the permease component (aka transmembrane domain), predicted to be an ortholog and 2) Mrub_1753 (DNA coordinates 1810227-1811000 on the forward strand) encodes the ATP-binding domain (aka nucleotide binding domain); and 3) Mrub_1751 (DNA coordinates 1807855-1808892 on the forward strand) encodes the solute binding protein. The ABC-transporter for M. ruber to transport D-xylose is homologous with the transporter ...


Evaluation Of Extracellular Matrix Composition And Rheology As Determinants Of Growth, Invasion, And Response To Photodynamic Therapy In 3d Cell Culture Models Of Pancreatic Ductal Adenocarcinoma, Gwendolyn M. Cramer 2017 University of Massachusetts Boston

Evaluation Of Extracellular Matrix Composition And Rheology As Determinants Of Growth, Invasion, And Response To Photodynamic Therapy In 3d Cell Culture Models Of Pancreatic Ductal Adenocarcinoma, Gwendolyn M. Cramer

Graduate Doctoral Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is a notoriously lethal disease characterized by prominent stromal involvement, which plays complex roles in regulating tumor growth and therapeutic response. The extracellular matrix (ECM)-rich stroma has been implicated as a barrier to drug penetration, although stromal depletion strategies have had mixed clinical success. It remains less clear how biophysical interactions with the ECM regulate invasive progression and susceptibilities to specific therapies. Here, an integrative approach combining 3D cell culture and quantitative imaging techniques is used to evaluate invasive behavior and motility as determinants of response to classical chemotherapy and photodynamic therapy (PDT), in which ...


Developing Algorithms For Quantifying The Super Resolution Microscopic Data: Applications To The Quantification Of Protein-Reorganization In Bacteria Responding To Treatment By Silver Ions, Sai Divya Challapalli 2017 University of Arkansas, Fayetteville

Developing Algorithms For Quantifying The Super Resolution Microscopic Data: Applications To The Quantification Of Protein-Reorganization In Bacteria Responding To Treatment By Silver Ions, Sai Divya Challapalli

Theses and Dissertations

Histone-like nucleoid structuring proteins (HNS) play significant roles in shaping the chromosomal DNA, regulation of transcriptional networks in microbes, as well as bacterial responses to environmental changes such as temperature fluctuations. In this work, the intracellular organization of HNS proteins in E. coli bacteria was investigated utilizing super-resolution fluorescence microscopy, which surpasses conventional microscopy by 10–20 fold in spatial resolution. More importantly, the changes of the spatial distribution of HNS proteins in E. coli, by addition of silver ions into the growth medium were explored. To quantify the spatial distribution of HNS in bacteria and its changes, an automatic ...


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 Complex Role Of Sequence And Structure In The Stability And Function Of The Tim Barrel Proteins, Yvonne H. Chan 2017 University of Massachusetts Medical School

The Complex Role Of Sequence And Structure In The Stability And Function Of The Tim Barrel Proteins, Yvonne H. Chan

GSBS Dissertations and Theses

Sequence divergence of orthologous proteins enables adaptation to a plethora of environmental stresses and promotes evolution of novel functions. As one of the most common motifs in biology capable of diverse enzymatic functions, the TIM barrel represents an ideal model system for mapping the phenotypic manifestations of protein sequence. Limits on evolution imposed by constraints on sequence and structure were investigated using a model TIM barrel protein, indole-3-glycerol phosphate synthase (IGPS). Exploration of fitness landscapes of phylogenetically distant orthologs provides a strategy for elucidating the complex interrelationship in the context of a protein fold.

Fitness effects of point mutations in ...


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 ...


Thermally-Assisted Acoustofluidic Separation For Bioanalytical Applications, Ata Dolatmoradi 2017 Florida International University

Thermally-Assisted Acoustofluidic Separation For Bioanalytical Applications, Ata Dolatmoradi

FIU Electronic Theses and Dissertations

Changes in the biomechanical properties of cells accompanying the development of various pathological conditions have been increasingly reported as biomarkers for various diseases and as a predictor of disease progression stages. For instance, cancer cells have been found to be less stiff compared to their healthy counterparts due to the proteomic and lipidomic dysregulations conferred by the underlying pathology. The separation and selective recovery of cells or extracellular vesicles secreted from such cells that have undergone these changes have been suggested to be of diagnostic and prognostic value.

This dissertation first describes the implementation of a stiffness-based separation of phosphatidylcholine-based ...


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 ...


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 ...


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 ...


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 ...


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