Biophysics Commons^™

Structural Studies On The Rubella Virus Capsid Protein And Its Organization In The Virion, Vidya Mangala Prasad

Open Access Dissertations

Rubella virus is a leading cause of birth defects due to infectious agents. When contracted during pregnancy, rubella infection leads to severe damage in fetuses. Despite its medical importance, very little is known about the structure of the pleomorphic rubella virus as compared to its alphavirus relatives. The rubella capsid protein is a critical structural component of virions as well as a key factor in virus-host interactions. Three crystal structures of the structural domain of the rubella capsid protein have been described here. The polypeptide fold of the capsid protomer has not been observed previously. The capsid protein structure, along …

Effects Of Dna Methylation Pattern On The Chromatin Structure, Isabel Cristina Jimenez Useche

Open Access Dissertations

DNA methylation plays an essential role in various biological processes such as stem cell differentiation, imprinting, X-chromosome inactivation, etc. Increased DNA methylation levels have been associated with chromatin compaction leading to gene silencing. For example, abnormal DNA methylation is associated with silencing of tumor suppressor genes and is observed in the onset of tumorigenesis. There is evidence suggesting that not all methylation events are relevant in chromatin compaction and the initiation of cancer. It seems that methylation at certain locations of the DNA might be key to start chromatin compaction and gene silencing, but the location of this methylation sites …

Structural And Functional Characterization Of The Endosome-Associated Deubiquitinating Enzyme Amsh, Christopher Williamson Davies

Open Access Dissertations

The endosomal sorting complexes required for transport (ESCRT) machinery is a ubiquitin-dependent molecular mechanism made of up of four individual complexes: ESCRT-0, -I, -II, III, that is necessary for regulating the degradation of cell surface receptors directed towards the lysosome. Not only are the ESCRTs implicated in endosomal sorting and trafficking of proteins, its members also have roles in other important biological processes such as: cytokinesis, HIV budding, transcriptional regulation, and autophagy. As a function of its involvement in several processes throughout the cell, the ESCRT machinery is implicated in a wide variety of diseases including cancer, neurological disease, bacterial …

Measuring And Modeling The Response Characteristics Of The Environmental Phosphate Transducer In Escherichia Coli, Chetan Sood

Open Access Dissertations

The PhoR/PhoB two-component system in Escherichia coli is a biological transducer that senses the limitation of environmental inorganic orthophosphate, the bacteria's preferred source of the essential nutrient phosphate, and transmits that information to the interior of the cell initiating a response that mitigates phosphate starvation. In the first part of this study, we present and apply a fluorescence microscopy technique to measure, in vivo, the dynamic response characteristics of the transducer with single-cell resolution. We report that the transience in the PhoR/PhoB TCS response is consistent with the transducer having a threshold sensitivity to the concentration of environmental phosphate, …

Computational Optogenetics: Empirically-Derived Voltage- And Light-Sensitive Channelrhodopsin-2 Model, John C. Williams, Jianjin Xu, Zhongju Lu, Aleksandra Klimas, Xuxin Chen, Christina M. Ambrosi, Ira S. Cohen, Emilia Entcheva

Department of Biomedical Engineering Faculty Publications

Channelrhodospin-2 (ChR2), a light-sensitive ion channel, and its variants have emerged as new excitatory optogenetic tools not only in neuroscience, but also in other areas, including cardiac electrophysiology. An accurate quantitative model of ChR2 is necessary for in silicoprediction of the response to optical stimulation in realistic tissue/organ settings. Such a model can guide the rational design of new ion channel functionality tailored to different cell types/tissues. Focusing on one of the most widely used ChR2 mutants (H134R) with enhanced current, we collected a comprehensive experimental data set of the response of this ion channel to different irradiances and voltages, …

Transformations In Matter And Energy: Student Learning And Inquiry To Inform Teaching, Jenny Dauer

Discipline-Based Education Research Group Speaker Series

Learning progressions are descriptions of increasing levels of sophistication of student reasoning about a topic based on empirical evidence. Our learning progression framework about student explanations of carbon-transforming processes (e.g. photosynthesis, cellular respiration) describes how student’s interconnected and mutually supporting ideas and practices are deeply embedded in discourse at all levels of achievement. My research is in two areas: 1) applying the learning progression framework for student explanations of carbon-transforming processes to describe the most productive pathways for student learning, 2) extending the research to student reasoning during inquiry activities about carbon-transforming processes. One finding is that students who consistently …

A Force Of Nature: Molecular Mechanisms Of Mechanoperception In Plants, Gabriele B. Monshausen, Elizabeth S. Haswell

Biology Faculty Research

The ability to sense and respond to a wide variety of mechanical stimuli-gravity, touch, osmotic pressure, or the resistance of the cell wall-is a critical feature of every plant cell, whether or not it is specialized for mechanotransduction. Mechanoperceptive events are an essential part of plant life, required for normal growth and development at the cell, tissue, and whole-plant level and for the proper response to an array of biotic and abiotic stresses. One current challenge for plant mechanobiologists is to link these physiological responses to specific mechanoreceptors and signal transduction pathways. Here, we describe recent progress in the identification …

Efficacy Of Gold Silica Nanoshells And Gold Nanorods For Photothermal Therapy Of Human Glioma Spheroids, Suyog Jung Chhetri

UNLV Theses, Dissertations, Professional Papers, and Capstones

Gold-based nanoparticles including gold-silica nano-spheres and gold nano-rods have been investigated for a number of therapeutic and diagnostic applications. The ability of these nanoparticles to convert light into heat energy makes them particularly appealing for photothermal therapy in which cancer cells are destroyed via light-induced heat generation. The overall objective of the study is to compare the efficacy of gold-silica nano-spheres and gold nano-rods in an in vitro system consisting of human brain tumor (glioma) spheroids.

Delivery of the nanoparticles to the spheroids was accomplished using murine macrophages. Nanoparticles (spheres or rods) were incubated with macrophages for 24 hours. Thereafter, …

Raman Spectroscopic Analysis Of Human Skin Tissue Sections Ex-Vivo: Evaluation Of The Effects Of Tissue Processing And Dewaxing, Syed Mehmood Ali, Franck Bonnier, Ali Tfayli, Helen Lambkin, Kathleen Flynn, Vincent Mcdonagh, Claragh Healy, Thomas Lee, Fiona Lyng, Hugh Byrne

Articles

Raman spectroscopy coupled with K-means clustering analysis (KMCA) is employed to elucidate the biochemical structure of human skin tissue sections, and the effects of tissue processing. Both hand and thigh sections of human cadavers were analysed in their unprocessed and formalin fixed paraffin processed (FFPP) and subsequently dewaxed forms. In unprocessed sections, KMCA reveals clear differentiation of the stratum corneum, intermediate underlying epithelium and dermal layers for sections from both anatomical sites. The stratum corneum is seen to be relatively rich in lipidic content; the spectrum of the subjacent layers is strongly influenced by the presence of melanin, while that …

From Gibbons To Gymnasts: A Look At The Biomechanics And Neurophysiology Of Brachiation In Gibbons And Its Human Rediscovery, Emma Et Pennock

Student Works

This conference paper serves to examine the evolutionary linkages of a brachiating ancestor in humans, the biomechanical and neurophysiology of modern day brachiators, and the human rediscovery of this form of locomotion. Brachiation is arguably one of the most metabolically effective modes of travel by any organism and can be observed most meritoriously in Gibbons. The purpose of the research conducted for this paper was to encourage further exploration of the neurophysiological similarities and differences between humans and non-human primates. The hope is that in spurring more interest and research in this area, further possibilities for rehabilitating brain injury will …

Biophysical Studies Of Styrene-Maleic Acid Copolymer Stabilized Membrane Mimetics, Diane Yu

University Scholar Projects

Traditional methods of isolating membrane proteins involve the use of detergents that destabilize the membrane environment. Biophysical studies of membrane proteins are challenged by the requirement of a stable membrane platform. Lipodisq® nanoparticles are novel membrane mimetics that consist of 3:1 styrene-maleic acid copolymer encircling phospholipids to form discoidal species on the order of 10 nm in diameter. Bacteriorhodopsin was previously incorporated into Lipodisq® nano-particles from its native purple membrane without the addition of detergent. In this study, dynamic light scattering was used to investigate the stability of empty Lipodisq® nano-particles over time. These data show that Lipodisq® nano-particles are …

Interactions Between Ions And Lysenin Nanochannels And Their Potential Applications As Biosensors, Radwan Awwad Al Faouri

Graduate Theses and Dissertations

Lysenin is classified as a pore-forming toxin protein that is isolated from the earthworm Eisenia fetida and consists of 297 amino acids [1]. Lysenin inserts large conducting pores (3.0-4.7 nm in diameter) into artificial membranes (BLM) which include sphingomyelin. These pores (channels) are open and oriented upon insertion into the bilayer lipid membrane. Lysenin channels gate at positive voltages (voltage-induced gating), but not at negative voltages. Lysenin pores also exhibit activity modulation in response to changes in ionic strength and pH, indicating that electrostatic interaction is responsible for Lysenin conductance activities. In this line of inquiries, and by modulating Lysenin …

Dynamics And Model Of The Pore-Forming Protein Lysenin, Eric Krueger

Graduate Theses and Dissertations

Membrane transporters are a class of membrane proteins that function to provide a pathway across a cell membrane for the movement of ions and biomolecules. Investigations into the regulatory mechanism of these systems are hindered by their extensive preparation requirements compounded by their fragility and instability. However, lysenin, a pore-forming protein extracted from the earthworm Eisenia foetida, provided a unique opportunity to study a protein which is stable in both a soluble and membrane phase. Lysenin channels possess several important properties characteristic of ion channels without the inherent difficulties that plague investigations with biologically vital membrane transporters like voltage-gated ion …

The Geometry And Sensitivity Of Ion-Beam Sculpted Nanopores For Single Molecule Dna Analysis, Ryan Connor Rollings

Graduate Theses and Dissertations

In this dissertation, the relationship between the geometry of ion-beam sculpted solid-state nanopores and their ability to analyze single DNA molecules using resistive pulse sensing is investigated. To accomplish this, the three dimensional shape of the nanopore is determined using energy filtered and tomographic transmission electron microscopy. It is shown that this information enables the prediction of the ionic current passing through a voltage biased nanopore and improves the prediction of the magnitude of current drop signals when the nanopore interacts with single DNA molecules. The dimensional stability of nanopores in solution is monitored using this information and is improved …

Erratum: Characterizing The Biomolecular Interactions Between Insulin And G-Quadruplexdna (Biophysical Journal (2013) 104:2 (419a)), Nicole L. Michmerhuizen, Christine M. Timmer, Margaret Van Winkle, Kylin Hamann

University Faculty Publications and Creative Works

No abstract provided.

Erratum: Characterizing The Biomolecular Interactions Between Insulin And G-Quadruplexdna (Biophysical Journal (2013) 104:2 (419a)), Nicole L. Michmerhuizen, Christine M. Timmer, Margaret Van Winkle, Kylin Hamann

University Faculty Publications and Creative Works

No abstract provided.

Rescuing Acetylcholinesterase From Nerve Agent Inhibition: Protein Dynamics Driven Drug Discovery, Aiyana M. Emigh, Brian Bennion

STAR Program Research Presentations

Severe morbidity and mortality consequences result from irreversible inhibition of human acetylcholinesterase by organophosphates (OPs). Oxime-based reactivators are currently the only available treatments but lack efficacy in the central nervous system (CNS) where the most damage occurs. Computational docking and molecular dynamics (MD) simulations reveal complex structural barriers that may reduce oxime efficacy. These results may guide future drug designs of more effective countermeasures.

Biophysical Approaches To Human Genetic Disease: Adsl Deficiency As A Model, Stephen P. Ray

Electronic Theses and Dissertations

Biophysical tools are becoming more useful in approaching human genetic disease. The pathogenic mechanisms behind many disorders have been attributed to protein loss of function or gain in toxic function. For example, changes in the protein Adenylosuccinate Lyase (ADSL) lead to ADSL deficiency, a disorder that causes symptoms ranging from epilepsy to expression of autistic features. Biophysics offers different tools to study intrinsic properties of proteins. We have applied such tools to study the enzyme kinetics and protein stability of ADSL and two mutations (R426H and R303C) to formulate better hypotheses regarding the pathogenic mechanism. Enzyme kinetic findings indicate a) …

How Atomic Level Interactions Drive Membrane Fusion: Insights From Molecular Dynamics Simulations, Navendu Bhatnagar

Wayne State University Dissertations

This project is focused on identifying the role of key players in the membrane fusion process at the atomic level with the use of molecular dynamics simulations. Membrane fusion of apposed bilayers is one of the most fundamental and frequently occurring biological phenomena in living organisms. It is an essential step in several cellular processes such as neuronal exocytosis, sperm fusion with oocytes and intracellular fusion of organelles to name a few. Membrane fusion is a frequent process in a living organism but is still not fully understood at the atomic level in terms of the role of various factors …

Primary Pathways Of Intracellular Ca2+ Mobilization By Nanosecond Pulsed Electric Field, Iurii Semenov, Shu Xiao, Andrei G. Pakhomov

Bioelectrics Publications

Permeabilization of cell membranous structures by nanosecond pulsed electric field (nsPEF) triggers transient rise of cytosolic Ca²⁺ concentration ([Ca²⁺]_i), which determines multifarious downstream effects. By using fast ratiometric Ca²⁺ imaging with Fura-2, we quantified the external Ca²⁺ uptake, compared it with Ca²⁺ release from the endoplasmic reticulum (ER), and analyzed the interplay of these processes. We utilized CHO cells which lack voltage-gated Ca²⁺ channels, so that the nsPEF-induced [Ca²⁺]_i changes could be attributed primarily to electroporation. We found that a single 60-ns pulse caused fast [Ca2+]_i increase …