Biophysics Commons^™

Development Of Computational To Ols To Target Microrna, Luo Song

Dissertations and Theses (Open Access)

MicroRNAs (a.k.a, miRNAs) play an important role in disease development. However, few of their structures have been determined and structure-based computational methods remain challenging in accurately predicting their interactions with small molecules. To address this issue, my thesis is to develop integrated approaches to screening for novel inhibitors by targeting specific structure motifs in miRNAs. The project starts with implementing a tool to find potential miRNA targets with desired motifs. I combined both sequence information of miRNAs and known RNA structure data from Protein Data Bank (PDB) to predict the miRNA structure and identify the motif to target, then I …

Ionic Mechanism Of Lysosomal Function And Cell Metabolism, Jian Xiong

Dissertations and Theses (Open Access)

Two Pore Channels (TPCs) are endolysosomal ion channels that are permeable to sodium and calcium. Defects in TPCs have been implicated to impair vesicle trafficking, autophagy and cell metabolism control; however, the detailed mechanism remains largely unknown. In this study, I show that TPCs are critical for appropriate cargo delivery to the lysosomes and deletion of either TPC1 or TPC2 leads to delayed clearance of autophagosomes, resulting in enlarged lysosomes and accumulated contents inside the lysosomes. Cells with both TPC deleted also exhibit 50% reduction in lysosomal amino acids under normal culture conditions, leading to reduced homeostatic mTORC1 activation.

Glutamine …

Interactions Of The Nlrp3 Inflammasome Complex, Nyasha Makoni

Dissertations

The innate immune system is the first line of defense in response to invasion by pathogens. One of the major pathways in the innate immune system involves a three-protein complex known as the NLRP3 inflammasome. This complex comprises of NLRP3, ASC, and procaspase-1. In response to stimuli, the inflammasome assembles to activate caspase-1 which subsequently facilitates production of interleukin-1β (IL-1β), an inflammatory cytokine. The NLRP3 inflammasome has been implicated in a variety of inflammatory disorders including Alzheimer’s disease (AD). Amyloid beta (Aβ) is the protein that causes AD and Aβ deposits in the brain activate microglia resulting in chronic inflammation. …

Data-Driven Modeling Of The Causes And Effects Of Interneuronal Dysfunction In Alzheimer’S Disease And Dravet Syndrome, Carlos Perez

USF Tampa Graduate Theses and Dissertations

One of the defining features of Alzheimer’s disease (AD) is the increased cleavage of the amyloid precursor protein (APP), causing abnormally high levels of the aggregation form of amyloid beta (Aβ ). Many studies have shown that both AD patients and AD mice models exhibit abnormal network activity, including hypersynchronous excitatory neuron behavior, altered brain rhythms, and in some instances epileptic seizures when exposed to high levels of Aβ In particular, strong experimental evidence suggests that it is the small globular amyloid oligomers (gOs) and curvilinear fibrils (CFs) rather than the more stable, late stage rigid fibrils (RFs) that cause …

Mathematical Modelling Of Temperature Effects On The Afd Neuron Of Caenorhabditis Elegans, Zachary Mobille, Rosangela Follmann, Epaminondas Rosa

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Origins Of Amyloid Oligomers And Novel Approaches For Their Detection, Jeremy Barton

USF Tampa Graduate Theses and Dissertations

Alzheimer’s disease, type II diabetes, and other amyloid diseases are known to be associated with the formation of amyloid aggregates. It has been thoroughly researched whether amyloid fibrils or oligomers are the main culprit for these diseases, and recent evidence has connected oligomers as the most disease relevant aggregate species. However, many difficulties have arose in confirming this hypothesis. Techniques for oligomer detection are often limited in their sensitivity, and in many cases are unable to distinguish oligomers from rigid fibrils. Additionally, the role oligomer splay in fibril assembly is still unclear, and has led to the belief that different …

Biomechanical And Biophysical Properties Of Breast Cancer Cells Under Varying Glycemic Regimens, Diganta Dutta, Xavier-Lewis Palmer, Jose Ortega-Rodas, Vasundhara Balraj, Indrani Ghosh Dastider, Surabhi Chandra

Electrical & Computer Engineering Faculty Publications

Diabetes accelerates cancer cell proliferation and metastasis, particularly for cancers of the pancreas, liver, breast, colon, and skin. While pathways linking the 2 disease conditions have been explored extensively, there is a lack of information on whether there could be cytoarchitectural changes induced by glucose which predispose cancer cells to aggressive phenotypes. It was thus hypothesized that exposure to diabetes/high glucose alters the biomechanical and biophysical properties of cancer cells more than the normal cells, which aids in advancing the cancer. For this study, atomic force microscopy indentation was used through microscale probing of multiple human breast cancer cells (MCF-7, …

Axonal Blockage With Microscopic Magnetic Stimulation, Hui Ye

Biology: Faculty Publications and Other Works

Numerous neurological dysfunctions are characterized by undesirable nerve activity. By providing reversible nerve blockage, electric stimulation with an implanted electrode holds promise in the treatment of these conditions. However, there are several limitations to its application, including poor bio-compatibility and decreased efficacy during chronic implantation. A magnetic coil of miniature size can mitigate some of these problems, by coating it with biocompatible material for chronic implantation. However, it is unknown if miniature coils could be effective in axonal blockage and, if so, what the underlying mechanisms are. Here we demonstrate that a submillimeter magnetic coil can reversibly block action potentials …

The Impacts Of Membrane Modulators On Membrane Material Properties At Microscopic And Nanoscopic Levels, Chinta Mani Aryal

USF Tampa Graduate Theses and Dissertations

Peptide-membrane interactions depict the cell’s response to an external molecule. This is a critical event to evaluate the peptide’s function and effect as well as the response of target molecule. The understanding of the mechanism of action of peptide in a molecular level is important, for example, this may be useful in developing the therapeutic strategy. Peptides are the functional macromolecules which are actively researched among bio-related fields. Model membrane systems that mimic the real cell have been useful platform to test the perturbation upon peptide addition. In this thesis, we investigate the membrane modulation behavior of three peptides (modulators) …

Single‐Molecule 3d Orientation Imaging Reveals Nanoscale Compositional Heterogeneity In Lipid Membranes, Jin Lu, Hesam Mazidi, Tianben Ding, Oumeng Zhang, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

In soft matter, thermal energy causes molecules to continuously translate and rotate, even in crowded environments, thereby impacting the spatial organization and function of most molecular assemblies, such as lipid membranes. Directly measuring the orientation and spatial organization of large collections (>3000 molecules μm⁻²) of single molecules with nanoscale resolution remains elusive. In this paper, we utilize SMOLM, single‐molecule orientation localization microscopy, to directly measure the orientation spectra (3D orientation plus “wobble”) of lipophilic probes transiently bound to lipid membranes, revealing that Nile red's (NR) orientation spectra are extremely sensitive to membrane chemical composition. SMOLM images resolve …

Retrieving Functional Pathways Of Biomolecules From Single-Particle Snapshots, Ali Dashti, Ghoncheh Mashayekhi, Mrinal Shekhar, Danya Ben Hail, Salah Salah, Peter Schwander, Amedee Des Georges, Abhishek Singharoy, Joachim Frank, Abbas Ourmazd

Publications and Research

A primary reason for the intense interest in structural biology is the fact that knowledge of structure can elucidate macromolecular functions in living organisms. Sustained effort has resulted in an impressive arsenal of tools for determining the static structures. But under physiological conditions, macromolecules undergo continuous conformational changes, a subset of which are functionally important. Techniques for capturing the continuous conformational changes underlying function are essential for further progress. Here, we present chemically-detailed conformational movies of biological function, extracted data-analytically from experimental single-particle cryo-electron microscopy (cryo-EM) snapshots of ryanodine receptor type 1 (RyR1), a calcium-activated calcium channel engaged in the …

Convex Relaxations For Particle-Gradient Flow With Applications In Super-Resolution Single-Molecule Localization Microscopy, Hesam Mazidisharfabadi

McKelvey School of Engineering Graduate Student Theses & Dissertations

Single-molecule localization microscopy (SMLM) techniques have become advanced bioanalytical tools by quantifying the positions and orientations of molecules in space and time at the nanoscale. With the noisy and heterogeneous nature of SMLM datasets in mind, we discuss leveraging particle-gradient flow 1) for quantifying the accuracy of localization algorithms with and without ground truth and 2) as a basis for novel, model-driven localization algorithms with empirically robust performance. Using experimental data, we demonstrate that overlapping images of molecules, a typical consequence of densely packed biological structures, cause biases in position estimates and reconstruction artifacts. To minimize such biases, we develop …

Snow-Albedo Feedback In Northern Alaska: How Vegetation Influences Snowmelt, Lucas C. Reckhaus

Theses and Dissertations

This paper investigates how the snow-albedo feedback mechanism of the arctic is changing in response to rising climate temperatures. Specifically, the interplay of vegetation and snowmelt, and how these two variables can be correlated. This has the potential to refine climate modelling of the spring transition season. Research was conducted at the ecoregion scale in northern Alaska from 2000 to 2020. Each ecoregion is defined by distinct topographic and ecological conditions, allowing for meaningful contrast between the patterns of spring albedo transition across surface conditions and vegetation types. The five most northerly ecoregions of Alaska are chosen as they encompass …

Urban Air Quality Modeling: Evaluating Impacts Of Ecoroofs On Urban Air Quality In Portland, Oregon, Danlyn L. Brennan, Selina Teng

altREU Projects

In this work, the authors present a mathematical model simulating the impact of ecoroof vegetation on air quality in an urban microclimate. An ecoroof is a layer of vegetation established on rooftops to reduce stormwater runoff, mitigate heat, and enhance air quality. Certain plant species in ecoroofs may however have a detrimental effect on air quality, due to their emission of biogenic volatile organic compounds (BVOCs), which include potentially reactive species such as isoprene. These chemical species can interact with urban air pollution, particularly NOx produced by car traffic, to create other harmful pollutants such as ozone and particulate matter …

Methods To Investigate Hyperthermia Induced By Tumor Treating Fields, Ruchi Singh

Dissertations and Theses (Open Access)

Tumor Treating Fields (TTFields) are an antineoplastic treatment delivered via application of alternating electric fields using insulated transducer arrays placed directly on the skin in the region surrounding the tumor. TTF’s is a non-invasive application of low-intensity (1-3 V/cm), intermediate-frequency (100-500 kHz) alternating electric fields. The predominant mechanism by which TTFields are thought to kill tumor cells is the disruption of mitosis through the depolymerization of microtubules and interruption of the spindle structure leading to mitotic catastrophe and the formation of non-viable daughter cells. Tumor Treating fields do not stimulate nerves and muscle because of their high frequency, and do …

Validation Of Nanosecond Pulse Cancellation Using A Quadrupole Exposure System, Hollie A. Ryan

Biomedical Engineering Theses & Dissertations

Nanosecond pulsed electric fields (nsPEFs) offer a plethora of opportunities for developing integrative technologies as complements or alternatives to traditional medicine. Studies on the biological effects of nsPEFs in vitro and in vivo have revealed unique characteristics that suggest the potential for minimized risk of complications in patients, such as the ability of unipolar nsEPs to create permanent or transient pores in cell membranes that trigger localized lethal or non-lethal outcomes without consequential heating. A more recent finding was that such responses could be diminished by applying a bipolar pulse instead, a phenomenon dubbed bipolar cancellation, paving the way …

No Oxygen, No Water: The Unique Physiology Of Annual Killifish Embryos Across Development, Daniel Erik Zajic

Dissertations and Theses

For most vertebrates, an abundance of oxygen is necessary for the production of ATP and the maintenance of cellular homeostasis. The absence of oxygen, even for brief periods, quickly leads to ATP depletion which can lead to irreparable damages to sensitive organs, such as the brain and heart. However, certain vertebrates demonstrate an extraordinary ability to thrive and recover fully from periods of no oxygen (anoxia). The annual killifish (Austrofundulus limnaeus) lives in ephemeral ponds in the Maracaibo basin of Venezuela and their embryos have the remarkable ability to not only survive anoxic periods for months, but also …

Phenotypic Switching Of Bacterial Cells In Extreme Environments, Sudip Nepal

Graduate Theses and Dissertations

A large number of terrestrial microbial lives thrive in extremes of environmental conditions, including extremes of pressure, temperature, salinity, pH, and a combination of them. For example, all the marine biomass thrive at high hydrostatic pressure depending on depth. The temperature in the ocean can be very high near the hydrothermal vents and salinity and pH depends on the composition of salt in the surrounding areas. On the surface, hot springs, lakes and geysers provide high temperature conditions, while many places are permafrost regions with subzero temperatures. There is an emerging body of work on the viability, genomics, and metagenomics …

Circuits With Broken Fibration Symmetries Perform Core Logic Computations In Biological Networks, Ian Leifer, Flaviano Morone, Saulo D. S. Reis, José S. Andrade Jr., Mariano Sigman, Hernán A. Makse

Publications and Research

We show that logic computational circuits in gene regulatory networks arise from a fibration symmetry breaking in the network structure. From this idea we implement a constructive procedure that reveals a hierarchy of genetic circuits, ubiquitous across species, that are surprising analogues to the emblematic circuits of solid-state electronics: starting from the transistor and progressing to ring oscillators, current-mirror circuits to toggle switches and flip-flops. These canonical variants serve fundamental operations of synchronization and clocks (in their symmetric states) and memory storage (in their broken symmetry states). These conclusions introduce a theoretically principled strategy to search for computational building blocks …

The Kinetic Signatures Of Antibody Binding To M. Genitalium Adhesin Protein Fragments, Margaret C. Lunn

Honors Projects

Mycoplasma genitalium is a sexually-transmitted bacterial pathogen that persists in patients by adherence to cells through matrix glycoproteins and evasion of host antibodies. The MgpB and MgpC adherence proteins consist of variable and conserved regions. Variable regions undergo antigenic variation to avoid specific antibodies. However, the C-terminus (MgpB-4a) does not vary, is highly immunogenic, and antibodies to this region inhibit attachment and promote bacterial killing in vitro. To better understand how M. genitalium avoids clearance by antibodies to MgpB-4a in vivo we used surface plasmon resonance (SPR) to measure kinetic values of binding events. Binding of polyclonal rabbit antibodies (3935 …