Life Sciences Commons^™

Interactions Of Amyloid Peptides With Lipid Membranes, Yanxing Yang

Dissertations

The aggregation of amyloid proteins into fibrils is a hallmark of several diseases including Alzheimer’s (AD), Parkinson’s, and Type II diabetes. This aggregation process involves the formation of small size oligomers preceding the formation of insoluble fibrils. Recent studies have shown that these oligomers are more likely to be responsible for cell toxicity than fibrils. A possible mechanism of toxicity involves the interaction of oligomers with the cell membrane compromising its integrity. In particular, oligomers may form pore-like structures in the cell membrane affecting its permeability or they may induce lipid loss via a detergent-like effect. This dissertation aims to …

Angiogenic Supports For Microvascular Engineering, Zain Siddiqui

Dissertations

Ischemic tissue disease is caused by a lack of circulation / blood supply to tissue. This can be treated by introducing a number of angiogenic (pro-blood vessel forming) factors into the tissue. This work presents strategies for ischemic tissue treatment utilizing a novel proangiogenic self-assembling peptide hydrogel platform. To demonstrate the utility of this platform, its use alone as an angiogenic therapeutic (both alone as a self-assembling hydrogel and with two-component systems), and its ability to vascularize implants is explored. Due to these angiogenic scaffolds demonstrating efficacy to regenerate microvasculature, this work evaluates diseases that can be treated by the …

Dissecting Interactions Across Gene Regulatory Layers In C. Elegans, Morgan Taylor

Biological Sciences Theses and Dissertations

The nematode Caenorhabditis elegans is a powerful tool for studying nervous system genetics. Though relatively simple compared to mammals, C. elegans boasts a remarkably well-conserved neuronal genome and proteome, and its utility in the characterization of neuronal genes has been well-established. However, gene expression is often controlled by complex interactions between multiple genes, and teasing apart the functions of individual genes within such networks remains a challenge. Dissecting these interaction networks is crucial in determining the multifaceted functions of important, conserved regulatory genes. Here we explore interactions between gene regulatory layers in the C. elegans nervous system, employing a synthetic …

Quantum Computations And Molecular Dynamics Simulations: From The Fundamentals Of Antimicrobial Resistance To Neurological Diseases, Angel Tamez

Electronic Theses and Dissertations

Biophysical phenomena are modeled using a combination of quantum and classical methods to interpret and supplement three distinct and diverse problems in this dissertation. In the first project, decarboxylation reactions are ubiquitous across chemical and biological disciplines, yet the origin of non-catalytic solvent effects remains elusive. Specific solvent structure and energetics have not been well described for the monoanion of malonate, nor corrected from the gas-phase charge-assisted intramolecular hydrogen bond model known as “pseudochair”. In the aqueous phase, a low-lying energy conformer known as the “orthogonal conformation” is computed to be preferred by a three-water cluster of hydrogen bonding over …

Metoprolol Disrupts Sterol Biosynthesis Through Inhibition Of 7-Dehydrocholesterol Reductase (Dhcr7), Luke B. Allen

Theses & Dissertations

Cholesterol is essential for life. It is particularly important in the brain as it relies on de novo synthesis of cholesterol following the formation of the blood brain barrier (BBB). As such, disrupting sterol biosynthesis during neurodevelopment can have devastating outcomes. The most common post-lanosterol sterol biosynthesis disorder, Smith-Lemli-Opitz Syndrome, arises from a faulty DHCR7 enzyme. DHCR7 has also been shown to be inhibited by several psychotropic medications. Here we assess six beta-blockers and their effects on sterol biosynthesis in vitro. Two beta-blockers, metoprolol and nebivolol strongly inhibit DHCR7 in four separate in vitro models of both mouse and …

Novel Mechanisms Of Protein Kinase C Α Regulation And Function, Xinyue Li

Theses & Dissertations

Protein kinase Cα (PKCα) is a member of the PKC family of serine/threonine kinases, which have been implicated in regulation of many cellular processes, including cell proliferation, differentiation, survival, and transformation. A large body of evidence from the Black laboratory and others support an anti-proliferative function of PKCα in normal epithelial tissues, including the intestinal mucosa and endometrial epithelium. PKCα is also tumor suppressive in epithelial cancers, such as colorectal cancer (CRC) and endometrial cancer (EC). However, a major obstacle to harnessing the tumor suppressive functions of PKCα to benefit patients is the widespread loss of PKCα expression in tumors. …

Dynamics Of Nucleosome Assembly Characterized By Atomic Force Microscopy, Tommy Stormberg

Theses & Dissertations

Nucleosomes are the basic repeating unit defining the assembly and function of chromatin. Understanding the fundamental mechanisms of nucleosome structure and dynamics is critical to elucidating the chromatin assembly process. This dissertation describes my work in elucidating the role of different factors that drive the nucleosome dynamics.

In my first study, we characterized, for the first time, the effect of sequence on nucleosome assembly. We then characterized the role of internucleosomal interactions, discovering a critical role internucleosomal interactions in the assembly of higher order structures.

Based on the previous study and literature regarding histone tails, we hypothesized the histone H4 …

The Role Of Parkin In Mitochondrial Dna, Eliezer Lichter

Theses & Dissertations

Mitochondria are at the center of biological phenomena such as aging and diseases, especially neurodegenerative diseases. While the discovery of mitochondria only came approximately 200 years after the cell was discovered, a lot of progress has been made since. The mitochondrial genome encodes proteins vital for mitochondrial function. These proteins are only a subset of the proteins present in mitochondria; the rest are nuclear encoded. The nucleus also encodes cytosolic proteins vital for mitochondrial maintenance. One of these is Parkin, an E3 ubiquitin ligase that ubiquitinates mitochondrial proteins as mitochondria become depolarized. Its activity has been shown to be involved …

Nanoparticle Conjugated Photosensitizer For Targeted Photodynamic Inactivation Of Cancer Cells, Symone D. Crowder

Honors College Theses

Photodynamic therapy (PDT) is considered to be a potential replacement for traditional methods of chemotherapy. It includes the administration of photosensitizing agents (PS), which generate reactive oxygen species (ROS) upon excitation at a specific wavelength. With new outlooks and techniques, cancer research is advancing each day. It has allowed the progress of several theranostic drug delivery systems (DDS) exploring the area of nanomedicine.2 In the present work, a Rhodamine derivative, Rhodamine 6G (R6G) was used as the PS. In general, rhodamine compounds undergo cytotoxic reactions on photoexcitation by electron transfer reactions with folic acid within cells, making them a favorable …

Insights Into The Non-Osmoregulatory Function Of A Pollen-Specific Mechanosensitive Ion Channel, Kari Miller

Arts & Sciences Electronic Theses and Dissertations

Pollen, the male gametophyte of flowering plants, delivers the sperm cells to the ovule to carry out sexual reproduction. During this process, the pollen grain undergoes dramatic physical changes. Survival requires careful control of cell mechanics, particularly the balance between protoplast expansion and cell wall resistance. One control mechanism is the use of a mechanosensitive (MS) ion channel, MscS-Like (MSL)8. This pollen-specific protein was previously shown to be essential for pollen survival during hydration and was proposed to function as a tension-gated osmoregulator. However, direct proof of osmoregulation during initial hydration has not yet been found. In fact, studies of …

A Structural Perspective On Neutralizing Antibodies To Flaviviruses And Coronaviruses, John Michael Errico

Arts & Sciences Electronic Theses and Dissertations

The presence of neutralizing antibodies typically correlates strongly with protection from infection, particularly for RNA viruses; elicitation of neutralizing antibody responses is thus the primary goal of most vaccines, and monoclonal antibodies (mAbs) can be leveraged as potent therapeutics. Thus, understanding the properties of individual antibodies that comprise polyclonal antibody responses and their epitopes is essential for countermeasure design. In this dissertation, I explore the epitopes and functional properties of monoclonal antibodies targeting the structural proteins of two families of RNA viruses, flaviviruses and coronaviruses.

Flaviviruses are globally distributed arthropod-borne positive-sense RNA viruses transmitted primarily by either mosquitos or ticks. …

Functional Analysis Of Recurrent Non-Coding Variants In Human Melanoma, Paula Maria Godoy

Arts & Sciences Electronic Theses and Dissertations

Worldwide incidence rates of cutaneous melanoma are increasing, and while survival rates for early stages of melanoma are high, rates drop precipitously for metastatic melanomas or those that are unable to be targeted by currently available treatments. As melanomas have a propensity to quickly metastasize, understanding the contributions of melanoma initiation remains critical for early intervention. Onset of melanoma is characterized most by mutations that stimulate mitogen-activated protein kinase (MAPK) signaling, disrupt DNA damage checkpoints, and trigger mechanisms to bypass senescence through elongation of telomeres. Additionally, in zebrafish melanoma models, the earliest cluster of melanoma-initiating cells activate expression of a …

A Universal Mechanism Of G Protein Inhibition, Tyson Daniel Todd

Arts & Sciences Electronic Theses and Dissertations

G protein coupled receptors transduce a truly staggering number of diverse extracellular signals including chemical messengers, physical force, and even photons into specific cellular responses through their coupling to heterotrimeric G proteins. G proteins amplify the originating signal through their binding to downstream effectors, activating a complex network of overlapping responses that allow the cell to respond perfectly to that specific stimulus. It is critical to the cell that this process is carried out faithfully in order to respond to the myriad environmental cues and avoid injury, exhaustion, and death for the individual cell or the development of pathology if …

Bis-Indolyl Compounds And The Induction Of Apoptosis In T98g Glioblastoma Multiforme Cells, Margot C. Brown

Seton Hall University Dissertations and Theses (ETDs)

1,1-bis(3’idolyl)-1(aryl)methane compounds (BIM compounds) have been shown to have anti-cancer properties in colon cancer, bladder cancer, and leukemia cells. The purpose of this work was to determine if BIM compounds could be an effective treatment of glioblastoma multiforme. Sulforhodamine B (SRB) assays showed that 20µM of the BIM compounds could inhibit cellular proliferation of the T98G glioblastoma multiforme cell line over 72 hours. Then immunoblotting was used to analyze the molecular pathway induced by BIM compounds. An increase in the expression of both BAX and cleaved caspase 3 suggest BIM compounds activate programmed cell death, or apoptosis in glioblastoma cells. …

Next-Generation Sequencing Shows Increasing Temperatures Affect Stream Fungal Communities, Regan Hodgson

Electronic Theses and Dissertations

Under climate change predictions, surface air temperature is expected to continue to rise and will likely affect functioning of stream ecosystems and microbial communities. Aquatic hyphomycetes are key fungal decomposers of plant litter in headwater streams controlling carbon, energy, and nutrient flows to higher trophic levels. This project addressed the effects of temperature on stream fungal communities in two recently conducted experiments (microcosm and streamside channel studies) using Illumina sequencing. The objectives were to determine (1) if temperature affects community structure of stream fungi based on relative abundances of ITS2 rDNA sequences, (2) if the effects of temperature on aquatic …

Dynamics Of Redox-Driven Molecular Processes In Local And Systemic Plant Immunity, Philip Berg

Theses and Dissertations

The work here presents two main parts. In the first part, chapters 1 – 3 focus on dynamical systems modeling in plant immunity, whereas chapters 4 – 6 describe contributions to computational modeling and analysis of proteomics and genomics data. Chapter 1 investigates dynamical and biochemical patterns of reversibly oxidized cysteines (RevOxCys) during effector-triggered immunity (ETI) in Arabidopsis, examines the regulatory patterns associated with Arabidopsis thimet oligopeptidase 1 and 2’s (TOP1 and TOP2), roles in the RevOxCys events during ETI, and analyzes the redox phenotype of the top1top2 mutant. The second chapter investigates the peptidome dynamics during ETI …

Molecular Basis Of Viroid Rna-Templated Transcription, Shachinthaka D. Dissanayaka Mudiyanselage

Theses and Dissertations

Transcription is a fundamental process catalyzed by DNA-dependent RNA polymerases (DdRPs). Interestingly, some DdRPs can use both DNA and RNA as templates for transcription. This RNA-dependent RNA polymerase (RdRP) activity of DdRPs is used by RNA-based pathogens such as viroids and hepatitis delta virus for replication. In addition, RdRP activity of DdRPs widely occurs in various organisms to regulate gene transcription. Despite the importance of this intrinsic RdRP activity of DdRPs, associated factors and mechanisms are in their infancy stage. We employed potato spindle tuber viroid (PSTVd) as a model to study RNA-templated transcription. Here, we present evidence showing that …

Investigating The Involvement Of The Tick Vector In The Induction Of Alpha-Galactose Hypersensitivity (Alpha-Gal Syndrome, Red Meat Allergy) In The United States., Gary Crispell

Dissertations

Alpha-gal syndrome (AGS or sometimes called red meat allergy) is a result of the development of specific IgE antibodies to the oligosaccharide galactose-α-1,3-galactose (α-gal) after a person has had exposure to tick bites. This dissertation investigates four common tick species found in North America: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) for the presence of α-gal by utilizing a combination of immunoproteomic approaches and carbohydrate analysis techniques.

Anti-α-gal IgM antibodies (M86) were used in immunoblotting to detect …

Screening Anti-Pd-L2 Peptides As Antitumor Ligands Using Phage Display, Chien Tran Phuoc

Honors Projects

Cancer still remains one of the top leading causes of death in America. Recently, programmed cell death protein 1 (PD-1) blockades have been demonstrated to be highly effective against various types of cancer. By blocking PD-1 from binding with their ligands (PD-L1 and PD-L2), the “off” signal to the immune system is inhibited, hence reinvigorating the immune cells to kill tumor cells. To date, despite PD-L1 and PD-L2 both interacting with PD-1, research efforts have only been focused on developing anti-PD-L1 inhibitors. Therefore, the work of this honor project has focused on finding anti-PD-L2 peptides by phage display, with the …

Chemical Control And Understanding Of Horizontal Gene Transfers, Drug-Resistance Development, And Filament And Biofilm Formation, Yuchen Jin

Dissertations - ALL

Biofilms formed by microbes on surfaces are the sources for persistent infectious diseases and environmental problems. The mechanism and details of how antibiotics promote biofilm formation is largely unknown. For instance, it not clear what stages of biofilm growth are promoted to proceed faster than without antibiotics, what phenotypes of bacteria form in an antibiotic-promoted biofilm, and what different biofilm compositions and structures are caused by the presence of antibiotics. Among other effects, antibiotics can cause bacteria to form filaments of living bacteria. Here, we conduct a real-time study of the adherence of bacteria and antibiotic-induced filamentous bacteria on surfaces …

Caribbean Reef-Building Coral-Symbiodiniaceae Network: Identifying Symbioses Critical For System Stability In A Changing Climate, Shaman Patel

All HCAS Student Capstones, Theses, and Dissertations

Increasing global ocean temperatures and frequency of marine heatwaves pose dire consequences for coral reefs. High temperatures often lead to disruptions in coral symbiosis resulting in coral bleaching, increasing the mortality of corals. However, corals can potentially avoid bleaching peril by associating with thermally tolerant symbionts. Here we provide a tool for understanding symbiosis network stability of Caribbean reef-building corals. We created a network of Caribbean hermatypic corals and their associated Symbiodiniaceae phylotypes. A bleaching model was applied to this network to test for resilience and robustness (R50) to thermal stress. It was also layered with trait data for coral …

Sequencing And Functional Characterization Of A Latrodectus Geometricus Defensin, Lg-Defensin, Jacklyn Victoria Thompson

Electronic Theses and Dissertations

Defensins are small, cysteine-rich, immune related proteins described to be the most widespread family of invertebrate antimicrobial peptides. Presently, there is limited information regarding spider defensins. In this study, a new defensin peptide was described in Latrodectus geometricus, Lg-defensin. The full open reading frame was resolved using RACE and de novo assembly, followed by a bioinformatical analysis and phylogenetic alignment to determine conserved sequence patterns and structural similarities to other defensins. Next, the functionality of Lg-defensin was determined using in vitro RNA interference to assess what impact silencing had on the spider’s ability to control a gram-positive and gram-negative bacterial …

The Role Of Fatty Acid Metabolism In The Pathogenesis Of Trypanosoma Brucei, Nava Poudyal

All Dissertations

Trypanosoma brucei is the protozoan parasite that causes African Sleeping Sickness in humans and nagana, a wasting disease in cattle. T. brucei completes its life cycle in two hosts, mammals and the tsetse fly insect vector. Due to the geographical restriction of the tsetse fly, the disease is endemic in sub-Saharan Africa. Both the insect and mammalian forms of the parasite need fatty acids to anchor their surface proteins. We worked on three projects on fatty acid metabolism and its role in immune evasion strategies of T. brucei. First, we assessed the role of T. brucei surface proteins in …

Exploring The Anticancer Mechanism Of Thienopyrazole Derivative Tpz-1 In Acute Myeloid Leukemia, Jessica Dyanne Hess

Open Access Theses & Dissertations

Anticancer drug discovery is a time and resource-consuming process for which exceedingly reliable and efficient modern approaches are needed. Phenotypic drug screenings can generate highly potent and innovative drug candidates; however, deconvolution of the drugâ??s target often presents significant barriers to drug development. To overcome this hurdle, we have originally combined in vitro and in silico analyses to uncover the molecular mechanism(s) driving the anticancer activity of the uniquely structured small molecule drug candidate, Tpz-1. Our study revealed that Tpz-1 is a multitargeted agent which induces the programmed death of HL-60 acute myeloid leukemia cells primarily through disruption of microtubule …

Dna Origami Scaffold Development For Digital Nucleic Acid Memory, Sarah Elizabeth Kobernat

Boise State University Theses and Dissertations

Recently, DNA nanotechnology has emerged as a promising and rapidly expanding method to utilize nucleic acids as a nanoscale building material. DNA origami is a major structural application of DNA nanotechnology, using DNA to construct two- and three-dimensional shapes. These structures have been employed for a variety of uses including DNA data storage. DNA is a promising material to address the impending shortage of silicon-based storage as data demands increase. There are many sequence-based methods of data storage, but digit Nucleic Acid Memory (dNAM) uses DNA origami as a breadboard and is read by super-resolution microscopy instead. dNAM uses DNA …

Structure, Function, And Immunogenic Applications Of Ab5-Type Adp-Ribosylating Bacterial Toxins, Elise Marie Overgaard

Boise State University Theses and Dissertations

Bacterial mono-ADP-ribosyltransferases (ARTs) catalyze the singular transfer of an ADP-ribose moiety from an NAD+ molecule onto a target molecule. ARTs contain an ancient and highly conserved tertiary structure and have a wide variety of intracellular targets and effects. Some, but not all, bacterial ARTs have an AB₅-type multimeric structure consisting of an enzymatically active subunit non-covalently situated atop of a non-toxic pentamer. The active, or A, subunit of AB₅-type toxins has a catalytic action that contributes to bacterial pathogenicity, and it is sometimes, but not always, an ART. ArtAB is an ART with AB₅-type …

Modulation Of Alpha-Crystallin-Membrane Association By Phospholipid Acyl Chain Length And Degree Of Unsaturation, Geraline Trossi-Torres

Boise State University Theses and Dissertations

Cataract is the leading cause of blindness worldwide. The only treatment for cataracts is the surgical removal of the cataractous lens and the replacement of an intraocular lens. With less availability of treatment and low income, the visual damage caused by cataracts can go untreated. The cataract may develop again after surgery, such as posterior capsule opacification. With age and cataracts, α-crystallin, a significant protein of the mammalian eye lens, is progressively associated with the eye lens membrane. The primary association sites of α-crystallin with the membranes are phospholipids. However, it is unclear if phospholipids’ acyl chain length and degree …

The Role Of Vsmc Mir-33a Expression On Apoa-I Mediated Cholesterol Efflux And Macrophage-Like Cell Transdifferentiation, Ikechukwu Esobi

All Dissertations

Atherosclerosis is a condition caused by cholesterol accumulating in arterial intimal cells and is a disease that kills more people in the United States and globally than any other disease. Atherosclerosis is commonly recognized to arise from arterial intimal macrophage cholesterol accumulation, but cell lineage tracing technology has shown that a large majority of cholesterol-laden intimal cells found in atherosclerotic arteries are actually vascular smooth muscle cells that have switched phenotypes to a macrophage-like cell. This vascular smooth muscle cell to macrophage-like cell phenotypic switch is known as transdifferentiation and can be triggered by vascular smooth muscle cell cholesterol accumulation. …

Functional Characterization Of The Newly Discovered Type V Crispr-Cas Protein Cas12a2, Dylan J. Keiser

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Similarly to people, bacteria are under the treat of infection by viruses. To circumvent these threats, bacteria evolve complex immune systems. Our understanding of some of these immune systems has led to many advancements in the field of Biotechnology including tools that made expressing proteins for study in a lab easier, tools that revolutionized the feasibility of gene editing, and tools that could change the way we think about viral diagnostics and cancer therapeutics. A certain type of immune system that bacteria use to fight virus is called a CRISPR system. Presented here is work to understand the function of …

A Novel Transmembrane Ligand Inhibits T Cell Receptor Activation, Yujie Ye

Doctoral Dissertations

T lymphocytes (T cells) play essential roles in the adaptive immune system. Each mature T cell expresses one type of functional T cell receptor (TCR). The TCR recognizes antigens bound to the major histocompatibility complex (MHC) in antigen presenting cells. The resulting stimulation signal crosses the transmembrane domain of TCR and initiates downstream signaling cascades. The human immune system relies on TCRs to recognize a variety of pathogens. Normally, TCR can distinguish the self-antigens from pathogenic antigens. However, dysfunction or aberrant expression of TCRs causes different inflammatory and autoimmune diseases, which afflict millions of people annually (Chapter I). Current treatments …