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Full-Text Articles in Life Sciences

Characterizing And Epitope Mapping Single-Domain Antibodies On Borrelia Burgdorferi Protein Ospa, Saiful Basir Dec 2022

Characterizing And Epitope Mapping Single-Domain Antibodies On Borrelia Burgdorferi Protein Ospa, Saiful Basir

Legacy Theses & Dissertations (2009 - 2024)

Epitope mapping a protein that enables pathogenesis is crucial for the development of therapies and prophylactics that can inhibit the pathogen’s function and its transmission of disease. The lipoprotein OspA enables Lyme Disease etiologic pathogen, Borrelia burgdorferi, to inhabit the tick midgut until transmission occurs. Anti-OspA mAbs and their smaller VHH counterparts are highly specific and tailored to bind proteins such as OspA, reproducibly, at established binding sites or epitopes. Previous studies found an array of mAbs that successfully bound OspA and have already been used in epitope mapping. To our knowledge, this is the first use of VHHs in …


Understanding SjöGren's Syndrome As A Systemic Autoimmune Disorder, Gaietchyne Chery Dec 2022

Understanding SjöGren's Syndrome As A Systemic Autoimmune Disorder, Gaietchyne Chery

Legacy Theses & Dissertations (2009 - 2024)

Sjögren’s syndrome is an autoimmune condition characterized by a dysfunction in the lachrymal and salivary glands which results in dry eyes and dry mouth. Since its first description in 1892, the disease is one of the most common autoimmune diseases after lupus erythematosus and rheumatoid arthritis in the United States. Despite its high prevalence in the general population, Sjögren’s syndrome remains hard to diagnose due to the wide range of symptoms associated with the disease that is also shared by other conditions. Furthermore, the mechanisms behind the pathogenesis are not properly understood even though multiple factors have been proposed to …


Vircy-Seq : A Protocol For Characterizing Viral Activity, Tyler James Dion Dec 2022

Vircy-Seq : A Protocol For Characterizing Viral Activity, Tyler James Dion

Legacy Theses & Dissertations (2009 - 2024)

The main purpose of pharmaceutical production is to produce safe effective medicine for patient use. In an effort to ensure patient safety constant surveillance for viruses takes place. The detection of a viral nucleic acid in a pharmaceutical production setting results in investigations to assess its infectious potential. This is an intensive, expensive process that entails many tests such as the observation of hemadsorption, cytopathic effects (CPE), and more. These tests are typically specific and only capture certain viruses, as factors like CPE can only be observed in some viral species. A new investigational method that is effective on all …


Development Of Nucleic Acid Diagnostics For Targeted And Non-Targeted Biosensing, Christopher William Smith Dec 2022

Development Of Nucleic Acid Diagnostics For Targeted And Non-Targeted Biosensing, Christopher William Smith

Legacy Theses & Dissertations (2009 - 2024)

The field of nucleic acid technology is rapidly expanding with new impactful discoveriesbeing made each year. Starting from the discovery of the double-helix structure, cloning, gene editing, polymerase chain reaction (PCR), CRISPR technology, and even the late mRNA vaccines; nucleic acid technology is at the forefront of improving medicine. Nucleic acid technology is extremely versatile due to its easy programmability, automated cheap synthesis, and even its catalog for numerous chemical modifications that can be used to alter structure stability. For example, the number of permutations that can be made with DNA just by altering the code for adenine (A), cytosine …


An Ims-Ms/Md Workflow For Determining Higher Order Structure And Dynamics Of Nucleic Acids, Rebecca D'Esposito Aug 2022

An Ims-Ms/Md Workflow For Determining Higher Order Structure And Dynamics Of Nucleic Acids, Rebecca D'Esposito

Legacy Theses & Dissertations (2009 - 2024)

Ion mobility spectrometry - mass spectrometry (IMS-MS) has potential for the investigation of structure and dynamics in large biopolymers, which will come to full fruition only with a firmer understanding of how to interpret the experimental data. Numerous studies have employed elements of nucleic acid (NA) secondary structure, such as duplexes and hairpins, to explore the relationships between structure, experimental conditions, and actual observations. When combined with molecular dynamics simulations (MDS), IMS-MS can be effectively employed to perform structural elucidation of biomolecules that are not readily amenable to established techniques employed for structural analysis.


Parallel Networks That Govern The Transcriptional Response To Stress, Serene Anne Durham Aug 2022

Parallel Networks That Govern The Transcriptional Response To Stress, Serene Anne Durham

Legacy Theses & Dissertations (2009 - 2024)

The transcription factor, p53, plays a pivotal role in the oversight of many stimulus-dependent pathways. Its ability to respond to a wide variety of cellular stress stimuli by activating a broad range of target genes has led it to be characterized as a stress-dependent transcription factor. Our research focuses on deconvoluting the varied transcriptional response to distinct stress signals in an attempt to define the regulatory strategies leading to gene activation after cell stress. We have found that distinct stress response networks, some of which are p53-independent, are converging at activation of a common set of target genes. Our data …


N6-Methyladenosine Rna Modifications In Myogenesis / Narrative Competence And Cognitive Mapping As A Culturally Sustaining Pedagogy In The Education Of Emergent Bilinguals, Marina Danielle Infantado Aug 2022

N6-Methyladenosine Rna Modifications In Myogenesis / Narrative Competence And Cognitive Mapping As A Culturally Sustaining Pedagogy In The Education Of Emergent Bilinguals, Marina Danielle Infantado

Legacy Theses & Dissertations (2009 - 2024)

Myogenesis involves skeletal muscle stem cells (MuSCs) that produce and regenerate skeletal muscle during regular growth and repair. However, when this system fails to function normally, it can lead to musculoskeletal diseases like Duchenne Muscular Dystrophy (DMD). Therefore, it is important to study the molecular mechanisms behind this developmental process in order to seek therapies and solutions for these types of diseases. Our interest lies in the field of epitranscriptomics, which focuses on post-transcriptional ribonucleic acid (RNA) modifications, particularly N6-methyladenosine (m6A), which involves the addition of a methyl group to the adenosine nucleotide, a process that is mediated by the …


Amyloid Fibril Formation And Polymorphism : A Critical Role Of Sulfur-Containing Amino Acid Residues, Tatiana Quiñones-Ruiz Aug 2022

Amyloid Fibril Formation And Polymorphism : A Critical Role Of Sulfur-Containing Amino Acid Residues, Tatiana Quiñones-Ruiz

Legacy Theses & Dissertations (2009 - 2024)

Protein aggregation that results in the formation of amyloid fibrils has been linked to many neurodegenerative disorders, including Alzheimer’s disease and Parkinson’s disease. The sulfur atoms in methionine (Met) and cysteine (Cys) residues of proteins can be readily oxidized, significantly affecting their properties. Oxidation of sulfur-containing amino acids has recently been shown to affect protein fibrillation. This work presents novel findings on Cys and Met redox reactions that are related to the formation of amyloid fibrils and on the polymorphism of a model fibrillogenic protein, hen egg white lysozyme (HEWL). Biophysical techniques including Raman spectroscopy, atomic force microscopy, electron paramagnetic …


Characterization Of The Role Of The Replicase And Quasispecies Diversity In Flaviviral Evolution And Host Adaptation, Haley Caldwell May 2022

Characterization Of The Role Of The Replicase And Quasispecies Diversity In Flaviviral Evolution And Host Adaptation, Haley Caldwell

Legacy Theses & Dissertations (2009 - 2024)

Flaviviruses include several emerging and re-emerging arboviruses that cause millions of infections each year. Although relatively well-studied, much remains unknown regarding the mechanisms and means by which these viruses adapt to different hosts and rapidly alternate between hosts. Different aspects of flaviviral biology impact host switching, viral fitness, and the generation of viral diversity during genome replication by the NS3 and NS5 proteins. Together these factors may impact host plasticity.


Exploring The Roles Of Stress, Codon Usage, And Rna Modifications In Myotonic Dystrophy Type 1, Afrooz Golestanian Jan 2022

Exploring The Roles Of Stress, Codon Usage, And Rna Modifications In Myotonic Dystrophy Type 1, Afrooz Golestanian

Legacy Theses & Dissertations (2009 - 2024)

Myotonic dystrophy (DM), the most common form of muscular dystrophy, is a neuromuscular disease caused by microsatellite repeat expansions. It can represent a multi-systemic autosomal dominant disease with DM1 and DM2 subtypes. A cytosine-thymine-guanine (CTG) triplet repeat in the 3’ untranslated region (3’UTR) of myotonic dystrophy protein kinase (DMPK) gene causes DM1 disease, which leads to the production of a longer, abnormal and toxic mRNA. The toxic DMPK mRNA sequester the splicing proteins such as Muscle blind-like (MBNL) and rbFOX which leads to gene expression alteration. Repeat associated non-AUG (RAN) translation also occurs in DM1. Mitochondrial dysregulation has also been …


Synthesis Of Oligonucleotides Containing Unnatural Backbone And Regulation Of Crispr Activity Using Inverse Electron Demand Diels-Alder Chemistry, Alyssa Hoy Jan 2022

Synthesis Of Oligonucleotides Containing Unnatural Backbone And Regulation Of Crispr Activity Using Inverse Electron Demand Diels-Alder Chemistry, Alyssa Hoy

Legacy Theses & Dissertations (2009 - 2024)

This thesis describes the synthesis of an oligonucleotide containing an unnatural neutralbackbone. The backbone was constructed using bio-orthogonal inverse electron demand Diels- Alder chemistry between trans-cyclooctene (TCO) and tetrazine (Tz). A TCO phosphoramidite was synthesized and attached to solid support for strand propagation. Uridine monomers containing either bis-TCO or bis-Tz were also synthesized. The oligonucleotide strand was formed by sequential ligation of the bis-Tz and bis-TCO monomers. The oligonucleotide was analyzed using mass spectrometry. This thesis also describes the synthesis of sgRNAs containing non-canonical nucleobases, m1A, m6A, s2U and s4U using the ‘split-and-click’ methodology. The synthetic sgRNAs were assembled using …


Salivary Gland Stromal Heterogeneity And Epithelial Controls, Nicholas L. Moskwa Jan 2022

Salivary Gland Stromal Heterogeneity And Epithelial Controls, Nicholas L. Moskwa

Legacy Theses & Dissertations (2009 - 2024)

Organogenesis is the process organs go through where cellular communications coordinate all a developing organ needs. What organs need are more cells, in the right place, doing the right job. In the salivary gland, we know that stromal cells are important for organogenesis and that they coordinate the epithelium’s form and functions. However, specific stromal contributions have focused on epithelial quantity and placement. There is less information about how the stroma directs the epithelium towards certain functions. Here we used organoids as a model for understanding what stromal signaling directs epithelial cell fate. We found that stromal cell state is …