Molecular Biology Commons^™

Trip13’S Crucial Role In Pancreatic Cancer Progression, Swati Dhasmana, Anupam Dhasmana, Stella Rios, Iris A. Enriquez-Perez, Sheema Khan, Farrukh Afaq, Upender Manne, Murali M. Yallapu, Subhash Chauhan

Research Symposium

Background: Pancreatic cancer, characterized by its high mortality rate, stands as one of the most aggressive cancer forms. The projected surge in pancreatic cancer-related deaths, making it the second leading cause in the United States by 2030, underscores the urgency for effective early screening tools. This study employs data mining methods to scrutinize bioinformatic data surrounding TRIP13. Examining differential expression across various cancers, correlating TRIP13 expression with pancreatic cancer stages, exploring associations with common cancer genes, and analyzing overall survival rates constitute the core investigations. Integrated with molecular biology techniques, the study further quantifies TRIP13 expression in progressive pancreatic cancer …

Proteomic Analysis Of Stress Associated Factor Overexpression In Hepatocellular Carcinoma, Mohammad Shabir Hussain, Sophia Leslie, Amayrani Sanchez, Samantha Lopez, Kyle Doxtater, Manish Kumar Tripathi

Research Symposium

Background: Hepatocellular carcinoma (HCC) constitutes a substantial portion, accounting for 85% to 90% of liver cancers worldwide. Notably, within the Hispanic population, liver cancer mortality rates are notably higher, particularly evident in regions like the South Texas Rio Grande Valley (RGV), where nearly 90% of the populace is Latino/Hispanic. This region grapples with poverty affecting nearly 30% of its residents, coupled with elevated rates of obesity, diabetes, and low-income households, thereby fostering a prevalent environment of stress. Stress can profoundly impact cancer outcomes by compromising immune functionality and triggering inflammatory responses, potentially impairing surveillance against oncogenic triggers. The activation of …

Remodeling Anaplastic Thyroid Cancer's Aggressive Profile And Metabolic Signature By Natural Alkaloid Berberine, Tara Elizabeth Jarboe

NYMC Student Theses and Dissertations

Anaplastic thyroid cancer is a rare, fatal cancer with a five-year survival of 4%. Universally diagnosed at stage IV, anaplastic thyroid cancer is characterized by its lack of differentiation, rapid proliferative rate, highly inflammatory tumor microenvironment, and metabolic dysregulation. Refractory to all established therapies, anaplastic thyroid cancer requires a novel therapeutic approach that targets all of these drivers of anaplastic thyroid cancer carcinogenesis. We propose natural alkaloid berberine as a therapeutic with multitarget efficacy to alter mitochondrial metabolism and reprogram anaplastic thyroid cancer’s aggressive phenotype. Our in vitro model uses monocyte cell line U937, anaplastic thyroid cancer cell lines T238 …

An Rnai-Based Approach To Ips Calligraphus Management: A Promising Strategy For Forest Protection, Mary Wallace

Theses and Dissertations--Entomology

As climate change leads to more frequent and severe extreme weather, host tree stress is increasing the occurrence of large-scale bark beetle outbreaks. One such beetle, Ips calligraphus (Germar), a native bark beetle in the southeastern United States, has traditionally been considered a secondary pest of pine trees. Management has relied on silvicultural practices that enhance forest resilience, enabling host trees to effectively use natural defenses to deter beetle infestation. However, during periods of forest stress caused by storms, droughts, human disturbance, and other factors, beetle outbreaks can cause considerable ecological and economic damage.

Addressing worsening I. calligraphus outbreaks will …

Abl1/2 And Ddr1 Cooperate To Stabilize Braf/Craf To Drive Erk1/2 Reactivation And Promote Mek Inhibitor Resistance In Nras-Mutant Melanomas, Anastasia Lyon

Theses and Dissertations--Pharmacology and Nutritional Sciences

This study addresses the escalating incidence of NRAS-mutant melanomas, a type of skin cancer lacking FDA-approved targeted therapies. Despite ongoing research targeting the RAF/MEK/ERK pathway, existing drugs fail to enhance progression-free survival due to acquired resistance. This project identifies a novel role for ABL1/2 and DDR1 kinases in driving drug resistance and proliferation of NRAS-mutant melanoma cells. ABL1/2 and DDR1 cooperate to promote RAF homodimerization and protein stability in order to reactivate MEK/ERK signaling to drive MEK1/2 inhibitor (MEKi) resistance and promote survival of resistant cells. By targeting ABL1/2 and DDR1 with nilotinib, a FDA-approved anti-leukemic inhibitor, we …

Practical Challenges In Delivering Dsrna For Woody Plant Protection, Zachary Bragg

Theses and Dissertations--Entomology

Unprecedented weather events associated with climate change, coupled with extensive anthropogenic stresses, have reduced the effectiveness of traditional forest pest management approaches, which can no longer keep pace with invasive species overwhelming naïve landscapes and native pests experiencing eruptive and expansive outbreaks. Double-stranded RNA-(dsRNA) mediated gene silencing, a type of RNA interference (RNAi), has been coopted for use as a biopesticide against a multitude of agricultural and horticultural pests and could serve as a powerful tool for woody plant protection. While effective initiation of gene silencing and subsequent mortality have been demonstrated in multiple tree pests, effective and efficient methods …

A Multimolecular Perspective On The Success Of Wolf Recovery And Relocation, Samuel D. Hervey

Dissertations, Master's Theses and Master's Reports

With global biodiversity in decline and many species isolated in fragmented habitats, conservation efforts increasingly rely on natural recolonization and translocation to restore ecosystems. These strategies face challenges such as genetic erosion and habitat limitations, highlighting the need for effective monitoring practices. This research assesses the success of wolf recovery initiatives by examining long-term genetic and genomic health using both traditional and advanced molecular methods. First, we investigated the genetic health of 19 gray wolves (Canis lupus) relocated to Isle Royale National Park to restore ecosystem balance. Initial genetic assessments with microsatellites found that these wolves had genetic diversity metrics …

The Evolution Of The Metazoan Circadian Molecular Mechanism And The Conservation Of Canonical Circadian Elements, Olivia Waldridge

Theses and Dissertations--Biology

The temporal organization of biological activities through circadian rhythms is pivotal for the survival of organisms. Significant progress has been made in understanding the molecular foundations of animal circadian clocks through the characterization of key components such as Clock, Bmal1/Cycle(Cyc), Period (Per), Timeless, and Cryptochrome (Cry) in several model organisms. To determine the universality of this conservation, we investigated the sequences of these genes and their paralogs across 46 animal species that encompass multiple phyla in the metazoan kingdom to resolve the relative timing of duplication and loss events that have diversified core clock components in the metazoan kingdom. Using …

Exploring 3d Genome Interaction And Epigenetic Regulation Via Swi/Snf Complex And Deep Learning Models, Ruoyun Wang

Dartmouth College Ph.D Dissertations

The three-dimensional organization of the genome is fundamental in regulating gene expression and maintaining cellular function. This organization's complexities, influenced by epigenetic marks and chromatin remodeling complexes, are crucial for understanding genomic regulation. Among these, the SWI/SNF complexes are key, facilitating chromatin accessibility and regulating gene activity across cell types. The first part of my dissertation focuses on SWI/SNF complexes, exploring their role in chromatin remodeling and their impact on 3D genome architecture. Utilizing next-generation sequencing (NGS) techniques, this section investigates the interplay between these complexes and chromatin structure. During my research on the SWI/SNF complex, I was intrigued by …

Characterizing 4,4’-Methylene Diphenyl Diisocyanate Exposure In Primary Human Epidermal Keratinocytes: A Multi-Omics Approach, Brandon F. Law

Graduate Theses, Dissertations, and Problem Reports (ETD)

Exploring the routes of exposure and biological fate of 4,4’-methylene diphenyl diisocyanate (MDI) has been a challenge for many years. Occupational exposure to MDI can result in the development of occupational asthma (MDI-OA) which results in loss of productivity, large economic costs, and costs to the individual worker. Initially, it was thought that respiratory exposure to MDI was the most likely route leading to MDI-OA. Industries utilizing MDI have been successful at controlling airborne concentrations according to industrial hygiene assessment and newly diagnosed cases of MDI-OA decreased and plateaued. New research suggests that dermal exposures to MDI may explain this …

Using In Silico Tools To Analyze The 5ʹ Untranslated Regions Of The Alcohol Dehydrogenase Gene From Arabidopsis Thaliana And Omega Sequence, Reza Mohammadhassan, Tina Asadishad

Makara Journal of Science

The 5ʹ ends of protein-encoding genes contain 5ʹ untranslated regions (5ʹUTRs), which can effectively participate in regulating gene expression. The 5ʹUTRs of Arabidospis thaliana–derived alcohol dehydrogenase gene (AtADH) and omega (Ω) sequence from tobacco mosaic virus (TMV) are the most effective enhancers in biotechnology. In this study, bioinformatics techniques were employed to analyze the characteristics of the above sequences. After 5ʹUTR sequence collection, the inner ribosome entrance sites; small RNA (sRNA) target sequences; nucleotide contents; and upstream start and stop codons, ORFs, and coding DNA sequences of the Ω sequence and AtADH 5ʹUTR were identified. Moreover, the …

Increased Coding Potential Of Bovine Herpesvirus 1, Victoria Jefferson

Theses and Dissertations

Bovine respiratory disease (BRD) costs the cattle industry millions of dollars in costs in treatment and loss every year in the United States. A significant pathogen often contributes to BRD is Bovine Herpesvirus 1 (BoHV-1), a double stranded DNA virus with the ability to establish latency in the trigeminal ganglia and neurons. Primary infection with BoHV-1 results in immunosuppression that increases the risk of secondary bacterial infection and pneumonia. Because herpesviruses infect their hosts for life and can be reactivated in times of stress, BoHV-1 can present a recurring risk of BRD. The following research aims to expand the knowledge …

A Cancer-Specific Study On The Differentially Expressed Protein-Protein Interactions Of Fumarate Hydratase, Sydney Lac

Dissertations and Theses (Open Access)

Fumarate hydratase (FH) is an enzyme used in the Krebs Cycle to convert fumarate to malate, and it is controlled by the FH gene. In this paper, we will investigate its role in Uterine Corpus Endometrial Carcinoma (UCEC) and how FH-deficient cells affect tumorigenesis. It is well-established that FH has been extensively studied in connection with renal cell carcinoma, skin and uterine leiomyomas, pheochromocytoma, and paraganglioma. However, we aim to construct an interaction network of significant genes related to the FH gene under conditions of FH deficiency in the Kreb Cycle. Creating an interactive network that illustrates the interconnectedness of …

Flavonol Glucosylation: A Structural Investigation Of The Flavonol Specific 3-O Glucosyltransferase Cp3gt, Aaron S. Birchfield

Electronic Theses and Dissertations

Flavonoid glycosyltransferases (GTs), enzymes integral to plant ecological responses and human pharmacology, necessitate rigorous structural elucidation to decipher their mechanistic function and substrate specificity, particularly given their role in the biotransformation of diverse pharmacological agents and natural products. This investigation delved into a comprehensive exploration of the flavonol 3-O GT from Citrus paradisi (Cp3GT), scrutinizing the impact of a c-terminal c-myc/6x histidine tag on its enzymatic activity and substrate specificity, and successfully achieving its purification to apparent homogeneity. This established a strong foundation for potential future crystallographic and other structure/function analyses. Through the strategic implementation of site-directed mutagenesis, a thrombin …

Spatial Structure Formation By The Post-Transcriptional Gene Regulator Rsme In Pseudomonas Fluorescens Pf0-1, Anton Evans

Electronic Theses and Dissertations

Microorganisms are often found in microbial communities we call biofilms. Organisms living in these crowded environments have significant evolutionary pressure to retain access to the resources necessary to sustain life. My research uses the bacterium Pseudomonas fluorescens Pf0-1 to study how organisms evolve strategies to solve this crowding problem as aging colonies repeatedly generate mutant patches. These mutants expand the reach of the colony resulting in decreased local density as they push themselves up to the resource rich surface. These spatial structures result from social interactions between the mutant and the parental cells mediated through extracellular secretions, resulting in the …

Multiphasic Molecular Mechanisms Regulate Expression Of Interleukin 1Β, As Well As Other Immediate-Early Genes, In Monocytes And Macrophages, David Macar

Electronic Theses and Dissertations

Interleukin 1β (IL-1β), an important cytokine in both health and disease, functions as a major proinflammatory mediator of pathological challenges, including involvement in the cytokine storm associated with Macrophage Activation Syndrome, Hemophagocytic Lymphohistiocytosis and the severe secondary effects of SARS-CoV-2 infection. Therapeutic approaches to limiting the effects of IL-1β protein have focused either on specific protein neutralization before release from activated macrophages (by general metabolic inhibitors and inflammasome inhibition) or after release by ligand and receptor obstruction (e.g., Canakinumab, Anakinra and Rilonacept). Although these approaches are efficacious, they inhibit steps after gene expression. Since a single gene expresses …

Structural Diversity And Stress Regulation Of The Plant Immunity-Associated Calmodulin-Binding Protein 60 (Cbp60) Family Of Transcription Factors In Solanum Lycopersicum (Tomato), Vanessa Shivnauth, Sonya Pretheepkumar, Eric J. R. Marchetta, Christina A. M. Rossi, Keaun Amani, Christian Castroverde

Biology Faculty Publications

Cellular signaling generates calcium (Ca2+) ions, which are ubiquitous secondary messengers decoded by calcium-dependent protein kinases, calcineurins, calreticulin, calmodulins (CAMs), and CAM-binding proteins. Previous studies in the model plant Arabidopsis thaliana have shown the critical roles of the CAM-BINDING PROTEIN 60 (CBP60) protein family in plant growth, stress responses, and immunity. Certain CBP60 factors can regulate plant immune responses, like pattern-triggered immunity, effector-triggered immunity, and synthesis of major plant immune-activating metabolites salicylic acid (SA) and N-hydroxypipecolic acid (NHP). Although homologous CBP60 sequences have been identified in the plant kingdom, their function and regulation in most species remain unclear. In …

Exploring The Interactions Between Sars-Cov-2 And Host Proteins, Sojan Shrestha

School of Biological Sciences: Dissertations, Theses, and Student Research

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current pandemic, Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 is considered to be of zoonotic origin; it originated in non-human animals and was transmitted to humans. Since the early stage of the pandemic, however, the evidence of transmissions from humans to animals (reverse zoonoses) has been found in multiple animal species including mink, white-tailed deer, and pet and zoo animals. Furthermore, secondary zoonotic events of SARS-CoV-2, transmissions from animals to humans, have been also reported. It is suggested that non-human hosts can act as SARS-CoV-2 reservoirs where accumulated …

Functional Domains Of The Hsv-1 Ul37 Protein In Virus Infectivity And Retrograde Transport In Neurons, Carolyn Clark

LSU Doctoral Dissertations

Herpes simplex virus type 1 is large alphaherpesvirus with 20 envelope proteins and 23 tegument proteins. Virus entry is via fusion of the viral envelope with cellular membranes mediated by a complex of viral glycoproteins. Glycoprotein B (gB) is the only fusogenic glycoprotein, while other viral glycoproteins and membrane proteins including gD, gH, gL, gK and UL20 membrane protein modulate gB’s fusogenicity. Previously, Our laboratory developed the HSV-1 (VC2) vaccines strain with partial deletions in the amino termini of gK (ΔgK(31–68)) and the UL20 membrane protein (ΔUL20(4–22)). VC2 enters epithelial cells only via endocytosis followed by release of the capsid …

Dna Methylation And The Response To Infection In Introduced House Sparrows, Melanie Gibson

College of Graduate Studies: Theses & Dissertations

Epigenetics is the study of molecular modification of a genome without changing its base pairs. The most studied type of epigenetic mechanism is DNA methylation, which is capable of turning a gene “on” or “off.” Epigenetic potential is the capacity to which an individual can have methylation on its genome. The more CpGs available, the greater the epigenetic potential. In invasive species, genetic variation has been observed to be paradoxical: not much of it exists on a genomic level, but epigenetically, phenotypic variation can occur. The focus on shift in gene expression in this study is on Toll-Like Receptor 4 …

Effects Of Depth, Distance To Shore, And Water Velocity On Organismal And Extra-Organismal Environmental Dna Concentrations In A Large River, Dylan Keel

Cal Poly Humboldt theses and projects

Environmental DNA (eDNA) is a sensitive tool for detection of aquatic species and concentrations of eDNA in water samples have been useful for estimating abundance. This study evaluated the effects of depth, distance to shore, and water velocity on the concentration of organismal and extra-organismal eDNA concentrations in the Klamath River, California (basin area ≅ 40,000 km²). At each of six river cross sections 32 water samples were collected, including surface samples and depth samples evenly distributed across the cross section, and eDNA concentrations were determined for the parasite Ceratonova shasta and Chinook salmon, Oncorhynchus tshawytscha, using …

Identification Of Novel Biosynthetic Gene Clusters Encoding For Polyketide/Nrps-Producing Chemotherapeutic Compounds From Marine-Derived Streptomyces Hygroscopicus From A Marine Sanctuary, Hannah Ruth Flaherty

Honors Theses and Capstones

Nearly one out of six deaths in 2020, around ten million people, were caused by cancer, making it a leading cause of death worldwide (WHO, 2022). This major public health issue, in addition to the rise of multidrug-resistant (MDR) pathogens, provides a high demand for the discovery of new pharmaceutical drugs to be used clinically to treat these conditions. The Streptomyces genus accounts to produce 39% of all microbial metabolites currently approved for human health, indicating its potential as an important species to study for antimicrobial and anticancer agents. The long linear genome of Streptomyces contains specialized sequences known as …

Generation Of Chimeric Rhinoviruses Presenting Sars-Cov-2 Broadly Neutralizing Epitopes And Their Antigenicity Characterization, Danish Ansari

Biotechnology Theses

The global COVID pandemic is not yet fully under control as there were over 21 million new cases of SARS-CoV-2 infections and over 50,000 deaths globally as of January of 2022. A heavily mutated variant of concern, Omicron is responsible for most of these cases which demands an urgency for a new vaccine. NIH reports over 180 vaccine candidates that use various strategies currently in development. However, a recurring concern with these vaccines is that the continuous viral mutations decrease the efficacy of vaccines. Therefore, we proposed to construct a human rhinovirus (HRV) based chimeric virus containing highly conserved, broadly …

Cell Signaling And Stress Response In The Yeast Saccharomyces Cerevisiae: A Study Of Snf1, Scott E. Arbet Ii

Graduate Theses, Dissertations, and Problem Reports (ETD)

Saccharomyces cerevisiae are yeast that are unicellular eukaryotic organisms that are well studied as a model organism for understanding fundamental cellular processes. The ability of yeast to sense nutrient availability is crucial for their survival, growth, and reproduction. Yeast cells use various mechanisms to sense and respond to nutrient availability, including transporter-mediated uptake, receptor-mediated signaling, and sensing of metabolites. The subcellular localization of nutrient-sensing components is crucial for yeast function in nutrient sensing and signaling. Protein complexes, such as the AMP-activated protein kinase (AMPK) pathway, in nutrient sensing and response, as well as the downstream effects of these pathways …

From Culture To Metagenomics: A Comprehensive Evaluation Of The Female Reproductive Tract Microbiome In Pregnancy, Jonathan Panzer

Wayne State University Dissertations

The advent of Next Generation Sequencing technologies prompted novel investigations of the microbiome. These revealed both increased diversity of known microbiomes such as those of the gut, oral cavity and vagina, but also bacterial DNA in tissues previously considered sterile such as the blood, liver, brain, and placenta. Thus, previous paradigms of sterility, based primarily on culture data, were called into question. However, interpretation of bacterial DNA signals from low-microbial biomass tissues is complex due to the strong potential for contamination and interference from the surrounding environment. Yet, many new methodologies are being developed to help isolate valid bacterial DNA …

The Antimicrobial Resistance Plasmid Mobilome Of Salmonella Enterica And Related Enteric Species And Factors That Influence The Transfer Efficiency., Suad Algarni

Graduate Theses and Dissertations

The dynamic distribution of antimicrobial resistance genes in Salmonella enterica is considered a public health risk. S. enterica is one of the most important etiological agents of foodborne illness and has a critical impact on global human health. In S. enterica and related species, mobile genetic elements (MGEs) serve as primary vehicles for the dissemination of antibiotic resistance genes in the bacterial evolution. This dissemination can be impacted by different selective pressures that leads to diverse antibiotic response phenotypes. This project focusses on the dynamics of antimicrobial resistance genes, particularly exploring the transfer efficiency of multidrug resistance plasmids in S. …

Using The Embl-Ebi Clustal Omega Tool To Calculate Diversity Of Heavy Chain Phage-Display Libraries, Michael Bodri, Shane A. Webb

Georgia Journal of Science

Here we show that traditional Sanger sequencing combined with analysis tools available from the European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), specifically EMBOSS Transeq and Clustal Omega, is extremely effective in the analysis of naïve phage display antibody libraries for the determination of library size and diversity. The free tools are easy to use and require little manipulation of reads by hand, allowing analysis to be performed on a standard personal computer. Utilization of this technique has applicability to researchers with limited access to deep sequencing. The primary drawback to this analysis methodology is that antibodies with particular molecular or …

Ngly1 Deficiency Affects Glycosaminoglycan Biosynthesis And Wnt Signaling Pathway In Mice, Amy Batten

PANDION: The Osprey Journal of Research and Ideas

Individuals affected by NGLY1 Deficiency cannot properly deglycosylate and recycle certain proteins. Even though less than 100 people worldwide have been diagnosed with this rare autosomal recessive condition, thousands are affected by similar glycosylation disorders. Common phenotypic manifestations of NGLY1 Deficiency include severe neural and intellectual delay, impaired muscle and liver function, and seizures that may become intractable. Very little is currently known about the various mechanisms through which NGLY1 deficiency affects the body and this has led to a lack of viable treatment options for those afflicted. This experiment uses a loss-of-function (LOF) mouse model of NGLY1 Deficiency homologous …

Transcriptional Mechanisms Of Neuroprotection In Excitotoxicity Driven Neurodegeneration In C. Elegans, Zelda Z. Mendelowitz

Dissertations, Theses, and Capstone Projects

Excitotoxicity is notorious for triggering neuronal cell death in both developmental and adult-onset neurodegenerative diseases. In excitotoxicity, excessive concentrations of Glutamate in the synapse overstimulate Glutamate Receptors (GluRs) on postsynaptic neurons. While GluR mediated degenerative mechanisms remain obscure, GluR activation was surprisingly found to also have a neuroprotective effect through activation of specific transcriptional programs. To identify evolutionarily conserved transcriptional programs in neuroprotection we use a C. elegans model of excitotoxic necrosis (glt-3;nuIs5). We have identified that non-canonical activation of the transcription factor CRH-1/CREB mediates neuroprotection in our excitotoxicity model. We found the Histone Acetyl Transferase, MYS-1/KAT6, and the neuronal …

Comparative Genomics And Virulence Studies Of Streptomyces Soil Rot And Scab Pathogen Species, Natasha Soares

LSU Doctoral Dissertations

Comparative genomic analyses were performed to gain insights into the organization and content of the genome of Streptomyces ipomoeae, the soil rot pathogen that infects sweetpotatoes. Unlike Streptomyces scab pathogens, the thaxtomin phytotoxin gene cluster (txt) in S. ipomoeae does not appear to reside within a genomic island and has diverged from its scab pathogen counterparts. Increased usage of the rare TTA codon, particularly for the txt cluster, suggests greater translational control by the bldA tRNA in S. ipomoeae. Orthologous gene searches and secondary metabolite profiling yielded ortholog groups and metabolite gene clusters that were exclusive …