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Biochemistry, Biophysics, and Structural Biology

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Articles 31 - 60 of 370

Full-Text Articles in Molecular Genetics

Effects Of Microplastic Biofilms On An Anthropogenically Impacted Suburban Lake, Paris M. Velasquez Sep 2024

Effects Of Microplastic Biofilms On An Anthropogenically Impacted Suburban Lake, Paris M. Velasquez

Masters Theses

Plastics have been observed in every location on the planet, and their prevalence in the environment is due in part to their strong resistance to degradation. Inland lakes are susceptible to plastic pollution by highway runoff, which contains plastic fragments of brake pads, car tires, litter, and road paint. These plastics eventually enter freshwater environments and degrade into microplastics (


Developing Coexpression Systems To Introduce Hydroxyproline Into Protein Engineered Collagen Peptides Utilizing Hydroxylase From Acanthamoeba Polyphaga Mimivirus, Jennifer Soldatich Sep 2024

Developing Coexpression Systems To Introduce Hydroxyproline Into Protein Engineered Collagen Peptides Utilizing Hydroxylase From Acanthamoeba Polyphaga Mimivirus, Jennifer Soldatich

Theses and Dissertations

A major challenge of developing collagen mimetic peptides (CMPs) by bacterial expression is to include hydroxyproline for biomedical applications. Coexpression of Prolyl-4-hydroxylase from A.mimivirus with CMPs was investigated. Additionally, four expression designs were created for potential applications in mammalian cells to utilize their natural ability of proline-hydroxylation by post-translational modification.


The Seat Of Singular Gene Choice: Dissecting The Role Of Odorant Receptor Enhancer Elements That Lead To Mammalian Olfactory System Expression, Alessandro M. Rosa Sep 2024

The Seat Of Singular Gene Choice: Dissecting The Role Of Odorant Receptor Enhancer Elements That Lead To Mammalian Olfactory System Expression, Alessandro M. Rosa

Dissertations, Theses, and Capstone Projects

Odorant receptors (ORs) were first identified in 1991 and the initial data strongly suggested that ORs were part of a large superfamily of G-protein-coupled receptors. Within a few years of the discovery of the OR superfamily, it became clear that each OR allele was exclusively expressed in olfactory sensory neurons (OSN), and that this singular expression leads to cellular identity. Many studies over the past thirty years have sought to unlock the mysteries of the mechanism for monoallelic and monogenic OR gene activation and expression in OSNs, however no definitive model for singular gene expression has emerged.

Using a series …


Emerin Deficiency Drives Mcf7 Cells To An Invasive Phenotype, Emily Hansen, Christal Rolling, Matthew Wang, James M Holaska Aug 2024

Emerin Deficiency Drives Mcf7 Cells To An Invasive Phenotype, Emily Hansen, Christal Rolling, Matthew Wang, James M Holaska

Rowan-Virtua School of Osteopathic Medicine Departmental Research

During metastasis, cancer cells traverse the vasculature by squeezing through very small gaps in the endothelium. Thus, nuclei in metastatic cancer cells must become more malleable to move through these gaps. Our lab showed invasive breast cancer cells have 50% less emerin protein resulting in smaller, misshapen nuclei, and higher metastasis rates than non-cancerous controls. Thus, emerin deficiency was predicted to cause increased nuclear compliance, cell migration, and metastasis. We tested this hypothesis by downregulating emerin in noninvasive MCF7 cells and found emerin knockdown causes smaller, dysmorphic nuclei, resulting in increased impeded cell migration. Emerin reduction in invasive breast cancer …


Developing A Comprehensive Genome-Scale Metabolic Model For The Arabidopsis Thaliana Root System, Lohani Esterhuizen Aug 2024

Developing A Comprehensive Genome-Scale Metabolic Model For The Arabidopsis Thaliana Root System, Lohani Esterhuizen

Department of Chemical and Biomolecular Engineering: Dissertations, Theses, and Student Research

Arabidopsis thaliana (Arabidopsis) is the most well-established model plant to date. Being the first plant to have its genome mapped, studies on Arabidopsis have provided insurmountable insights into the physiological and biochemical nature of plants. Methods that allow us to computationally study the metabolism of organisms include the use of genome-scale metabolic models (GEMs). Despite its popularity, no GEM currently maps the metabolic activity in the root system of Arabidopsis, which is the first organ to face and respond to stress conditions in the soil. This work aims to develop and implement a comprehensive GEM of the Arabidopsis root system …


Elucidating The Roles Of Septin Proteins In Thermotolerance And Cell Wall Integrity In Cryptococcus Neoformans, Stephani S. Martinez Barrera Aug 2024

Elucidating The Roles Of Septin Proteins In Thermotolerance And Cell Wall Integrity In Cryptococcus Neoformans, Stephani S. Martinez Barrera

All Dissertations

Cryptococcus neoformans is a globally distributed fungal pathogen responsible for causing cryptococcal meningitis in immunocompromised individuals. This pathogenic yeast must adapt to changes in temperature upon entering the human host. Septin proteins are conserved filament-forming GTPases that assemble as higher-order complexes at the cell cortex to support cytokinesis and morphogenesis in fungal and animal cells. In C. neoformans, four septin homologs (Cdc3, Cdc10, Cdc11, and Cdc12) assemble at the mother-bud neck, contributing to cytokinesis through poorly understood mechanisms. C. neoformans strains lacking the septins Cdc3 or Cdc12 are viable at 25°C, but fail to proliferate at 37°C, and are …


Role Of Sds-22/Pp1 Phosphatase In Polarizing The Germplasm Of Caenorhabditis Elegans Embryo, Aparna Nurni Ravi Jul 2024

Role Of Sds-22/Pp1 Phosphatase In Polarizing The Germplasm Of Caenorhabditis Elegans Embryo, Aparna Nurni Ravi

Dartmouth College Ph.D Dissertations

During asymmetric cell division, cell polarity and cell cycle are tightly coupled to ensure robust segregation of cell fate determinants and generation of cellular diversity. In the one-cell C. elegans embryo, multiple cell cycle kinases regulate cell polarization and posterior segregation of germline fate determinants (germplasm). For example, PLK-1 kinase inhibits the retention of its germplasm substrate POS-1 in the anterior, driving POS-1 segregation to the posterior (Han et al., 2018). Additionally, MBK-2 kinase disassembles P granules in the anterior through phosphorylation of the P granule scaffold MEG-3, helping to drive P granule segregation to the posterior (Wang et al., …


Functional And Structural Analysis Of The Neimann-Pick Disease Type C Pathway To Include Caveolin-1, Anthony Michael Seat Jul 2024

Functional And Structural Analysis Of The Neimann-Pick Disease Type C Pathway To Include Caveolin-1, Anthony Michael Seat

Chemistry and Chemical Biology ETDs

Human disease is often thought of as an all or nothing prospect, either one has the disease or one does not. This does not bear out in clinical or personal experiences, instead demonstrating that disease occurs within a spectrum ranging from presumed unaffected to demonstrably and detrimentally affected.Neimann-Pick disease is one example of this spectrum look into diseased states, with multiple named versions of a phenotypically similar disease. We focus on Neimann-Picktype C (NPC), which is the result of a disruption in the efflux of cholesterol and sphingolipids from the endocytic pathway. NPC demonstrates this concept of a spectrum of …


Interleukin 24 Induces Apoptosis Through Glycogen Synthase Kinase-3 Beta Inactivation In Prostate Cancer Cells, Sual J. Lopez, Moira Sauane Jul 2024

Interleukin 24 Induces Apoptosis Through Glycogen Synthase Kinase-3 Beta Inactivation In Prostate Cancer Cells, Sual J. Lopez, Moira Sauane

Theses and Dissertations

Interleukin 24 (IL-24) is a tumor-suppressing protein currently in clinical trials. IL-24 induces cancer-specific apoptosis by activating endoplasmic reticulum (ER) stress and mitochondria dysfunction. We have previously demonstrated that IL-24 leads to apoptosis in cancer cells by protein kinase A (PKA) activation in human breast cancer cells. To further understand the mechanism by which IL-24 induces apoptosis, I analyzed the role of glycogen synthase kinase-3 (GSK3), a highly conserved and normally active serine/threonine kinase in cancer cells and downstream target of PKA. The work reported here provides direct evidence that GSK3 was inhibited following IL-24 treatment in human prostate cancer …


Optimizing The Expression Of Polyethylene Terephtalate Hydrolase-Encoding Synthetic Gene In Escherichia Coli Arctic Express (De3), Jocelyn Nataniel, Maria Ulfah, Dini Achnafani, Niknik Nurhayati, Gabriela Christy Sabbathini, Sri Rezeki Wulandari, Abinawanto Abinawanto, Is Helianti Jun 2024

Optimizing The Expression Of Polyethylene Terephtalate Hydrolase-Encoding Synthetic Gene In Escherichia Coli Arctic Express (De3), Jocelyn Nataniel, Maria Ulfah, Dini Achnafani, Niknik Nurhayati, Gabriela Christy Sabbathini, Sri Rezeki Wulandari, Abinawanto Abinawanto, Is Helianti

Makara Journal of Science

The waste of polyethylene terephthalate (PET) plastic waste in Indonesia is a pressing concern due to its slow degradation and potential environmental damage. One promising solution is to utilize polyethylene terephthalate hydrolase from Ideonella sakaiensis (IsPETase), an enzyme that specifically degrades PET. However, inducing the expression of IsPETase synthetic gene in Escherichia coli BL21 (DE3) has been challenging because much of it remains insoluble. This study aimed to express IsPETase in E. coli Arctic Express (DE3) and optimize the conditions to enhance its production. First, pET22b(+)pelB-IsPETase was inserted into E. coli Arctic Express (DE3). The …


Rewiring The Sex-Determination Pathway During The Evolution Of Self-Fertility., Yongquan Shen, Shin-Yi Lin, Jonathan Harbin, Richa Amin, Allison Vassalotti, Joseph Romanowski, Emily Schmidt, Alexis Tierney, Ronald E Ellis Jun 2024

Rewiring The Sex-Determination Pathway During The Evolution Of Self-Fertility., Yongquan Shen, Shin-Yi Lin, Jonathan Harbin, Richa Amin, Allison Vassalotti, Joseph Romanowski, Emily Schmidt, Alexis Tierney, Ronald E Ellis

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Although evolution is driven by changes in how regulatory pathways control development, we know little about the molecular details underlying these transitions. The TRA-2 domain that mediates contact with TRA-1 is conserved in Caenorhabditis. By comparing the interaction of these proteins in two species, we identified a striking change in how sexual development is controlled. Identical mutations in this domain promote oogenesis in Caenorhabditis elegans but promote spermatogenesis in Caenorhabditis briggsae. Furthermore, the effects of these mutations involve the male-promoting gene fem-3 in C. elegans but are independent of fem-3 in C. briggsae. Finally, reciprocal mutations in these genes show …


Du Undergraduate Showcase Abstracts: Research, Scholarship, And Creative Works, August Alexander, Kevin Summers, E. Paige Lloyd, Alyssa Aragon, Lauren Wols, Erica Larson, Colton Arciniaga, Lily Baeza, Ellie Barnett-Cashman, Sidney Barbier, Maverick Bartholomew, Ryan Bell, Trevor Briggs, Amanda Brown, Cory Marchi, Maddy Pontius, Jennifer Gallagher, Claire Kwok, Channing Bullock, Alex Mccollister, Kim Gorgens, Daniela Chavez, Yamilet Espinoza Nuñez, Giovanni Valladares Giron, William Christensen, Olivia Kachulis, Daniel Cierasynski, Brandon Cohen, Spenser Dobbs, Lindsay Goolsby, Noah Craver, Nyah Cubbison, Liam Doherty, Nicole Doris, Yan Qin, Alexander Nguyen, Lily Harmon, Shubh Todi, Naichen Zhao, Noah Fagello, Stacia Fritz, Paola Gascot-Chinea, Alex Volkova, Janelyn Geronimo, Elsie Harrington, Shane Simmons, Clarice Hise, Laura Moreno Palmer, Henry Xu, Yesu Leela Pasupula, Emily Fisher, Zachary Hogan, Colin Kleckner, Alyssa Knaus, Erin Kubat, Sam Werkema, Katie Lamberton, Lilliya Larson, Allie Leary, Vanessa Leon-Gamez, James H. Gallagher, E. Dale Broder, Robin M. Tinghitella, Emma Loeber, Alina Mali, Ixchel Marquez, Lauren Mcgrath, Ella Matthews, Grace Naegelen, Audrey Ng, Megan Lucyshyn, Rachel Brough, Alexandra Norman, Joe Ontiveros Rodriguez, Ben Dossett, Ori Miller, Janamejay Sharma, Christopher Reardon, Vincent Pandey, Regan Parish, Ren Pratt, Alisha Pravasi, Sanchari Das, Cari Reichel, Emma Robson, Victoria Rockwell, Jayce Rumsey, Steven Said, Norah Schroder, Alaina Smith, Shannon Murphy, Shujan A. Sharafeldeen, Stanley M. Kanai, James T. Nichols, David E. Clouthier, Macalia R. Augustus, Daniel Silva Rios, Scott Simpson, Anna Sparling, Chase Spurbeck, Kimberly Chiew, Christine Stadnik-Poteroba, Jacqueline Stephenson, Evelyn Stovin, Mia Supan, Lauren Tapper, Will Thrush, Anna Vogt, Michaela Walheim, Jon Weber, Hunter Whitehouse, Kansas Wood, Hayley Sayre, Lydia Mccann, Maread Mclaughlin, Kelly Krumrie, Olivia Wuttke May 2024

Du Undergraduate Showcase Abstracts: Research, Scholarship, And Creative Works, August Alexander, Kevin Summers, E. Paige Lloyd, Alyssa Aragon, Lauren Wols, Erica Larson, Colton Arciniaga, Lily Baeza, Ellie Barnett-Cashman, Sidney Barbier, Maverick Bartholomew, Ryan Bell, Trevor Briggs, Amanda Brown, Cory Marchi, Maddy Pontius, Jennifer Gallagher, Claire Kwok, Channing Bullock, Alex Mccollister, Kim Gorgens, Daniela Chavez, Yamilet Espinoza Nuñez, Giovanni Valladares Giron, William Christensen, Olivia Kachulis, Daniel Cierasynski, Brandon Cohen, Spenser Dobbs, Lindsay Goolsby, Noah Craver, Nyah Cubbison, Liam Doherty, Nicole Doris, Yan Qin, Alexander Nguyen, Lily Harmon, Shubh Todi, Naichen Zhao, Noah Fagello, Stacia Fritz, Paola Gascot-Chinea, Alex Volkova, Janelyn Geronimo, Elsie Harrington, Shane Simmons, Clarice Hise, Laura Moreno Palmer, Henry Xu, Yesu Leela Pasupula, Emily Fisher, Zachary Hogan, Colin Kleckner, Alyssa Knaus, Erin Kubat, Sam Werkema, Katie Lamberton, Lilliya Larson, Allie Leary, Vanessa Leon-Gamez, James H. Gallagher, E. Dale Broder, Robin M. Tinghitella, Emma Loeber, Alina Mali, Ixchel Marquez, Lauren Mcgrath, Ella Matthews, Grace Naegelen, Audrey Ng, Megan Lucyshyn, Rachel Brough, Alexandra Norman, Joe Ontiveros Rodriguez, Ben Dossett, Ori Miller, Janamejay Sharma, Christopher Reardon, Vincent Pandey, Regan Parish, Ren Pratt, Alisha Pravasi, Sanchari Das, Cari Reichel, Emma Robson, Victoria Rockwell, Jayce Rumsey, Steven Said, Norah Schroder, Alaina Smith, Shannon Murphy, Shujan A. Sharafeldeen, Stanley M. Kanai, James T. Nichols, David E. Clouthier, Macalia R. Augustus, Daniel Silva Rios, Scott Simpson, Anna Sparling, Chase Spurbeck, Kimberly Chiew, Christine Stadnik-Poteroba, Jacqueline Stephenson, Evelyn Stovin, Mia Supan, Lauren Tapper, Will Thrush, Anna Vogt, Michaela Walheim, Jon Weber, Hunter Whitehouse, Kansas Wood, Hayley Sayre, Lydia Mccann, Maread Mclaughlin, Kelly Krumrie, Olivia Wuttke

DU Undergraduate Research Journal Archive

Abstracts from the DU Undergraduate Research Showcase.


Unveiling The Nexus Of Cellular Quality Control: Exploring The Interplay Between Ribosome-Associated Protein Quality Control And Mitochondrial Quality Control Pathways, Foozhan Tahmasebinia May 2024

Unveiling The Nexus Of Cellular Quality Control: Exploring The Interplay Between Ribosome-Associated Protein Quality Control And Mitochondrial Quality Control Pathways, Foozhan Tahmasebinia

Biological Sciences Theses and Dissertations

In eukaryotic cells, the intricate interplay between cellular quality control mechanisms is crucial for maintaining homeostasis and safeguarding the integrity of vital processes, spanning from macromolecule synthesis to the renewal of entire cellular organelles.

Disruption of these networks can lead to severe diseases such as metabolic disorders, underscoring the interconnected nature and feedback control mechanisms inherent in biological systems, including cellular quality control systems. This interconnectedness extends to the intricate communication between organelles, enabling coordinated functioning and adaptation to changing cellular conditions, particularly in response to stressors.

While the exact mechanisms governing these communications within cellular quality control systems remain …


Omani Camels From A Cultural And Genomics Perspective, Al Muatasim Al Zadjali May 2024

Omani Camels From A Cultural And Genomics Perspective, Al Muatasim Al Zadjali

Electronic Theses and Dissertations

The Dromedarian camel, Camelus dromedarius, is native to the Arabian Peninsula, including the Sultanate of Oman. These camels are used for food, milk, as well as show and racing competitions. Despite their economic and cultural importance research on camels in Oman is limited. The goal of this study was to examine their genomic variation, relationship with camels in other parts of the Arabian Peninsula, and to determine if selective breeding has led to the establishment of distinct breeds in Oman. Information was compiled from multiple sources to produce a comprehensive review on the breeding, management, economic and cultural use, …


Cis-Regulatory Mechanisms Through Stages Of Erythroid Regenration, Yichao Zhou May 2024

Cis-Regulatory Mechanisms Through Stages Of Erythroid Regenration, Yichao Zhou

Theses & Dissertations

Produced by steady state erythropoiesis, erythrocytes serve as vital regulators of metabolism and life by delivering oxygen to all the cells and tissues. Under acute anemia, steady state erythropoiesis is not sufficient to produce enough erythrocytes, leading to distinct mechanisms needed to regenerate large numbers of mature erythrocytes rapidly. Erythroid regeneration occurs in four stages: activation, expansion and differentiation, resolution, and post-resolution, according to the dynamics of erythrocyte numbers and progenitor activity. Erythroid regeneration throughout this timeline requires some critical extracellular cues, but the intrinsic molecular mechanisms needed to accelerate and decelerate the activity of erythroid progenitors in anemia and …


Characterizing The Role Of Pa5189 Of Pseudomonas Aeruginosa In Deletion And Overexpression Mutants, Seh Na Mellick May 2024

Characterizing The Role Of Pa5189 Of Pseudomonas Aeruginosa In Deletion And Overexpression Mutants, Seh Na Mellick

Theses/Capstones/Creative Projects

In the context of rising multidrug resistance in biofilm-forming pathogens like Pseudomonas aeruginosa, this study investigates the role of the understudied transcription factor PA5189 in antibiotic resistance and biofilm formation. PA5189 deletion and overexpression mutants were created in a parent P. aeruginosa strain using pEX18Tc-based recombinant suicide vectors, with genotypic verification of putative triparental conjugants achieved through restriction digestion and PCR. The study revealed that PA5189 overexpression significantly increases resistance to commonly used broad spectrum antibiotics such as ciprofloxacin and imipenem. Additionally, differential expression of PA5189 was found to notably affect biofilm formation, with variations contingent on the nutrient …


Trna Anticodon Cleavage By Target-Activated Crispr-Cas13a Effector, Ishita Jain, Matvey Kolesnik, Konstantin Kuznedelov, Leonid Minakhin, Natalia Morozova, Anna Shiriaeva, Alexandr Kirillov, Sofia Medvedeva, Alexei Livenskyi, Laura Kazieva, Kira S Makarova, Eugene V Koonin, Sergei Borukhov, Konstantin Severinov, Ekaterina Semenova Apr 2024

Trna Anticodon Cleavage By Target-Activated Crispr-Cas13a Effector, Ishita Jain, Matvey Kolesnik, Konstantin Kuznedelov, Leonid Minakhin, Natalia Morozova, Anna Shiriaeva, Alexandr Kirillov, Sofia Medvedeva, Alexei Livenskyi, Laura Kazieva, Kira S Makarova, Eugene V Koonin, Sergei Borukhov, Konstantin Severinov, Ekaterina Semenova

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Type VI CRISPR-Cas systems are among the few CRISPR varieties that target exclusively RNA. The CRISPR RNA–guided, sequence-specific binding of target RNAs, such as phage transcripts, activates the type VI effector, Cas13. Once activated, Cas13 causes collateral RNA cleavage, which induces bacterial cell dormancy, thus protecting the host population from the phage spread. We show here that the principal form of collateral RNA degradation elicited by Leptotrichia shahii Cas13a expressed in Escherichia coli cells is the cleavage of anticodons in a subset of transfer RNAs (tRNAs) with uridine-rich anticodons. This tRNA cleavage is accompanied by inhibition of protein synthesis, thus …


Tail-Tape-Fused Virion And Non-Virion Rna Polymerases Of A Thermophilic Virus With An Extremely Long Tail, Anastasiia Chaban, Leonid Minakhin, Ekaterina Goldobina, Brain Bae, Yue Hao, Sergei Borukhov, Leena Putzeys, Maarten Boon, Florian Kabinger, Rob Lavigne, Kira S Makarova, Eugene V Koonin, Satish K Nair, Shunsuke Tagami, Konstantin Severinov, Maria L Sokolova Jan 2024

Tail-Tape-Fused Virion And Non-Virion Rna Polymerases Of A Thermophilic Virus With An Extremely Long Tail, Anastasiia Chaban, Leonid Minakhin, Ekaterina Goldobina, Brain Bae, Yue Hao, Sergei Borukhov, Leena Putzeys, Maarten Boon, Florian Kabinger, Rob Lavigne, Kira S Makarova, Eugene V Koonin, Satish K Nair, Shunsuke Tagami, Konstantin Severinov, Maria L Sokolova

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Thermus thermophilus bacteriophage P23-45 encodes a giant 5,002-residue tail tape measure protein (TMP) that defines the length of its extraordinarily long tail. Here, we show that the N-terminal portion of P23-45 TMP is an unusual RNA polymerase (RNAP) homologous to cellular RNAPs. The TMP-fused virion RNAP transcribes pre-early phage genes, including a gene that encodes another, non-virion RNAP, that transcribes early and some middle phage genes. We report the crystal structures of both P23-45 RNAPs. The non-virion RNAP has a crab-claw-like architecture. By contrast, the virion RNAP adopts a unique flat structure without a clamp. Structure and sequence comparisons of …


Fused In Sarcoma Regulates Glutamate Signaling And Oxidative Stress Response, Chiong-Hee Wong, Abu Rahat, Howard C Chang Jan 2024

Fused In Sarcoma Regulates Glutamate Signaling And Oxidative Stress Response, Chiong-Hee Wong, Abu Rahat, Howard C Chang

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Mutations in fused in sarcoma (fust-1) are linked to ALS. However, how these ALS causative mutations alter physiological processes and lead to the onset of ALS remains largely unknown. By obtaining humanized fust-1 ALS mutations via CRISPR-CAS9, we generated a C. elegans ALS model. Homozygous fust-1 ALS mutant and fust-1 deletion animals are viable in C. elegans. This allows us to better characterize the molecular mechanisms of fust-1-dependent responses. We found FUST-1 plays a role in regulating superoxide dismutase, glutamate signaling, and oxidative stress. FUST-1 suppresses SOD-1 and VGLUT/EAT-4 in the nervous system. FUST-1 also regulates synaptic AMPA-type glutamate receptor …


Rps6kb1 Is A Critical Target For Overcoming Tumor Lineage Plasticity And Therapy Resistance, Saptadwipa Ganguly Jan 2024

Rps6kb1 Is A Critical Target For Overcoming Tumor Lineage Plasticity And Therapy Resistance, Saptadwipa Ganguly

Theses and Dissertations--Toxicology and Cancer Biology

Most tumors initially respond to treatment, yet refractory clones subsequently develop owing to resistance mechanisms which can be classified as intrinsic or extrinsic resistance. The intrinsic resistance is usually present prior to any treatment whereas the extrinsic resistance develops as a result of exposure to some kind of therapy. In order to target these “therapy resistant” tumor cells an unbiased screen of an FDA-approved drug library against cancer cells was performed. This was followed by synthesis of chemical analogs of the most effective drug.

The studies led to the identification of a derivative of the antihistamine drug ebastine, designated Super-ebastine …


An Rnai-Based Approach To Ips Calligraphus Management: A Promising Strategy For Forest Protection, Mary Wallace Jan 2024

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 …


Contributions Of The Replication Initiator Protein Dnaa To Physiology And Virulence Of The Lyme Disease Spirochete, Andrew Krusenstjerna Jan 2024

Contributions Of The Replication Initiator Protein Dnaa To Physiology And Virulence Of The Lyme Disease Spirochete, Andrew Krusenstjerna

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Borrelia burgdorferi, the etiological agent of Lyme disease, is the most prevalent vector-borne disease in the United States. The spirochetal population is naturally maintained by consistently cycling between Ixodid ticks and small vertebrates. To survive within these diverse niches, B. burgdorferi has evolved a unique physiology and regulatory network to sense and respond to environmental fluxes. Replication is a hallmark of the Lyme spirochete’s enzootic life cycle, specifically at the nymphal tick-to-vertebrate interface. The mechanisms and regulatory schema for the basic cellular processes in B. burgdorferi, or indeed any member of the phylum spirochaetota, are largely unknown. The central hypothesis …


Exploring 3d Genome Interaction And Epigenetic Regulation Via Swi/Snf Complex And Deep Learning Models, Ruoyun Wang Jan 2024

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 …


The Function Of Protein Glutamylation In Vision, Rawaa Aljammal Jan 2024

The Function Of Protein Glutamylation In Vision, Rawaa Aljammal

Graduate Theses, Dissertations, and Problem Reports (ETD)

Posttranslational glutamylation of protein has emerged as a novel candidate for cellular integrity. In a dynamic process, Tubulin Tyrosine Ligase Like proteins (TTLLs) introduce glutamate groups to their substrates, while Cytosolic Carboxypeptidases members (CCP1-CCP6) remove these glutamate groups. The outcome of this interplay is a wide range of substrates; each is glutamylated to a level crucial for its function.

Protein glutamylation is particularly abundant in neurons and in the axoneme of cilia and flagella. This distribution, along with the correlation between imbalanced glutamylation levels and compromised cellular functions, underscores the significance of protein glutamylation in maintaining cellular viability. However, the …


Structural And Functional Consequences Of Pde6 Prenylation In Rod And Cone Photoreceptors, Faezeh Moakedi Jan 2024

Structural And Functional Consequences Of Pde6 Prenylation In Rod And Cone Photoreceptors, Faezeh Moakedi

Graduate Theses, Dissertations, and Problem Reports (ETD)

Phosphodiesterase-6 (PDE6) serves as a pivotal component in the phototransduction pathways of both cone and rod photoreceptors. In cones, PDE6 consists of tetrameric subunits: inhibitory (γ') and catalytic (α'). The catalytic subunit, PDE6α', contains a C-terminal prenylation motif. Deletion of this motif is associated with achromatopsia (ACHM), a form of color blindness. The mechanisms underlying the disease and the roles of PDE6 lipidation in vision remain elusive. Meanwhile, rod PDE6 is composed of α and β catalytic subunits and γ inhibitory subunits, with alterations in the C-terminal "prenylation motif" of PDE6β linked to retinitis pigmentosa (RP) pathology. In this comprehensive …


The Evolution Of The Metazoan Circadian Molecular Mechanism And The Conservation Of Canonical Circadian Elements, Olivia Waldridge Jan 2024

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 …


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 Dec 2023

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 Dec 2023

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 …


Identification And Characterization Of Geotrichum Candidum Isolates From Peach With Reduced Sensitivity To Propiconazole, Sara Price Dec 2023

Identification And Characterization Of Geotrichum Candidum Isolates From Peach With Reduced Sensitivity To Propiconazole, Sara Price

All Theses

Geotrichum candidum Link (1809) is a yeast-like fungus that causes sour rot of stone fruits, including peach (Prunus persica). The disease caused damage between 2021 and 2023 to the peach crop kept in cold storage at a commercial farm in South Carolina despite preharvest and postharvest applications of fungicides. Isolates from 41 symptomatic fruit, from a South Carolina (SC) commercial packing house, as well as other isolates obtained from South Carolina were identified to be G. candidum based on species-specific PCR amplifications of the β tubulin gene. Commonly used postharvest fungicide fludioxonil had no effect on G. candidum mycelial growth …


Modeling Nonsegmented Negative-Strand Rna Virus (Nnsv) Transcription With Ejective Polymerase Collisions And Biased Diffusion, Felipe-Andres Piedra Sep 2023

Modeling Nonsegmented Negative-Strand Rna Virus (Nnsv) Transcription With Ejective Polymerase Collisions And Biased Diffusion, Felipe-Andres Piedra

Research Symposium

Background: The textbook model of NNSV transcription predicts a gene expression gradient. However, multiple studies show non-gradient gene expression patterns or data inconsistent with a simple gradient. Regarding the latter, several studies show a dramatic decrease in gene expression over the last two genes of the respiratory syncytial virus (RSV) genome (a highly studied NNSV). The textbook model cannot explain these phenomena.

Methods: Computational models of RSV and vesicular stomatitis virus (VSV – another highly studied NNSV) transcription were written in the Python programming language using the Scientific Python Development Environment. The model code is freely available on GitHub: …