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Sequence Properties Of An Intramolecular Interaction That Inhibits P53 Dna Binding, Emily Gregory, Gary W. Daughdrill 2022 University of South Florida

Sequence Properties Of An Intramolecular Interaction That Inhibits P53 Dna Binding, Emily Gregory, Gary W. Daughdrill

Molecular Biosciences Faculty Publications

An intramolecular interaction between the p53 transactivation and DNA binding domains inhibits DNA binding. To study this autoinhibition, we used a fragment of p53, referred to as ND WT, containing the N-terminal transactivation domains (TAD1 and TAD2), a proline rich region (PRR), and the DNA binding domain (DBD). We mutated acidic, nonpolar, and aromatic amino acids in TAD2 to disrupt the interaction with DBD and measured the effects on DNA binding affinity at different ionic strengths using fluorescence anisotropy. We observed a large increase in DNA binding affinity for the mutants consistent with reduced autoinhibition. The ΔΔG between DBD and …


Identifying Adaptor Proteins For Selective Mrna Export In S. Cerevisiae, Chloe Baker, Rebecca Adams 2022 Belmont University

Identifying Adaptor Proteins For Selective Mrna Export In S. Cerevisiae, Chloe Baker, Rebecca Adams

Science University Research Symposium (SURS)

The export of mature mRNA from the nucleus of the cell to the cytoplasm is crucial for a cell’s survival, as this process is necessary to produce proteins encoded by these transcripts. In S. cerevisiae (yeast) cells, a protein known as Mex67 must bind to the mRNA while it’s in the nucleus so it can cross through the nuclear pore complex (NPC). Mex67 cannot bind to the mRNA directly, instead it needs to be accompanied by adaptor proteins to aid it in getting across the NPC. Stress conditions such as heat shock interferes with the function of these adaptor …


Adenoviral-Vectored Centralized Consensus Hemagglutinin Vaccine Provides Broad Protection Against H2 Influenza A Virus, Erika M. Petro-Turnquist, Brianna L. Bullard, Matthew J. Pekarek, Eric A. Weaver 2022 University of Nebraska-Lincoln

Adenoviral-Vectored Centralized Consensus Hemagglutinin Vaccine Provides Broad Protection Against H2 Influenza A Virus, Erika M. Petro-Turnquist, Brianna L. Bullard, Matthew J. Pekarek, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Several influenza pandemics have occurred in the past century, one of which emerged in 1957 from a zoonotic transmission of H2N2 from an avian reservoir into humans. This pandemic caused 2–4 million deaths and circulated until 1968. Since the disappearance of H2N2 from human populations, there has been waning immunity against H2, and this subtype is not currently incorporated into seasonal vaccines. However, H2 influenza remains a pandemic threat due to consistent circulation in avian reservoirs. Here, we describe a method of pandemic preparedness by creating an adenoviral-vectored centralized consensus vaccine design against human H2 influenza. We also assessed the …


Analysis Of Hematocrit Levels In Walleye Sander Vitreus From Similar Waterbodies, Alyssa Hauser 2022 Bemidji State University

Analysis Of Hematocrit Levels In Walleye Sander Vitreus From Similar Waterbodies, Alyssa Hauser

Journal of Earth and Life Science

Walleye Sander vitreus are a popular fish among anglers and hold a prominent place in Minnesotan’s identity as their state fish. Because of this, multiple management practices are used to ensure the continued health of their populations within Minnesota waters. In this study, the process of analyzing hematocrit levels was used to determine if the analysis of hematological parameters could be a useful tool in detecting differences in population health. To evaluate this, blood samples were acquired from age-0 and age-1 fish from two similar lakes and run through a hematocrit centrifuge to separate platelets from plasma to read the …


A Novel Drug To Induce Apoptosis In Advanced Prostate Cancer Cells, Parshva A. Sanghvi 2022 University of Central Florida

A Novel Drug To Induce Apoptosis In Advanced Prostate Cancer Cells, Parshva A. Sanghvi

Honors Undergraduate Theses

Prostate cancer is one of the leading causes of death for men in America as approximately 1 in 41 men will have prostate cancer. In this research, we focus on enzalutamide-resistant prostate cancer cells as cell resistance to enzalutamide is a prevalent obstacle in treating prostate cancer. We tested a novel compound library at different doses and observed each compound's efficacy in inducing apoptosis in enzalutamide-resistant cells. Furthermore, we analyzed the mechanism by which apoptosis was induced in compounds that showed a high efficacy at lower doses. Overall, we found that Darapladib shows promising results in treating cells that have …


The Effect Of Ethanol On Cellular Movements And Development In C. Elegans, Caitlin N. O'Connor 2022 West Chester University

The Effect Of Ethanol On Cellular Movements And Development In C. Elegans, Caitlin N. O'Connor

West Chester University Master’s Theses

Neural tube development, which gives rise to the central nervous system, is vital to embryonic development. Neural tube defects, like spina bifida, are serious and common congenital defects which can result in life-long medical complications. Folic acid has been used as a preventative measure for neural tube defects and has appeared to decrease the occurrences of neural tube defects. However, the mechanism behind folic acid’s role in neural tube development is unclear. Furthermore, some evidence suggests that ethanol decreases the levels of folates and folate coenzymes in the fetal brain and downregulates folic acid metabolism genes. To better understand the …


Deciphering The Role And Clinical Application Of The Fgfr4-Klb-Fgf19 Axis In Colorectal Neoplastic Progression, Michael Rohr 2022 University of Central Florida

Deciphering The Role And Clinical Application Of The Fgfr4-Klb-Fgf19 Axis In Colorectal Neoplastic Progression, Michael Rohr

Electronic Theses and Dissertations, 2020-2023

Colorectal cancer (CRC) is the third most common and third deadliest cancer worldwide with rising incidence rates attributed to environmental risk factors like diet. Investigating how these factors impact carcinogenesis requires an understanding of how transcriptional events evolve with respect to neoplastic progression. We employed meta-transcriptomics and latent trajectory modeling to establish a compendium of profiled healthy, adenoma, and CRC samples scored by their position along a pseudotemporal axis. By interpolating a continuous scale from cross-sectional data, dynamic processes occurring throughout disease progression can be analyzed more accurately. For example, smaller pseudotimes represented pre-malignant dysplasia and was characterized by cellular …


In Vivo Metabolic Analysis Of The Anticancer Effects Of Plasma-Activated Saline In Three Tumor Animal Models, Miao Qi, Dehui Xu, Shuai Wang, Bing Li, Sansan Peng, Qiaosong Li, Hao Zhang, Runze Fan, Hai-Lan Chen, Michael G. Kong 2022 Old Dominion University

In Vivo Metabolic Analysis Of The Anticancer Effects Of Plasma-Activated Saline In Three Tumor Animal Models, Miao Qi, Dehui Xu, Shuai Wang, Bing Li, Sansan Peng, Qiaosong Li, Hao Zhang, Runze Fan, Hai-Lan Chen, Michael G. Kong

Bioelectrics Publications

In recent years, the emerging technology of cold atmospheric pressure plasma (CAP) has grown rapidly along with the many medical applications of cold plasma (e.g., cancer, skin disease, tissue repair, etc.). Plasma-activated liquids (e.g., culture media, water, or normal saline, previously exposed to plasma) are being studied as cancer treatments, and due to their advantages, many researchers prefer plasma-activated liquids as an alternative to CAP in the treatment of cancer. In this study, we showed that plasma-activated-saline (PAS) treatment significantly inhibited tumor growth, as compared with saline, in melanoma, and a low-pH environment had little effect on tumor growth in …


Modeling Jadera Haematoloma’S Phenotypic Variation In The Context Of Its Developmental Plasticity, Michael C. Yorsz 2022 Colby College

Modeling Jadera Haematoloma’S Phenotypic Variation In The Context Of Its Developmental Plasticity, Michael C. Yorsz

Honors Theses

Phenotypic plasticity is the ability of an organism to integrate information from environmental cues to inform the development of its phenotype and remains understudied in biology. Models of plasticity are needed because evolution in the presence of plasticity is poorly understood. Jadera haematoloma, a hemimetabolous true bug, is an excellent animal model of plasticity, exhibiting a non-linear plastic response to juvenile nutrition that biases adult development into groups with differences in flight capability, wing shape, and fecundity. However, there is a lack of literature consensus regarding the range of developmental outcomes in the species. Some publications report the presence …


Nutrient Scarcity And Cellular Cooperation In A Clonal Hydroid, Weam S. El Rahmany 2022 Northern Illinois University

Nutrient Scarcity And Cellular Cooperation In A Clonal Hydroid, Weam S. El Rahmany

Graduate Research Theses & Dissertations

Biological complexity forms when lower-level units (e.g., genes, cells, organisms) cooperatively band together. This complexity may be exemplified by multicellularity, the cooperation between the cells of the same species, or symbiosis, cooperation between the cells of different species. This cooperation is under continual threat, as defection, the opposite of cooperation, is favored by default by lower-level units (i.e., cells). Animal cancers may be the most well-known phenomena that exemplify the concept of cellular defection. Cancer cells have been shown to feature morphological and metabolic traits, developed through differential gene expression or mutations, that favor their growth at the cost of …


Xrcc4 And Mre11 Roles And Transcriptional Response To Repair Of Talen-Induced Double-Strand Dna Breaks, Ronald Benjamin, Atoshi Banerjee, Xiaogang Wu, Corey Geurink, Lindsay Buczek, Danielle Eames, Sara G. Trimidal, Janice M. Pluth, Martin R. Schiller 2022 University of Nevada, Las Vegas

Xrcc4 And Mre11 Roles And Transcriptional Response To Repair Of Talen-Induced Double-Strand Dna Breaks, Ronald Benjamin, Atoshi Banerjee, Xiaogang Wu, Corey Geurink, Lindsay Buczek, Danielle Eames, Sara G. Trimidal, Janice M. Pluth, Martin R. Schiller

Health Physics and Diagnostic Sciences Faculty Research

Double-strand breaks (DSB) are one of the most lethal forms of DNA damage that, if left unrepaired, can lead to genomic instability, cellular transformation, and cell death. In this work, we examined how repair of transcription activator-like effector nuclease (TALEN)-induced DNA damage was altered when knocking out, or inhibiting a function of, two DNA repair proteins, XRCC4 and MRE11, respectively. We developed a fluorescent reporter assay that uses TALENs to introduce DSB and detected repair by the presence of GFP fluorescence. We observed repair of TALEN-induced breaks in the XRCC4 knockout cells treated with mirin (a pharmacological inhibitor of MRE11 …


Characterizing The Lir Domain Of Abin1 And Identifying Its Role As A Regulator Of Mitophagy, Andrew Rhiner 2022 South Dakota State University

Characterizing The Lir Domain Of Abin1 And Identifying Its Role As A Regulator Of Mitophagy, Andrew Rhiner

Electronic Theses and Dissertations

A20 Inhibitor of NF-κB (ABIN1/TNIP1) is a known regulator of TNFα signaling induced cell death and inflammation. The regulatory activity has been attributed to ABIN1’s recruitment of the ubiquitin editing enzyme TNF-α-induced protein 3 (TNFAIP3/A20) to Receptor-interacting serine/threonine-protein kinase 1 (RIPK1). The regulation of RIPK1 by ABIN1 and A20 relies on a third player, linear ubiquitin chain assembly complex (LUBAC), which is involved in the recruitment of ABIN1 to RIPK1. Loss of LUBAC or ABIN1 is embryonic lethal, but loss of A20 is not embryonic lethal. The embryonic lethality due to loss of ABIN1, paired with the lack of lethality …


Salivary Gland Stromal Heterogeneity And Epithelial Controls, Nicholas L. Moskwa 2022 University at Albany, State University of New York

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 …


Mechanisms Underlying Pre- And Postnatal Development Of The Mouse Vomeronasal Organ, Raghu Ram Katreddi 2022 University at Albany, State University of New York

Mechanisms Underlying Pre- And Postnatal Development Of The Mouse Vomeronasal Organ, Raghu Ram Katreddi

Legacy Theses & Dissertations (2009 - 2024)

The Vomeronasal organ (VNO) is a specialized olfactory sensory organ located in the ventral region of the nasal cavity in rodents. The vomeronasal epithelium (VNE) of rodents is composed of 2 major types of vomeronasal sensory neurons (VSNs): 1) VSNs distributed in the apical VNE regions that express vomeronasal type-1 receptors (V1Rs) and the G protein subunit Gi2, and 2) VSNs in the basal territories of the VNE that express vomeronasal type-2 receptors (V2Rs) and the G subunit Go. Besides these two neuronal types, VNE also accommodate a third non-neuronal cell type called Sustentacular cells that lie anatomically above apical …


Genetic Regulation Within Cellular Stress Response Pathways, Jhos M. Dufflart 2022 University at Albany, State University of New York

Genetic Regulation Within Cellular Stress Response Pathways, Jhos M. Dufflart

Legacy Theses & Dissertations (2009 - 2024)

Cellular stress is something that a cell deals with on a regular basis. Fortunately, there are several different mechanisms that are set in place in order to deal with them. Depending on the stress present in the cell there will be different stress response pathways that are activated in order to mitigate the stress or initiate cellular death mechanisms. Transcription factors (TFs) are key components within these pathways, and this will be the focus of this thesis. TFs within mammalian stress response pathways are tasked with the essential regulation of multiple genes within these pathways and are oftentimes linked with …


Exploring The Roles Of Stress, Codon Usage, And Rna Modifications In Myotonic Dystrophy Type 1, Afrooz Golestanian 2022 University at Albany, State University of New York

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 …


Elucidating The Role Of Polycomb Repressive Complex 2 In Lung Stem Cell Fate And Lung Disease, Aria Byrd 2022 University of Kentucky

Elucidating The Role Of Polycomb Repressive Complex 2 In Lung Stem Cell Fate And Lung Disease, Aria Byrd

Theses and Dissertations--Toxicology and Cancer Biology

The average human lungs take ~22,000 breaths and inhale ~2,000 gallons of air each day. This organ is the primary conduit for the transfer of oxygen to the internal organs, making it crucial for the sustainment of life. Consequently, mechanical malfunction of the lungs and/or pollution of inhaled air negatively impact internal organ function and ultimately put survival in jeopardy. Epigenetics, by nature, is a plastic phenomenon in which environmental stimuli influence short term, long term, and generational gene expression patterns. Chronic exposure of harmful stimuli to the lung epithelium has also been shown to alter epigenetic pathways, engender aberrant …


Sex Dimorphism In Hematopoiesis And Bone Marrow Niche, xiaojing cui 2022 University of Kentucky

Sex Dimorphism In Hematopoiesis And Bone Marrow Niche, Xiaojing Cui

Theses and Dissertations--Toxicology and Cancer Biology

Hematopoietic stem cells (HSC), which are a rare population of cells existing in human circulating blood and bone marrow, can form the whole-blood system by their self-renewal capacity and differentiation ability. Sex dimorphism can be found in hematopoietic stem and progenitor cells, and in the development of hematopoietic lineages. Also, males are at higher risk and have a worse prognosis for most hematologic malignancies than females. Under normal conditions, the number of circulating progenitor cells in women is lower than in men. Furthermore, female mice have a higher rate of HSC division than male mice. A dramatic gender difference exists …


Exosomal-Long Non-Coding Rnas Journey In Colorectal Cancer: Evil And Goodness Faces Of Key Players, Nehal I. Rizk, Ahmed I. Abulsoud, Mohamed M. Kamal, Dina H. Kassem, Nadia M. Hamdy 2022 Heliopolis University

Exosomal-Long Non-Coding Rnas Journey In Colorectal Cancer: Evil And Goodness Faces Of Key Players, Nehal I. Rizk, Ahmed I. Abulsoud, Mohamed M. Kamal, Dina H. Kassem, Nadia M. Hamdy

Pharmacy

Exosomes are nano-vesicles (NVs) secreted by cells and take part in cell-cell communications. Lately, these exosomes were proved to have dual faces in cancer. Actually, they can contribute to carcinogenesis through epithelial-mesenchymal transition (EMT), angiogenesis, metastasis and tumor microenvironment (TME) of various cancers, including colorectal cancer (CRC). On the other hand, they can be potential targets for cancer treatment. CRC is one of the most frequent tumors worldwide, with incidence rates rising in the recent decades. In its early stage, CRC is asymptomatic with poor treatment outcomes. Therefore, finding a non-invasive, early diagnostic biomarker tool and/or suitable defender to combat …


Expanding Mouse-Adapted Yamagata-Like Influenza B Viruses In Eggs Enhances In Vivo Lethality In Balb/C Mice, Matthew J. Pekarek, Erika M. Petro-Turnquist, Adam Rubrum, Richard J. Webby, Eric A. Weaver 2022 University of Nebraska-Lincoln

Expanding Mouse-Adapted Yamagata-Like Influenza B Viruses In Eggs Enhances In Vivo Lethality In Balb/C Mice, Matthew J. Pekarek, Erika M. Petro-Turnquist, Adam Rubrum, Richard J. Webby, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Despite the yearly global impact of influenza B viruses (IBVs), limited host range has been a hurdle to developing a readily accessible small animal disease model for vaccine studies. Mouseadapting IBV can produce highly pathogenic viruses through serial lung passaging in mice. Previous studies have highlighted amino acid changes throughout the viral genome correlating with increased pathogenicity, but no consensus mutations have been determined. We aimed to show that growth system can play a role in mouse-adapted IBV lethality. Two Yamagata-lineage IBVs were serially passaged 10 times in mouse lungs before expansion in embryonated eggs or Madin–Darby canine kidney cells …


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