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P53r245w Mutation Elicits Metastatic Phenotype In Pten Deficient Prostate Cancer, Ky Pham 2019 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

P53r245w Mutation Elicits Metastatic Phenotype In Pten Deficient Prostate Cancer, Ky Pham

Dissertations and Theses (Open Access)

Trp53 mutations are the most frequent genetic alterations in prostate cancer and are associated with more aggressive disease and worse overall survival. The majority of Trp53 mutations in prostate cancer are missense mutations, resulting in amino acid substitutions with profound effect. In addition to the loss of wild type function, missense mutations in Trp53 result in a gain-of-function (GOF) phenotype. This GOF phenotype confers biologic advantages to the tumor cells, enabling them to metastasize and invade distant organs. In this study, we generated mice carrying a conditional prostate-specific p53R245W mutant and Pten deletion to access the role of this common …


Sequence Analysis Of The Ren1 Genomic Region From The Grapevine ‘Kishmish Vatkana’, Dani Joseph 2019 Missouri State University

Sequence Analysis Of The Ren1 Genomic Region From The Grapevine ‘Kishmish Vatkana’, Dani Joseph

Graduate Theses/Dissertations

The REN1 region of the grapevine ‘Kishmish Vatkana’ was mapped as the locus that confers resistance to the economically important disease, grape powdery mildew. The purpose of this work was to extend the nucleotide sequence information of this region. By sequencing a heretofore unknown bacterial artificial chromosome clone, the sequence information of this region was extended by 46,890 nucleotides. Sequencing was performed using the third-generation sequencing method, named Oxford Nanopore Technology (ONT). In order to improve the accuracy of the sequence data, a modified ONT library preparation method was developed. ONT sequencing of a library prepared with the modified protocol …


Emergence Of Oxacillin Resistance In Stealth Methicillin-Resistant Staphylococcus Aureus Due To Meca Sequence Instability, Richard V. Goering, Erin A. Swartzendriber, Anne E. Obradovich, Isabella A. Tickler, Fred C. Tenover 2019 Creighton University

Emergence Of Oxacillin Resistance In Stealth Methicillin-Resistant Staphylococcus Aureus Due To Meca Sequence Instability, Richard V. Goering, Erin A. Swartzendriber, Anne E. Obradovich, Isabella A. Tickler, Fred C. Tenover

Biology Faculty Publications

Staphylococcus aureus strains that possess a mecA gene but are phenotypically susceptible to oxacillin and cefoxitin (OS-MRSA) have been recognized for over a decade and are a challenge for diagnostic laboratories. The mechanisms underlying the discrepancy vary from isolate to isolate. We characterized seven OS-MRSA clinical isolates of six different spa types from six different states by whole-genome sequencing to identify the nucleotide sequence changes leading to the OS-MRSA phenotype. The results demonstrated that oxacillin susceptibility was associated with mutations in regions of nucleotide repeats within mecA. Subinhibitory antibiotic exposure selected for secondary mecA mutations that restored oxacillin resistance. …


Mixing It Up: The Impact Of Episodic Introgression On The Evolution Of High-Latitude Mesocarnivores, Jocelyn P. Colella 2019 University of New Mexico

Mixing It Up: The Impact Of Episodic Introgression On The Evolution Of High-Latitude Mesocarnivores, Jocelyn P. Colella

Biology ETDs

At high latitudes, climatic oscillations have triggered repeated episodes of organismal divergence by geographically isolating populations. For terrestrial species, extended isolation in glacial refugia – ice-free regions that enable terrestrial species persistence through glacial maxima – is hypothesized to stimulate allopatric divergence. Alternatively, upon glacial recession, divergent populations expanded from independent glacial refugia and often contacted other diverging populations. In the absence of reproductive isolating mechanisms, this biogeographic process may trigger hybridization and ultimately, gene flow between divergent taxa. My dissertation research aims to understand how these episodic periods of isolation and contact have impacted the evolution of high latitude …


A Method For Improving The Accuracy And Efficiency Of Bacteriophage Genome Annotation, Philippos Tsourkas, Alicia Salisbury 2019 University of Nevada, Las Vegas

A Method For Improving The Accuracy And Efficiency Of Bacteriophage Genome Annotation, Philippos Tsourkas, Alicia Salisbury

Life Sciences Faculty Research

Bacteriophages are the most numerous entities on Earth. The number of sequenced phage genomes is approximately 8000 and increasing rapidly. Sequencing of a genome is followed by annotation, where genes, start codons, and functions are putatively identified. The mainstays of phage genome annotation are auto-annotation programs such as Glimmer and GeneMark. Due to the relatively small size of phage genomes, many groups choose to manually curate auto-annotation results to increase accuracy. An additional benefit of manual curation of auto-annotated phage genomes is that the process is amenable to be performed by students, and has been shown to improve student recruitment …


Characterization Of Human Dutpase, Shawna Marie Rotoli 2019 Rowan University

Characterization Of Human Dutpase, Shawna Marie Rotoli

Graduate School of Biomedical Sciences Theses and Dissertations

Deoxyuridine nucleotidyl transferase (dUTPase) is an enzyme found in all organisms that have thymine as a component of DNA. It catalyzes the hydrolysis of dUTP to dUMP and pyrophosphate thus precluding the buildup of dUTP pools as well as providing the substrate, dUMP, for the de novo synthesis of thymidylate. In Homo sapiens, there are four isoforms: mitochondrial (mDut), nuclear (nDut), variant 3 and variant 4. This work is largely focused on nDut. Using structural and MS analyses of recombinant dUTPase constructs, an intermolecular disulfide bridge between cysteine-3 of each nDut monomer was discovered. It was found that these two …


Development Of A Prolyl Endopeptidase Expression System In Lactobacillus Reuteri To Reduce The Clinical Manifestation Of Celiac Disease, Kara Lynn Jew 2019 California Polytechnic State University, San Luis Obispo

Development Of A Prolyl Endopeptidase Expression System In Lactobacillus Reuteri To Reduce The Clinical Manifestation Of Celiac Disease, Kara Lynn Jew

Master's Theses

Celiac Disease (CD) is an autoimmune disorder that emerges due to the ingestion of gluten, a protein found in a variety of common grains such as wheat, rye, and barley. Approximately 1 in 100 individuals in the US suffer from CD, making it the most commonly diagnosed gastrointestinal disorder (Ciclitira et. al., 2005). These proline-rich gluten peptides are resistant to proteolysis and accumulate in the duodenum of the small intestine. Once in the duodenum, these peptides illicit an autoimmune response resulting in villous atrophy. Current treatment for CD requires a rigorous adherence to a gluten-free diet. Nevertheless, gluten-containing grains are …


The Yeast Protein Mam33 Functions In The Assembly Of The Mitochondrial Ribosome, Gabrielle A Hillman, Michael F Henry 2019 Rowan University

The Yeast Protein Mam33 Functions In The Assembly Of The Mitochondrial Ribosome, Gabrielle A Hillman, Michael F Henry

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Mitochondrial ribosomes are functionally specialized for the synthesis of several essential inner membrane proteins of the respiratory chain. Although remarkable progress has been made toward understanding the structure of mitoribosomes, the pathways and factors that facilitate their biogenesis remain largely unknown. The long unstructured domains of unassembled ribosomal proteins are highly prone to misfolding and often require dedicated chaperones to prevent aggregation. To date, chaperones that ensure safe delivery to the assembling ribosome have not been identified in the mitochondrion. In this study, a respiratory synthetic lethality screen revealed a role for an evolutionarily conserved mitochondrial matrix protein called Mam33 …


The Effect Of Intracellular Zinc Levels In Escherichia Coli On Metallo-Β-Lactamase Activity, Jill Thompson 2019 Rowan University

The Effect Of Intracellular Zinc Levels In Escherichia Coli On Metallo-Β-Lactamase Activity, Jill Thompson

Graduate School of Biomedical Sciences Theses and Dissertations

Antibiotic resistance is a consequence of evolution via natural selection and poses a serious threat to the world's population. Escherichia coli, and other bacterial species, have acquired genes encoding Metallo-β-Lactamases (MBLs). MBLs are zinc-dependent enzymes that degrade most β-lactam antibiotics, and have emerged as important antibacterial resistance determinants in multidrug resistant pathogens. There are several different families of MBLs, and the major clinically relevant ones are Verona Integrated-encoded Metallo-β-Lactamases (VIMs), Imipenemases (IMPs), and New Delhi Metallo-β-Lactamases (NDMs). These enzymes confer high level resistance to penicillins, cephalosporins, and carbapenems, and are not inhibited by FDA-approved β-lactamase inhibitors. Variants of NDM have …


Protocol Measuring Horizontal Gene Transfer From Algae To Non-Photosynthetic Organisms, James Weifu Lee 2019 Old Dominion University

Protocol Measuring Horizontal Gene Transfer From Algae To Non-Photosynthetic Organisms, James Weifu Lee

Chemistry & Biochemistry Faculty Publications

Horizontal gene transfer (HGT) is a natural process for an organism to transfer genetic material to another organism that is a completely different species, for example, from a blue-green alga to a non-photosynthetic bacterium. The phenomenon of HGT is not only of an interest to the science of molecular genetics and biology, but also to the biosafety issue of genetic engineering. The novel protocol reported here for the first time teaches how to measure HGT from a genetically engineered (GE) blue-green alga (gene donor) to wild-type E. coli (recipient). This novel protocol can be used to measure HGT frequency for …


Hippo Signaling In Cancer: Lessons From Drosophila Models, Kirti Snigdha, Karishma Sanjay Gangwani, Gauri Vijay Lapalikar, Amit Singh, Madhuri Kango-Singh 2019 University of Dayton

Hippo Signaling In Cancer: Lessons From Drosophila Models, Kirti Snigdha, Karishma Sanjay Gangwani, Gauri Vijay Lapalikar, Amit Singh, Madhuri Kango-Singh

Biology Faculty Publications

Hippo pathway was initially identified through genetic screens for genes regulating organ size in fruitflies. Recent studies have highlighted the role of Hippo signaling as a key regulator of homeostasis, and in tumorigenesis. Hippo pathway is comprised of genes that act as tumor suppressor genes like hippo (hpo) and warts (wts), and oncogenes like yorkie (yki). YAP and TAZ are two related mammalian homologs of Drosophila Yki that act as effectors of the Hippo pathway. Hippo signaling deficiency can cause YAP- or TAZ-dependent oncogene addiction for cancer cells. YAP and TAZ are often activated …


Dietary Restriction Enhances Circadian Amplitude And Delays Visual Decline By A Clock-Driven Increase In Phototransduction, Geoff Meyerhof 2019 Dominican University of California

Dietary Restriction Enhances Circadian Amplitude And Delays Visual Decline By A Clock-Driven Increase In Phototransduction, Geoff Meyerhof

Natural Sciences and Mathematics | Biological Sciences Master's Theses

Aging is accompanied by a progressive loss of circadian rhythms. Lifespan-extending dietary paradigms such as dietary restriction (DR) enhance circadian amplitude and appear to extend lifespan in a clock-dependent fashion. However, the mechanisms by which DR amplifies circadian rhythms and why circadian rhythms decline with age have yet to be fully elucidated. Here we find that DR amplifies circadian amplitude by enhancing light sensitivity in the eye. We performed a circadian mRNA microarray in flies (Drosophila melanogaster) reared on DR or a high nutrient diet and found that DR increases the number of circadian transcripts and selectively amplifies the …


Frogs Hiding In Plain Sight: Phylogenetic Systematics Of Myanmar’S Occidozyga Species Complex, And The Identification Of A Novel Species, Allison Bogisich 2019 University of San Francisco

Frogs Hiding In Plain Sight: Phylogenetic Systematics Of Myanmar’S Occidozyga Species Complex, And The Identification Of A Novel Species, Allison Bogisich

Master's Theses

Different species can be difficult to distinguish from one another when they are morphologically similar. Such cryptic species are the reason many anuran species go undetected. For this study, the taxonomic identity of the Occidozyga complex across Myanmar was investigated. An integrated approach was used combining molecular, morphological and phylogeographic data to better assess its taxonomy. Results indicate the presence of three new candidate species within Occidozyga, and three evolutionarily significant unit (ESU) lineages. Two mitochondrial gene fragments (16S, COI) and one nuclear gene fragment (Rhodopsin) were examined from DNA isolated from forty-seven preserved specimens from the California Academy …


Clinical Utility Of Exon Deletion/Duplication Microarray Testing - A Children’S Mercy Kansas City Two-Year Experience, Binu Porath 2019 Children's Mercy Kansas City

Clinical Utility Of Exon Deletion/Duplication Microarray Testing - A Children’S Mercy Kansas City Two-Year Experience, Binu Porath

Research Days

No abstract provided.


A Discrepancy Between The Human Reference Genome (Grch37) And Transcriptome (Refseq) Results In The Incorrect Annotation Of A Clinically-Relevant Sequence Variant In Recql4, Lisa A. Lansdon 2019 Children's Mercy Kansas City

A Discrepancy Between The Human Reference Genome (Grch37) And Transcriptome (Refseq) Results In The Incorrect Annotation Of A Clinically-Relevant Sequence Variant In Recql4, Lisa A. Lansdon

Research Days

No abstract provided.


Warming Up: Climate Change Related Shifts Of Mycorrhizal Fungal Communities In High Latitude Ecosystems, Megan Rae DeVan 2019 University of New Mexico

Warming Up: Climate Change Related Shifts Of Mycorrhizal Fungal Communities In High Latitude Ecosystems, Megan Rae Devan

Biology ETDs

This dissertation examines how climate change affects mycorrhizal fungal communities in boreal and arctic ecosystems. In chapter one, I revealed that increases in fire severity and related increases in deciduous tree dominance result in greater Ascomycota relative abundance (RA) and subsequent declines in Basidiomycota RA. In chapter two I analyzed the effects of post-fire mycorrhizal fungal communites on host growth. There were trends at the fungal genus level that were largely reflected at the guild level across all hosts; however, there were some fungal genera that had the opposite effect on different host species. In chapter three, I found host …


Maintenance Of Genetic And Epigenetic Stability During Dna Double-Strand Break Repair And Dna Replication, Nathaniel Edward Wiest 2019 University of New Mexico

Maintenance Of Genetic And Epigenetic Stability During Dna Double-Strand Break Repair And Dna Replication, Nathaniel Edward Wiest

Biomedical Sciences ETDs

Eukaryotic genomes are assembled into a complex of DNA and proteins known as chromatin. The packaging of DNA into chromatin is the foundational strategy that cells use to both compress genomic DNA into nuclei and regulate access to its contents. The basic repeating subunit of chromatin is the nucleosome, composed of an octamer of two copies of each of the core histone proteins H2A, H2B, H3, and H4 around which 146 bp of DNA are tightly wrapped. While the compaction of genomes into chromatin offers cells significant advantages, it also presents serious challenges to fundamental processes that maintain genome integrity, …


Fungi In A Hot, Dry, Changing World, Miriam I. Hutchinson 2019 University of New Mexico

Fungi In A Hot, Dry, Changing World, Miriam I. Hutchinson

Biology ETDs

My doctoral work focused on understanding the reciprocal relationship between fungi and their environment, namely how fungi respond to environmental flux, as well as how fungi can modify and structure their habitats, especially in the context of climate change. As such, I aimed my research on fungi with distinct adaptations to their environmental niches: endophytic fungi that inhabit plant tissue and thermophilic fungi that are capable of growing at the upper temperature limit for eukaryotic life. My research consisted of three studies. First, I investigated the thermophilic species Myceliophthora heterothallica to demonstrate its use as a model organism for efficient …


Analyzing The Effect Of Apoptotic Mutations On The State Of The Nascent-Polypeptide Associated Complex In Caenorhabditis Elegans, Monica Gerber 2019 James Madison University

Analyzing The Effect Of Apoptotic Mutations On The State Of The Nascent-Polypeptide Associated Complex In Caenorhabditis Elegans, Monica Gerber

Senior Honors Projects, 2010-2019

Cells experiencing misfolded protein stress can become debilitated and die, contributing to the onset of disease. The nascent polypeptide-associated complex (NAC) is a heterodimeric translational chaperone that protects against misfolded protein stress by mediating proper protein folding and localization during translation. Depletion of this complex results in misfolded protein accumulation in the endoplasmic reticulum (ER). To determine the importance of the NAC to proteostasis, we have previously depleted the complex in C.elegans via RNA interference and observed numerous dose-dependent effects, including apoptosis of neuronal cells and changes in gene expression of hypodermal cells. While we have observed these cell-specific responses …


Yeast Mitochondrial Protein Pet111p Binds Directly To Two Distinct Targets In Cox2 Mrna, Suggesting A Mechanism Of Translational Activation, Julia L Jones, Katharina B Hofmann, Andrew T Cowan, Dmitry Temiakov, Patrick Cramer, Michael Anikin 2019 Rowan University

Yeast Mitochondrial Protein Pet111p Binds Directly To Two Distinct Targets In Cox2 Mrna, Suggesting A Mechanism Of Translational Activation, Julia L Jones, Katharina B Hofmann, Andrew T Cowan, Dmitry Temiakov, Patrick Cramer, Michael Anikin

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The genes in mitochondrial DNA code for essential subunits of the respiratory chain complexes. In yeast, expression of mitochondrial genes is controlled by a group of gene-specific translational activators encoded in the nucleus. These factors appear to be part of a regulatory system that enables concerted expression of the necessary genes from both nuclear and mitochondrial genomes to produce functional respiratory complexes. Many of the translational activators are believed to act on the 5'-untranslated regions of target mRNAs, but the molecular mechanisms involved in this regulation remain obscure. In this study, we used a combination of in vivo and in …


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