Molecular genetics Commons^™

Delayed Thrombus Resolution And Fibroproliferative Vascular Wound Healing From Deficiency Of Type Iii Collagen: A Paradoxical Mechanism For Tissue Fragility, Amy J. Reid

UT GSBS Dissertations and Theses (Open Access)

Vascular Ehlers-Danlos syndrome is a heritable disease of connective tissue caused by mutations in COL3A1, conferring a tissue deficiency of type III collagen. Cutaneous wounds heal poorly in these patients, and they are susceptible to spontaneous and catastrophic rupture of expansible hollow organs like the gut, uterus, and medium-sized to large arteries, which leads to premature death. Although the predisposition for organ rupture is often attributed to inherent tissue fragility, investigation of arteries from a haploinsufficient Col3a1 mouse model (Col3a1^+/-) demonstrates that mutant arteries withstand even supraphysiologic pressures comparably to wild-type vessels. We hypothesize that injury that elicits occlusive thrombi ...

Cellular Adaptation Of Macrophages To Anthrax Lethal Toxin-Induced Pyroptosis Via Epigenetic Mechanisms, Chae Young Han

University of Western Ontario - Electronic Thesis and Dissertation Repository

Cellular adaptation to microbial stresses has been demonstrated in several cell types. Macrophages (MФ) are sentinel immune cells fending off invading microbes. Anthrax lethal toxin (LeTx) is a key virulence factor released by Bacillus anthracis that causes rapid cell death, pyroptosis. A small number of RAW246.7 macrophages (~4%) exposed to a non-lethal dose of LeTx become resistant to LeTx-induced pyroptosis for ~ 4 weeks, termed “toxin-induced resistance (TIR)”. Here, I showed that high levels of DNA methyl transferase1 (DNMT1) expression were maintained although global genomic methylation levels were not high in TIR. TIR cells treated with the DNMT inhibitor 5-azacitidine ...

Contributions Of Apolipoprotein E And Environmental Factors In Alzheimer’S Disease, Kelly C. Mcmullen

Senior Honors Papers

Alzheimer’s disease (AD) is a debilitating neurodegenerative disorder, which currently affects nearly 5.5 million people in the United States alone. Clinical features often exhibited in AD include memory loss, unusual behavior, personality changes, and impaired cognitive function. The primary molecular hallmarks of AD include deposits of senile plaques and neurofibrillary tangles in brain tissue. A myriad of risk factors are associated with the disease, but this review will focus on Apolipoprotein E polymorphisms and certain environmental factors. Understanding the role of Apolipoprotein E in AD pathology may aid in the development of certain drug therapies and possible cures ...

A Compendium Of Caenorhabditis Elegans Rna Binding Proteins Predicts Extensive Regulation At Multiple Levels, Alex M. Tamburino, Sean P. Ryder, Albertha J. M. Walhout

Program in Systems Biology Publications and Presentations

Gene expression is regulated at multiple levels, including transcription and translation, as well as mRNA and protein stability. Although systems-level functions of transcription factors and microRNAs are rapidly being characterized, few studies have focused on the posttranscriptional gene regulation by RNA binding proteins (RBPs). RBPs are important to many aspects of gene regulation. Thus, it is essential to know which genes encode RBPs, which RBPs regulate which gene(s), and how RBP genes are themselves regulated. Here we provide a comprehensive compendium of RBPs from the nematode Caenorhabditis elegans (wRBP1.0). We predict that as many as 887 (4.4 ...

Epigenetics Of Stress Adaptation In Arabidopsis: The Case Of Histone Modifications, Behnaz Najafi Majdabadi Farahani

University of Western Ontario - Electronic Thesis and Dissertation Repository

Changes in the epigenetic status of plants, which contribute to changes in gene expression, in response to abiotic stress are well documented. However, their stability and transmission to subsequent generations, and their incorporation into plant stress adaptation are still a matter for debate. Using chromatin immuno-precipitation and Next Generation Sequencing (ChIP-seq), we compared genome wide enrichment of two histone marks, H3K9ac and H3K4me2, in the progeny of salt stressed and control Arabidopsis plants. Data showed less enrichment of the H3K9ac in the chromatin of the progeny of salt stressed plants, but no changes were detected in the enrichment of the ...

Characterization Of Genes And Pathways Controlling Biofilm Formation In Saccharomyces Cerevisiae, Neha Sarode

Doctoral Dissertations

Biofilms are a mode of growth where aggregated cells adhere to a foreign surface and grow as a complex community. Biofilms have found wide utility in commercial industries, however infections caused by biofilms in clinical settings are a major cause of concern. Understanding molecular details of biofilm formation could help in exploitation or elimination efforts.

We utilize Saccharomyces cerevisiae as a model system to study biofilm formation. S. cerevisiae strain belonging to genetic background Σ [sigma] 1278b is capable of forming biofilms, on low density (0.3%) agar media. When grown at 25°[degree] C for 5 days, it develops ...

Small Interfering Rna-Mediated Translation Repression Alters Ribosome Sensitivity To Inhibition By Cycloheximide In Chlamydomonas Reinhardtii, Xinrong Ma

Dissertations and Theses in Biological Sciences

RNA interference (RNAi) is an evolutionarily conserved gene silencing mechanism in eukaryotes, with regulatory roles in a variety of biological processes, including cell cycle, cell differentiation, physiological and metabolic pathways, and stress responses. RNAi can function by transcriptional silencing, mRNA target cleavage, translation repression and/or DNA elimination. In this study, we used the unicellular green alga Chlamydomonas reinhardtii as a model system to study RNAi-mediated translation repression. We demonstrated that small RNAs (sRNAs) generated from exogenously introduced inverted repeat transgenes, with perfect complementarity to the 3’UTR of a target transcript, can inhibit protein synthesis, without or with only ...

Functional Analysis Of A Putative Membrane-Bound Endo-Β-1,4-Glucanase From Panicum Virgatum, Joshua N Grant, Jonathan D. Willis, Neal Stewart

EURēCA: Exhibition of Undergraduate Research and Creative Achievement

Cellulose is the most abundant carbohydrate in the world and is degraded by the synergistic action of multiple enzymes. One large family of enzymes capable of hydrolyzing cellulose is glycoside hydrolase family 9 (GH9), which includes several endoglucanases. Recent research into the molecular biology of plants has revealed certain genes coding for endo-β-1,4-glucanases (EGases). The EGases in plants are primarily functional during cell elongation through wall stress relaxation. GH9 enzymes have been found in insects, bacteria, oomycetes, and fungi. In insects, EGases enable the organism to digest cellulose; in fungi, EGases are suspected to play an important role in ...

Apoptosis Is Signalled Early By Low Doses Of Ionizing Radiation In A Radiation-Induced Bystander Effect, Hayley Furlong, Carmel Mothersill, Fiona Lyng, Orla Howe

Articles

It is known that ionising radiation (IR) induces a complex signalling apoptotic cascade post-exposure to low doses ultimately to remove damaged cells from a population, specifically via the intrinsic pathway. Therefore, it was hypothesised that bystander reporter cells may initiate a similar apoptotic response if exposed to low doses of IR (0.05 Gy and 0.5 Gy) and compared to directly irradiated cells. Key apoptotic genes were selected according to their role in the apoptotic cascade; tumour suppressor gene TP53, pro-apoptotic Bax and anti-apoptotic Bcl2, pro-apoptotic JNK and anti-apoptotic ERK, initiator caspase 2 and 9 and effector caspase 3 ...

Characterization Of Hlh-29’S Reproductive Functions In Caenorhabditis Elegans, Thai Q. Tran Tt

Georgia State Undergraduate Research Conference

No abstract provided.

Construction Of A Tetracycline-Inducible System For Controlled Gene Expression In Crithidia Fasciculata, Fatima I. Hussain, Sanela Andelija

Georgia State Undergraduate Research Conference

No abstract provided.

Investigating The Functional Significance Of Evolutionarily Conserved Protein Motifs Of The Drosophila Melanogaster Hox Protein, Sex Combs Reduced, Lovesha Sivanantharajah

University of Western Ontario - Electronic Thesis and Dissertation Repository

Bilaterans share a common anterior-posterior (A-P) axis that is patterned by the Homeotic selector (Hox) genes. In Drosophila melanogaster, Hox gene expression in spatially restricted domains along the A-P axis of the embryo determines segmental identity. Identifying the genetic mechanisms of HOX control of development is essential for understanding body patterning in animals. I identified and characterized the role of evolutionarily conserved protein domains of the HOX protein, Sex combs reduced (SCR), in protein function. SCR is required for establishing the identity of both the labial and prothoracic segments. To identify regions of functional importance, 15 Scr point mutant alleles ...

Malnutrition In Sickle Cell Anemia: Implications For Infection, Growth And Maturation, Hyacinth I. Hyacinth, Oluwatoyosi A. Adekeye, Christopher S. Yilgwan

Journal of Social, Behavioral, and Health Sciences

Sickle cell anemia (SCA) is a genetic disease that affects mostly individuals of African and/or Hispanic descent, with the majority of cases in sub-Saharan Africa. Individuals with this disease show slowed growth, delayed sexual maturity, and poor immunologic function. These complications could partly be explained by the state of undernutrition associated with the disease. Proposed mechanism of undernutrition include protein hypermetabolism, decreased dietary intake possibly from interleukin-6-related appetite suppression, increased cardiac energy demand/expenditure, and increased red cell turnover. All the above mechanisms manifest as increased resting energy expenditure. Nutritional intervention utilizing single or multiple nutrient supplementation has led ...

Characterization And Distribution Of Novel Non-Ltr Retroelements Driving High Telomere Rflp Diversity In Clonal Lines Of Magnaporthe Oryzae, John H. Starnes

Theses and Dissertations--Plant Pathology

The filamentous ascomycete fungus Magnaporthe oryzae is a pathogen of over 50 genera of grasses. Two important diseases it can cause are gray leaf spot in Lolium perenne (perennial ryegrass) and blast in Oryza sativa (rice). The telomeres of M. oryzae isolates causing gray leaf spot are highly variable, and can spontaneously change during fungal culture. In this dissertation, it is shown that a rice-infecting isolate is much more stable at the telomeres than an isolate from gray leaf spot. To determine the molecular basis of telomere instability several gray leaf spot isolates telomeres were cloned, which revealed two non-LTR ...

A Synthetic Interaction Screen Identifies Factors Selectively Required For Proliferation And Tert Transcription In P53-Deficient Human Cancer Cells, Li Xie, Claude Gazin, Sung Mi Park, Lihua Julie Zhu, Marie-Anne Debily, Ellen L. W. Kittler, Maria L. Zapp, David S. Lapointe, Stephane Gobeil, Ching-Man A. Virbasius, Michael R. Green

Open Access Articles

Numerous genetic and epigenetic alterations render cancer cells selectively dependent on specific genes and regulatory pathways, and represent potential vulnerabilities that can be therapeutically exploited. Here we describe an RNA interference (RNAi)-based synthetic interaction screen to identify genes preferentially required for proliferation of p53-deficient (p53-) human cancer cells. We find that compared to p53-competent (p53+) human cancer cell lines, diverse p53- human cancer cell lines are preferentially sensitive to loss of the transcription factor ETV1 and the DNA damage kinase ATR. In p53- cells, RNAi-mediated knockdown of ETV1 or ATR results in decreased expression of the telomerase catalytic subunit ...

Ssrb-Dependent Regulation During Salmonella Pathogenesis, Ana M. Tomljenovic-Berube

Open Access Dissertations and Theses

Bacteria demonstrate an extraordinary capacity to survive and adapt to changing environments. In part, this ability to adapt can be attributed to horizontal gene transfer, a phenomenon which introduces novel genetic information that can be appropriated for use in particular niches. Nowhere is this more relevant than in pathogenic bacteria, whose acquisition of virulence genes have provided an arsenal that permits them to thrive within their selected host. Regulatory evolution is necessary for timely regulation of these acquired virulence genes in the host environment. Salmonella enterica serovar Typhimurium is an intracellular pathogen which possesses numerous horizontally-acquired genomic islands encoding pathogenic ...

Genetic Interactions Of Factors That Regulate Alternative Rna Splicing In The Male Germ Line Of Drosophila, Shanzhi Wang

UT GSBS Dissertations and Theses (Open Access)

Alternative RNA splicing is a critical process that contributes variety to protein functions, and further controls cell differentiation and normal development. Although it is known that most eukaryotic genes produce multiple transcripts in which splice site selection is regulated, how RNA binding proteins cooperate to activate and repress specific splice sites is still poorly understood. In addition how the regulation of alternative splicing affects germ cell development is also not well known. In this study, Drosophila Transformer 2 (Tra2) was used as a model to explore both the mechanism of its repressive function on its own pre-mRNA splicing, and the ...

A Genetic Survey Of English Sole Populations In The Salish Sea, Elizabeth S. Gutierrez, Gary A. Winans, Jon Baker, Amanda Cope

STEM Teacher and Researcher (STAR) Program Posters

This summer I interned at the Northwest Fisheries Science Center in Seattle, WA and participated in NOAA’s Salish Sea Project. The Salish Sea Project’s goal is to identify genetically distinctive groups of species in the Salish Sea that may have unique evolutionary and/or adaptive backgrounds. These findings will allow NOAA to promote and monitor the natural production of species in the Salish Sea, to select representative populations for experimental work regarding pollution, ocean acidification and climate change, to contribute to managing the ecosystem for intra- and inter-species diversity, and to help make informed decisions about adaptive management ...

Heterologous Complementation In Yeast Reveals The Solute Specificity Of A Nucleobase Cation Symporter 1 (Ncs1) From Nicotiana Tabacum, Jaclyn N. Nguyen

Master's Theses

The use and importance of nucleobases and nucleosides can never be understated due to their plethora of contribution to the vitality of all organisms. Their de novo synthesis and salvage is compartmentalized within cells, and their transport intercellular transport serves the biochemical needs of distant cells. This intra- and inter-cellular type of communication is mediated by nucleobase/nucleoside transporters, which are ubiquitous in life. The necessity of transporters is reflected in all genomes, which can code up to 10% of proteins involved with transport. In Arabidiopsis thaliana alone, there are six families have been shown to code for transporters of ...

Strategies To Investigate The Role Of Epcam In Cancer Stem Cells Of Breast Cancer Cell Lines, Ali Lessan

Open Access Dissertations and Theses

Based on the cancer stem cell (CSC) model, tumors develop as a hierarchy, much like normal tissue. At the apex, CSCs are capable of self-renewal and differentiating into non-tumorigenic cells that form the bulk of the tumor. CSCs have been isolated for many types of cancer based on cell surface marker expression. For instance in human breast carcinoma, the CD44+ CD24-/low EpCAM+ population are enriched in CSCs. These cells are more resistant to traditional chemo and radiation therapy relative to the bulk of the tumor. As such, many believe CSCs to be responsible for relapse and metastasis events. Hence ...