Molecular Genetics Commons^™

High Diversity Of Trypanosoma Cruzi Discrete Typing Units Circulating In Triatoma In Western Mexico, Uyen T. Nguyen

All Master's Theses

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi, which is transmitted to domestic and sylvatic mammals via the feces of hematophagous hemiptera of the subfamily Triatominae (Reduviidae). Trypanosoma cruzi is found only in the Americas and displays remarkable genetic diversity. Seven discrete typing units (DTUs) are currently recognized (TcI–TcVI and TcBat). In Jalisco, Mexico, where Chagas disease has a high prevalence rate, TcI has historically been the only DTU reported. This study focused on the molecular identification of T. cruzi DTUs circulating in Triatoma near the Estación de Biología Chamela, on the southwest coast of Jalisco, Mexico. …

Impact Of Transcription Factors On Fibroblast Specific Gene Silencing In Somatic Cell Hybrids, Tania Ray

Masters Theses

As totipotent cells differentiate to specific cell types in multicellular organisms, certain sets of genes are turned off (gene silencing/gene extinction) while others are turned on (gene activation). Cell type specific gene silencing and gene activation is the basis of cell differentiation. Somatic cell hybrids which are produced by fusing different types of somatic cells from two different tissues have been used as a valuable resource to discern the phenomenon of lineage- specific gene extinction. Identification of regulatory factors that mediate gene extinction in hybrids are key to understanding regulatory mechanisms that govern cell differentiation in a multicellular organism. Transcription …

Molecular Mechanism Of The Priming By Jasmonic Acid Of Specific Dehydration Stress Response Genes In Arabidopsis, Ning Liu, Zoya Avramova

School of Biological Sciences: Faculty Publications

Background: Plant genes that provide a different response to a similar dehydration stress illustrate the concept of transcriptional ‘dehydration stress memory’. Pre-exposing a plant to a biotic stress or a stress-signaling hormone may increase transcription from response genes in a future stress, a phenomenon known as ‘gene priming’. Although known that primed transcription is preceded by accumulation of H3K4me3 marks at primed genes, what mechanism provides for their appearance before the transcription was unclear. How augmented transcription is achieved, whether/how the two memory phenomena are connected at the transcriptional level, and whether similar molecular and/or epigenetic mechanisms regulate them are …

Transcriptional Regulation Of Dual-Specificity Phosphatase 4 (Dusp4) By Muscle Ring Finger 1 (Murf1) And Myogenic Regulatory Factors, Ashley Noel Haddock

UNF Graduate Theses and Dissertations

Skeletal muscle atrophy can occur at any age and as a result of numerous physiological conditions and thus, it was necessary to better identify the molecular underpinnings of the atrophy cascade so that new therapeutic targets to treat muscle wasting might be identified. MuRF1 was first identified as a marker of skeletal muscle atrophy over a decade ago; however, recent work suggests that this E3 ubiquitin ligase may participate in muscle wasting by regulating the transcriptional activity of genes differentially expressed in response to muscle atrophy. Dusp4, a dual-specificity phosphatase and member of the MAPK cascade, is induced in response …

Rna Sequencing Analysis Of The Msl2msl3, Crl, And Ggps1 Mutants Indicates That Diverse Sources Of Plastid Dysfunction Do Not Alter Leaf Morphology Through A Common Signaling Pathway, Darron R. Luesse, Margaret E. Wilson, Elizabeth S. Haswell

Biology Faculty Research

Determining whether individual genes function in the same or in different pathways is an important aspect of genetic analysis. As an alternative to the construction of higher-order mutants, we used contemporary expression profiling methods to perform pathway analysis on several Arabidopsis thaliana mutants, including the mscS-like (msl)2msl3 double mutant. MSL2 and MSL3 are implicated in plastid ion homeostasis, and msl2msl3 double mutants exhibit leaves with a lobed periphery, a rumpled surface, and disturbed mesophyll cell organization. Similar developmental phenotypes are also observed in other mutants with defects in a range of other chloroplast or mitochondrial functions, including …

Epacs: Epigenetic Regulators That Affect Cell Survival In Cancer., Catherine Murari

Theses & Dissertations

Cyclic adenosine monophosphate (cAMP) is a second messenger responsive to many external stimuli, playing an important role in cellular gene expression, metabolism, migration, differentiation, hypertrophy, apoptosis and secretion. All of these cellular functions are important in many diseases including cancer. Most of its effects were initially attributed to the classical protein kinase A (PKA) protein, but cellular functions such as proliferation and migration were found to be PKA independent and dependent on the newly discovered exchange proteins directly activated by cAMP (EPACs). EPACs are single polypeptides that primarily function as guanine exchange factors (GEFs) for Rap proteins that allow the …

The Development Of A Platform For Expression And Purification Of The Mammalian Transmembrane Transporter Abca4, Amaryllis Ortiz

Graduate School of Biomedical Sciences Theses and Dissertations

Purpose- ABCA4 is an ATP Binding Cassette (ABC) protein localized at cone and rod photoreceptor outer segments of the retina. Though mutations in ABCA4 have been found to cause a broad spectrum of disorders, ABCA4's high molecular weight (~210 kDa) and biochemical transmembrane properties have made ABCA4 functional studies unsuccessful. Identifying how ABCA4 functions might have significant clinical impact and open unanticipated avenues for therapeutic interventions. Thus, the objective of this study was to develop a new expression system able to produce the full-length, correctly folded and fully functional ABCA4 protein.

Methods- the ABCA4 gene was amplified from the PCMV6-ABCA4 …

Role Of B Cell Receptor Signaling In Il-10 Production By Normal And Malignant B-1 Cells., Sara S Alhakeem, Vishal J Sindhava, Mary K Mckenna, Beth W Gachuki, John C Byrd, Natarajan Muthusamy, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

B-1 cells are considered innate immune cells, which produce the majority of natural antibodies. B-1 cell responses to B cell receptor (BCR) and Toll-like receptor ligation are tightly regulated owing to the cross-reactivity to self-antigens. CD5 has been shown to play a major role in downregulation of BCR responses in B-1 cells. Here, we provide evidence for another mechanism by which BCR response is regulated in B-1 cells. B-1 cells, as well as their malignant counterpart, B cell chronic lymphocytic leukemia (B-CLL) cells, produce interleukin-10 (IL-10) constitutively. IL-10 secretion by normal B-1 cells downregulates their proliferation responses to BCR ligation. …

Post Operative Fungal Endopthalmitis Due To Geotrichum Candidum, Thein Myint, Matthew J. Dykhuizen, Carolyn H. Mcdonald, Julie A. Ribes

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Geotrichum species have been rarely reported as the cause of sepsis, disseminated infection in immunosuppressed patients. The patient we describe developed indolent endophthalmitis four months after her routine right eye cataract surgery. The intraoperative sample from right vitreous fluid grew Geotrichum candidum. The patient underwent vitrectomy, artificial lens explantation and intravitreal injection of amphotericin B followed by oral voriconazole. Despite these interventions, she underwent enucleation. This is the first published case of Geotrichum candidum endophthalmitis.

Efficacy Of Galactooliosaccharide (Gos) And/Or Rhamnose-Based Synbiotics In Enhancing Ecological Performance Of Lactobacillus Reuteri In The Human Gut And Characterization Of Its Gos Metabolic System, Monchaya Rattanaprasert

Department of Food Science and Technology: Dissertations, Theses, and Student Research

Probiotic L. reuteri has potential to produce antimicrobial compounds and secrete immunosuppressive factors. These metabolic attributes could benefit the human host by providing colonization resistance (competitive and metabolic exclusion) against enteropathogens and mitigating inflammation. As metabolically active cells are fundamental to such probiotic properties, synbiotic approaches that supply L. reuteri with a source(s) of carbon, energy, and/or external electron acceptor for cell growth in the gut environment could therefore prompt the probiotic to engage in beneficial activities. In this study, the efficacy of GOS and/or rhamnose-based synbiotic approaches in promoting colonization persistence and metabolic activity of L. reuteri was evaluated. …

Preventing Thymus Involution In K5.Cyclin D1 Transgenic Mice Sustains The Naïve T Cell Compartment With Age, Michelle L. Bolner

Dissertations and Theses (Open Access)

The thymus maintains T cell receptor (TCR) repertoire diversity through perpetual release of self-MHC restricted naive T cells. However, thymus involution during the aging process reduces naïve T cell output, leading to defective immune responsiveness to newly encountered antigens. We have found that early thymus involution precipitates the age-associated shift favoring memory T cell dominancy in young control mice. Furthermore, we have shown that age-related thymus involution is prevented in mice expressing a keratin 5 promoter-driven Cyclin D1 (K5.D1) transgene in thymic epithelial cells (TECs). Thymopoiesis occurs normally in K5.D1 transgenic thymi and sustains T cell output to prevent the …

In Vivo Functional Significance Of Ccat2 Long Non-Coding Rna In Myelodysplastic Syndrome, Maitri Y. Shah

Dissertations and Theses (Open Access)

Long non-coding RNAs form the largest part of the mammalian non-coding transcriptome and control gene expression at various levels including chromatin modification, transcriptional and post-transcriptional processing. Although the underlying molecular mechanisms are not yet entirely understood, lncRNAs are implicated in initiation and progression of several cancers. CCAT2 is a lncRNA that spans the highly conserved 8q24 region associated with increased risk for various cancers. CCAT2 has been shown to play an important role in inducing chromosomal instability and supporting cell proliferation and cell cycle arrest. However, a causal role of CCAT2 in initiation of tumorigenesis and the importance of G/T …

Genetic Analyses Determine Connectivity Among Cave And Surface Populations Of The Jamaican Endemic Freshwater Crab Sesarma Fossarum In The Cockpit Country, Manuel Stemmer, Christoph D. Schubart

International Journal of Speleology

The Jamaican freshwater crab Sesarma fossarum (Decapoda: Brachyura: Sesarmidae) is endemic to western central Jamaica where it occurs in cave and surface streams of karst regions. In the present study, we examine the population genetic structure of the species, providing evidence for intraspecific differentiation and genetic substructure among twelve sampled populations. Interestingly, crabs from caves appear genetically undistinguishable from representatives of nearby surface waters, despite previously observed and described morphometric differentiation. In contrast, genetic isolation takes place among populations from rivers and caves belonging to different watersheds. In one case, even populations from different tributaries of the same river were …

Tuberculosis And Cardiovascular Disease: Linking The Epidemics, Moises A. Huaman, David Henson, Eduardo Ticona, Timothy R. Sterling, Beth A. Garvy

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The burden of tuberculosis and cardiovascular disease (CVD) is enormous worldwide. CVD rates are rapidly increasing in low- and middle-income countries. Public health programs have been challenged with the overlapping tuberculosis and CVD epidemics. Monocyte/macrophages, lymphocytes and cytokines involved in cellular mediated immune responses against Mycobacterium tuberculosis are also main drivers of atherogenesis, suggesting a potential pathogenic role of tuberculosis in CVD via mechanisms that have been described for other pathogens that establish chronic infection and latency. Studies have shown a pro-atherogenic effect of antibody-mediated responses against mycobacterial heat shock protein-65 through cross reaction with self-antigens in human vessels. Furthermore, …

Reactive Oxygen Species-Mediated Neurodegeneration Is Independent Of The Ryanodine Receptor In Caenorhabditis Elegans, Lyndsay E.A. Young, Daniel C. Williams

Journal of the South Carolina Academy of Science

Despite the significant impacts on human health caused by neurodegeneration, our understanding of the degeneration process is incomplete. The nematode Caenorhabditis elegans is emerging as a genetic model organism well suited for identification of conserved cellular mechanisms and molecular pathways of neurodegeneration. Studies in the worm have identified factors that contribute to neurodegeneration, including excitotoxicity and stress due to reactive oxygen species (ROS). Disruption of the gene unc-68, which encodes the ryanodine receptor, abolishes excitotoxic cell death, indicating a role for calcium (Ca²⁺) signaling in neurodegeneration. We tested the requirement for unc-68 in ROS-mediated neurodegeneration using the …

Mutations Of Adjacent Amino Acid Pairs Are Not Always Independent, Jyotsna Ramanan, Peter Revesz

School of Computing: Conference and Workshop Papers

Evolutionary studies usually assume that the genetic mutations are independent of each other. This paper tests the independence hypothesis for genetic mutations with regard to protein coding regions. According to the new experimental results the independence assumption generally holds, but there are certain exceptions. In particular, the coding regions that represent two adjacent amino acids seem to change in ways that sometimes deviate significantly from the expected theoretical probability under the independence assumption.

Flavodoxin-Like Proteins Protect Candida Albicans From Oxidative Stress And Promote Virulence, Lifang Li, Shamoon Naseem, Sahil Sharma, James B. Konopka

Department of Molecular Genetics and Microbiology Faculty Publications

The fungal pathogen Candida albicans causes lethal systemic infections in humans. To better define how pathogens resist oxidative attack by the immune system, we examined a family of four Flavodoxin-Like Proteins (FLPs) in C. albicans. In agreement with previous studies showing that FLPs in bacteria and plants act as NAD(P)H quinone oxidoreductases, a C.albicans quadruple mutant lacking all four FLPs (pst1Δ, pst2Δ, pst3Δ, ycp4Δ) was more sensitive to benzoquinone. Interestingly, the quadruple mutant was also more sensitive to a variety of oxidants. Quinone reductase activity confers important antioxidant effects because resistance …

Borrelia Burgdorferi Reva Significantly Affects Pathogenicity And Host Response In The Mouse Model Of Lyme Disease, Rebecca Byram, Robert A. Gaultney, Angela M. Floden, Christopher Hellekson, Brandee L. Stone, Amy Bowman, Brian Stevenson, Barbara J. B. Johnson, Catherine A. Brissette

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The Lyme disease spirochete, Borrelia burgdorferi, expresses RevA and numerous outer surface lipoproteins during mammalian infection. As an adhesin that promotes bacterial interaction with fibronectin, RevA is poised to interact with the extracellular matrix of the host. To further define the role(s) of RevA during mammalian infection, we created a mutant that is unable to produce RevA. The mutant was still infectious to mice, although it was significantly less well able to infect cardiac tissues. Complementation of the mutant with a wild-type revA gene restored heart infectivity to wild-type levels. Additionally, revA mutants led to increased evidence of arthritis, …

Muscle Weakness During Aging: A Deficiency State Involving Declining Angiogenesis, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

This essay begins by proposing that muscle weakness of old age from sarcopenia is due in large part to reduced capillary density in the muscles, as documented in 9 reports of aged persons and animals. Capillary density (CD) is determined by local levels of various angiogenic factors, which also decline in muscles with aging, as reported in 7 studies of old persons and animals. There are also numerous reports of reduced CD in the aged brain and other studies showing reduced CD in the kidney and heart of aged animals. Thus a waning angiogenesis throughout the body may be …

Drosophila Eye Model To Study Neuroprotective Role Of Creb Binding Protein (Cbp) In Alzheimer’S Disease, Timothy Cutler, Ankita Sarkar, Michael Moran, Andrew Steffensmeier, Oorvashi Roy Puli, Greg Mancini, Meghana Tare

Biology Faculty Publications

Background: The progressive neurodegenerative disorder Alzheimer’s disease (AD) manifests as loss of cognitive functions, and finally leads to death of the affected individual. AD may result from accumulation of amyloid plaques. These amyloid plaques comprising of amyloid-beta 42 (Aβ42) polypeptides results from the improper cleavage of amyloid precursor protein (APP) in the brain. The Aβ42 plaques have been shown to disrupt the normal cellular processes and thereby trigger abnormal signaling which results in the death of neurons. However, the molecular-genetic mechanism(s) responsible for Aβ42 mediated neurodegeneration is yet to be fully understood.

Methodology/Principal Findings: We have utilized Gal4/UAS system to …