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Immunology and Infectious Disease

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Full-Text Articles in Molecular Biology

Nascent Dna Proteomics Analysis Uncovers Dna Replication Dynamics In The Human Pathogen Trypanosoma Brucei, Maria Rocha Granados Jan 2019

Nascent Dna Proteomics Analysis Uncovers Dna Replication Dynamics In The Human Pathogen Trypanosoma Brucei, Maria Rocha Granados

Doctoral Dissertations

DNA is the substrate of many cellular processes including DNA replication, transcription and chromatin remodeling. These processes are coordinated to maintain genome integrity and ensure accurate duplication of genetic and epigenetic information. Genome-wide studies have provided evidence of the relationship between transcription and DNA replication timing. A global analysis of DNA replication initiation in T. brucei showed that TbORC1 (subunit of the origin recognition complex, ORC) binding sites are located at the boundaries of transcription units. Although recent studies in T. brucei indicate functional links among DNA replication and transcription, the underlying mechanisms remain unknown. In this study, we adapted ...


Characterization Of Interleukin (Il)-1Β Regulatory Elements And Chromatin Conformation In Macrophage Activation, Woohyun Cho Aug 2018

Characterization Of Interleukin (Il)-1Β Regulatory Elements And Chromatin Conformation In Macrophage Activation, Woohyun Cho

Electronic Thesis and Dissertation Repository

IL-1β is a potent inflammatory cytokine promptly expressed in activated myeloid cells. PU.1 is a lineage-determining transcription factor that regulates myeloid-specific genes by activating distal enhancers. This study addresses the functional importance of a potential enhancer of IL-1β, and how PU.1 regulates its activity state. A putative enhancer RNA (eRNA) was transcribed from the enhancer, and eRNA knock-down with antisense oligonucleotides inhibited IL-1β production. Furthermore, enhancer-promoter interactions in stimulated macrophages were detected via chromatin conformation capture (3C) analysis. The role of PU.1 was examined in PU.1-overexpressed B16-BL6 cells, which responded to LPS and expressed IL-1β mRNA ...


Production Of A Candidate Recombinant Protein Vaccine For Mannheimia Haemolytica In Lettuce And Tobacco Chloroplasts, Coby K. Martin Jul 2018

Production Of A Candidate Recombinant Protein Vaccine For Mannheimia Haemolytica In Lettuce And Tobacco Chloroplasts, Coby K. Martin

Electronic Thesis and Dissertation Repository

The cattle industry worldwide is ravaged by bovine respiratory disease (BRD), a bacterial disease caused by Mannheimia haemolytica. Recent efforts to design vaccines against M. haemolytica focus on a virulence factor, leukotoxin, in addition to surface lipoproteins. Plant-based protein production is a safe and inexpensive alternative to traditional methods. Edible vaccines deliver antigens to pharyngeal tissues, which can provide local immunization against M. haemolytica prior to its progression into the lungs. In this project, a chimeric protein containing M. haemolytica antigens was produced in tobacco chloroplasts as a candidate edible vaccine for BRD. Attempts were made to transform lettuce chloroplasts ...


Investigation Of Bradyzoite Differentiation Initiation In Toxoplasma Gondii, Harim I. Won, Paul H. Davis Ph.D. May 2018

Investigation Of Bradyzoite Differentiation Initiation In Toxoplasma Gondii, Harim I. Won, Paul H. Davis Ph.D.

Theses/Capstones/Creative Projects

Like other eukaryotic organisms, Toxoplasma gondii promoters feature both constitutive and life-stage regulated cis-elements. Using a transcriptomic microarray approach, a cluster of transcripts upregulated early during bradyzoite differentiation was identified. Computational analysis of the promoter regions of these “up-early” transcripts identified a shared upstream consensus motif, a putative transcription factor binding site. Using a dual luciferase assay adapted for recombinational cloning and reporter gene quantification by qPCR, we demonstrate developmental stage-specific expression of the luciferase reporter gene inserted downstream of the transcription factor binding site. The shared consensus motif was found to be an autonomous cis-element by conversion ...


Investigating The Role Of Rna-Binding Protein 5 In The Life Cycle Differentiation Of Trypanosoma Brucei, David Anaguano Pillajo Jan 2018

Investigating The Role Of Rna-Binding Protein 5 In The Life Cycle Differentiation Of Trypanosoma Brucei, David Anaguano Pillajo

Masters Theses

Trypanosomatid parasites such as Trypanosoma brucei have unusual mechanisms of gene expression including polycistronic transcription, mitochondrial RNA editing and trans-splicing. Additionally, these protists rely mainly on post-transcriptional regulation where RNA-binding proteins (RBP) have shown to play a major role. RBP6 and RBP10 are two examples of RBPs that play crucial roles in procyclic and bloodstream form parasites differentiation respectively, by post-transcriptional regulation. Over-expression of RBP6 is enough to promote differentiation into metacyclic trypomastigotes that are infective to mice. However, continuous expression is required, and this pattern does not reflect the natural expression in the tsetse fly or the influence of ...


Relationships Between Factors Influencing Biofilm Formation And Pathogen Retention In Complex Rhizosphere Microbial Communities, Aaron Coristine Jan 2018

Relationships Between Factors Influencing Biofilm Formation And Pathogen Retention In Complex Rhizosphere Microbial Communities, Aaron Coristine

Theses and Dissertations (Comprehensive)

Riparian wetlands are unique habitats facilitating all forms of life. The riverbanks of these environments provide ideal conditions for bacteria, plants, and higher organisms. Of particular interest to this research was the variation in microbial community structure at high, intermediate and poor water quality impacted areas. Assessing the capabilities of plants to retain microbial pathogens was identified. Root systems and corresponding soil are ideal locations for bacterial deposition, resulting in attachment at these areas. Biofilm production in these regions is important for long-term establishment, leading to persistence and potential naturalization. Opportunistic pathogens originating from mammalian fecal matter are introduced into ...


Gene Therapy Approaches To Immune Tolerance Induction In Canine Hemophilia, Robert French Jan 2018

Gene Therapy Approaches To Immune Tolerance Induction In Canine Hemophilia, Robert French

Publicly Accessible Penn Dissertations

A key issue in gene therapy is the immune response to the therapeutic transgene. This is especially important in applications where current treatments often elicit an antibody response, like hemophilia, where protein replacement therapy results in neutralizing

antibodies (“inhibitors”) in ~25% of severe hemophilia A and 1-3% of severe hemophilia B patients. To test the ability of skeletal muscle-directed gene therapy to prevent an immune response, we used an inhibitor-prone dog model of severe hemophilia B to express a hyperactive factor IX (FIX) variant from skeletal muscle via adeno-associated viral (AAV) vector and observed curative levels of expression that lasted ...


Impact Of Acute Heat Treatment On Autophagy And Insulin Signaling In C2c12 Myotubes, Corey Michael Summers Jan 2018

Impact Of Acute Heat Treatment On Autophagy And Insulin Signaling In C2c12 Myotubes, Corey Michael Summers

Graduate Theses and Dissertations

A major risk factor for the development of type 2 diabetes is reduced skeletal muscle insulin sensitivity. It is known that exercise and caloric restriction can improve skeletal muscle insulin resistance, but the mechanism by which this occurs is not completely elucidated. The AMP-activated protein kinase (AMPK), is thought to be a major contributor to the metabolic benefits observed after exercise training and caloric restriction. Activation of AMPK in skeletal muscle can have a wide range of effects, one of which is the initiation of macroautophagy (herein referred to as autophagy). Autophagy is the bulk degradation system of the cell ...


Type Ix Secretion System : Characterization Of An Effector Protein And An Insight Into The Role Of C-Terminal Domain Dimeration In Outer Membrane Translocation., Lahari Koneru Dec 2017

Type Ix Secretion System : Characterization Of An Effector Protein And An Insight Into The Role Of C-Terminal Domain Dimeration In Outer Membrane Translocation., Lahari Koneru

Electronic Theses and Dissertations

Porphyromonas gingivalis and Tannerella forsythia are two of the primary pathogens that are associated in the etiology and progression of chronic periodontitis. In T. forsythia, KLIKK proteases are the recently identified group of proteolytic enzymes that are secreted through Type IX secretion system (T9SS). Among, these KLIKK proteases a synergistic relationship was observed between karilysin and mirolysin in invading the host complement system for the survival of the bacteria. Since, karilysin has been already characterized, in this study we propose to study about mirolysin through structural, biochemical and biological characterization. The obtained results from the experiments has shown the propensity ...


Effects Of Carboxylated Nanodiamonds On Macrophages During And After Differentiation, Maisoun E. Bani Hani Oct 2017

Effects Of Carboxylated Nanodiamonds On Macrophages During And After Differentiation, Maisoun E. Bani Hani

Biological Sciences Theses & Dissertations

Nanodiamonds (ND) are a carbon-based nanomaterial that are increasingly being proposed for developing novel imaging techniques, as carriers of biomolecules and therapeutic drugs, as coatings for implants, and for other biomedical applications. The exceptional chemical, mechanical, and optical properties of ND make this material suitable in a wide range of fields. The application of ND in the biomedical field is attractive but requires more in-depth investigation into the safety of ND and its interactions with different cells and systems. The effects of ND on the immune system are not fully understood or investigated and there are several controverting reports regarding ...


Rational Drug Design Directed At Blocking The Initial Signaling Events In Lipopolysaccharide-Induced Sepsis., Christopher A. Tipton Jul 2017

Rational Drug Design Directed At Blocking The Initial Signaling Events In Lipopolysaccharide-Induced Sepsis., Christopher A. Tipton

Theses

Systemic Inflammatory Response Syndrome (SIRS) is classified as an immune system response to an infectious state. If left untreated, SIRS leads to sepsis, septic shock, end-organ dysfunction, and death. As a patient progresses through these stages, associations of acute respiratory distress, disseminated intravascular coagulation, and acute renal failure persist, resulting in millions of deaths annually. Lipopolysaccharide (LPS), a bacterial endotoxin, is released into the blood stream, triggering SIRS. LPS is found in the outer cell-wall of Gram-negative bacteria and is responsible for initiation of a devastating cytokine storm. One of the regions of LPS, lipid A, is a polyacylated glucosamine ...


Evolutionary Genetic Aspects Of Host Association In Generalist Ectoparasites, Benoit Talbot May 2017

Evolutionary Genetic Aspects Of Host Association In Generalist Ectoparasites, Benoit Talbot

Electronic Thesis and Dissertation Repository

Despite the use of the host for dispersal by most parasite species, the extremely loose relationship typical between highly mobile hosts and generalist ectoparasites may lead to very different gene flow patterns between the two, leading in turn to different spatial genetic structure, and potentially different demographic history. I examined how similar gene flow patterns are between Cimex adjunctus, a generalist ectoparasite of bats present throughout North America, and two of its key bat hosts. I first analyzed the continent-scale genetic structure and demographic history of C. adjunctus and compared it to that of two of its hosts, the little ...


B7h6: A Cancer Biomarker For The Development Of Novel Immunotherapy Approaches, Mariana Phillips May 2017

B7h6: A Cancer Biomarker For The Development Of Novel Immunotherapy Approaches, Mariana Phillips

Seton Hall University Dissertations and Theses (ETDs)

Cancer-based immunotherapy has led the evolution of biologics that can stimulate immune responses towards tumor eradication. The synthesis of small to intermediate size molecules with the targeting and effector functions of mAb may represent a novel class of immunotherapeutics that may overcome the limitations of their biological counterparts.Towards this objective, B7H6 has been identified as a protein ligand localized on the cell surface of transformed tumor cells. B7H6 binds specifically to the activating receptor NKp30, constitutively expressed on all resting and active NK cells. Upon ligand:receptor binding, B7H6 triggers NK cell activation and release of chemokines and pro-inflammatory ...


The Role Of Rna Interference In The Control Of Leishmania Rna Virus 1 Infection, Erin Acino Brettmann May 2017

The Role Of Rna Interference In The Control Of Leishmania Rna Virus 1 Infection, Erin Acino Brettmann

Arts & Sciences Electronic Theses and Dissertations

The presence of Leishmania RNA virus 1 (LRV1) in parasites of the Leishmania (Viannia) subgenus increases the virulence of the parasite in mouse models of leishmaniasis and is correlated with treatment failure, relapse, and the development of mucocutaneous disease in humans. LRV1 is not shed or infectious; rather, the infection is persistent, and as yet it is unknown how the parasite controls virus levels. Many eukaryotic organisms use RNA interference (RNAi) to limit virus replication, and Leishmania (Viannia) parasites have an active RNAi pathway. To determine whether Leishmania are capable of using RNAi to control LRV1, we sequenced sRNAs from ...


Validation Of The Pre-B Cell Receptor As A Therapeutic Target In B Cell Precursor Acute Lymphoblastic Leukemia, Michael F. Erasmus Apr 2017

Validation Of The Pre-B Cell Receptor As A Therapeutic Target In B Cell Precursor Acute Lymphoblastic Leukemia, Michael F. Erasmus

Biomedical Sciences ETDs

This dissertation is built upon the fundamental idea that the pre-B cell receptor (pre-BCR) is important to leukemia cell survival and a logical therapeutic target in B cell precursor acute lymphoblastic leukemia (BCP-ALL). The pre-BCR is expressed early at a specific stage during B cell development where it plays a central role in survival of healthy B lymphocytes. This receptor is composed of the membrane heavy chain (mIgμ) associated with surrogate light chain components, 5 and VpreB. Through the use of advanced imaging modalities, in particular two-color single particle tracking (SPT), we showed that pre-BCRs formed transient, homotypic interactions. These ...


Development Of Tools For Stable Transfection In The Human Filarial Parasite Brugia Malayi Via The Piggybac Transposon System, Johan Chabanon Mar 2017

Development Of Tools For Stable Transfection In The Human Filarial Parasite Brugia Malayi Via The Piggybac Transposon System, Johan Chabanon

Graduate Theses and Dissertations

Brugia malayi is one of three species of nematode known to cause lymphatic filariasis (LF) in humans. LF infects over 120 million people, causing debilitating disease. Various global programs have been launched in the past 20 years to eliminate LF. These programs have greatly scaled up the resources and efforts allocated to halting the transmission and reducing disease burden. Only a few drugs are used to treat LF, and resistance is thus a devastating possibility. Research aimed at identifying new drug targets could therefore prove essential in elimination of LF.

Genetic manipulation of B. malayi has been limited to transient ...


Impact Of Host Factors On The Adaptive Immune Response To Aav Gene Therapy, Scott N. Ashley Jan 2017

Impact Of Host Factors On The Adaptive Immune Response To Aav Gene Therapy, Scott N. Ashley

Publicly Accessible Penn Dissertations

Impact of host factor on the adaptive immune response to AAV gene therapy

Scott Ashley

James Wilson

Adaptive immune responses to the transgene product remain an active area of concern for the gene therapy field. How host factors can influence the activation of the immune system is an important consideration in the development of gene therapy for different genetic disorders. One factor considered by many to shape the adaptive immune response is an individual’s genotype. Nonsense mutations were thought to result in an absence of tolerance to a replacement protein provided by gene therapy, due to a lack of ...


Dna Double Strand Breaks Suppress Expression Of The Rag Recombinase: Mechanisms And Consequences, Megan Rose Fisher Jan 2017

Dna Double Strand Breaks Suppress Expression Of The Rag Recombinase: Mechanisms And Consequences, Megan Rose Fisher

Publicly Accessible Penn Dissertations

Developing B and T lymphocytes must rearrange the genomic sequence of antigen receptor genes by V(D)J recombination. The lymphocyte-specific endonuclease RAG, composed of Rag1 and Rag2, initiates this process by cleaving specific sites within antigen receptor loci. RAG expression must be carefully regulated to ensure that V(D)J recombination occurs only under appropriate circumstances. The Bassing laboratory has previously demonstrated that Igκ locus cleavage by RAG in pre-B cells initiates a feedback-inhibition signal suppressing RAG expression. Here, we show that DNA double strand breaks (DSBs) induced by a variety of genotoxic agents have a similar effect in ...


Inflammatory Gene Expression In Women Diagnosed With Polycystic Ovarian Syndrome, Myles K. Taylor Dec 2016

Inflammatory Gene Expression In Women Diagnosed With Polycystic Ovarian Syndrome, Myles K. Taylor

Electronic Thesis Collection

Polycystic ovarian syndrome (PCOS) is a common endocrine disorder in women of reproductive age. The pathophysiology of PCOS has conventionally thought to originate from androgen excess. However, recent evidence suggests that androgen excess is a downstream consequence to inflammatory dysregulation and subsequent metabolic abnormalities. Inflammatory mRNA gene expression of TNFa and IL-1ß in mononuclear cells isolated from women diagnosed with PCOS was explored using qPCR. Additionally, the correlations between body mass index (BMI) and fasting glucose on mRNA expression of TNFa and IL-1ß were explored. mRNA expression of both TNFa and IL-1ß were found to be significantly higher in PCOS ...


Molecular And Functional Analysis Of The Pixb Gene In Xenorhabdus Nematophila, John Lucas Dec 2016

Molecular And Functional Analysis Of The Pixb Gene In Xenorhabdus Nematophila, John Lucas

Theses and Dissertations

Xenorhabdus nematophila and the entomopathogenic nematode Steinernema carpocapsae form a mutualistic relationship facilitating the infection, death and consumption of an insect host. The infective juvenile (IJ) form of S. carpocapsae invades the insect host through natural openings and proceeds to the hemocoel where exposure to hemolymph stimulates the release of X. nematophila from the anterior vesicle. Excreted X. nematophila releases immunosuppressive compounds and insect toxins into the insect hemolymph that facilitates death of the host. As X. nematophila reaches high cell density it secretes exoenzymes that degrade insect tissues and produces antibiotics that reduce microbial competition. S. carpocapsae utilizes the ...


The Effects Of Phytohormones And Isoprenoids In Dihydroartemisinin-Induced Dormancy In The Erythrocytic Stages Of Plasmodium Falciparum, Marvin Duvalsaint Duvalsaint Nov 2016

The Effects Of Phytohormones And Isoprenoids In Dihydroartemisinin-Induced Dormancy In The Erythrocytic Stages Of Plasmodium Falciparum, Marvin Duvalsaint Duvalsaint

Graduate Theses and Dissertations

Our ability to control malaria has been challenged by increasing antimalarial resistance. Plasmodium falciparum undergoes dormancy in the blood stages which is hypothesized to be a means by which they are able to survive under drug pressure. This helps select for resistant parasites which grow following removal of drug. The mechanisms behind dormancy and the subsequent recrudescence are not fully understood but translating knowledge from related organisms which undergo a similar phenomenon might shed some light. Higher plants utilize dormancy during the early development stages to survive under unfavorable conditions, increasing fitness of the seedling and ensuring viability when this ...


Mitochondrial Heteroplasmy Contributes To The Dynamic Atovaquone Resistance Response In Plasmodium Falciparum, Sasha Victoria Siegel Nov 2016

Mitochondrial Heteroplasmy Contributes To The Dynamic Atovaquone Resistance Response In Plasmodium Falciparum, Sasha Victoria Siegel

Graduate Theses and Dissertations

Of the considerable challenges researchers face in the control and elimination of malaria, the development of antimalarial drug resistance in parasite populations remains a significant hurdle to progress worldwide. Atovaquone is used in combination with proguanil (Malarone) as an antimalarial treatment in uncomplicated malaria, but is rendered ineffective by the rapid development of atovaquone resistance during treatment. Previous studies have established that de novo mutant parasites confer resistance to atovaquone with a substitution in amino acid 268 in the cytochrome b gene encoded by the parasite mitochondrial genome, yet much is still unknown about how this resistance develops, and whether ...


The Rodent Parvovirus H-1 And Its Potential In Combination With Tien Hsien Liquid As A Treatment For Breast Cancer, Hayley I. Spires Nov 2016

The Rodent Parvovirus H-1 And Its Potential In Combination With Tien Hsien Liquid As A Treatment For Breast Cancer, Hayley I. Spires

Selected Honors Theses

Breast cancer is responsible for 12% of cancer diagnoses each year, and it is the leading cause of cancer-related mortality in women worldwide. Current treatments have provided some success in combatting the disease but are not considered a final solution. The framework for how researchers approach cancer has continued to change, and this includes the introduction of oncolytic viruses as novel therapeutics for cancer. The rodent parvovirus H-1 has shown strong potential in clinical and subclinical trials, but its S phase dependency limits its usefulness against cancer stem cell populations. Tien Hsien Liquid is commerically available, nontoxic, and has shown ...


Dynamic Host-Pathogen Interactions Result In Fungal Epitope Unmasking, Alex Hopke Aug 2016

Dynamic Host-Pathogen Interactions Result In Fungal Epitope Unmasking, Alex Hopke

Electronic Theses and Dissertations

Molecular camouflage is used by a diverse set of pathogens to disguise their identity and avoid recognition by protective host receptors. The opportunistic fungal pathogen Candida albicans is a good example, as it masks the inflammatory component β-glucan in its cell wall to evade detection by the immune receptor Dectin-1. Interestingly, it has been seen that β-glucan becomes unmasked during infection in vivo, though the underlying mechanisms remained unclear. Exposure levels of this epitope may be important, as Dectin-1 mediates protection from some strains of C. albicans and alterations in the organization and composition of the Candida cell wall can ...


Innate Immunity In Chickens: In Vivo Responses To Different Pathogen Associated Molecular Patterns, Kristen Alicia Byrne Aug 2016

Innate Immunity In Chickens: In Vivo Responses To Different Pathogen Associated Molecular Patterns, Kristen Alicia Byrne

Theses and Dissertations

Pattern recognition receptors (PRRs) on host cells recognize motifs known as pathogen associated molecular patterns (PAMPs) that are common to groups of microbes. Examples include LPS on Gram-negative bacteria, the structural motif PGN common to all bacteria, MDP the smallest immunostimulatory unit of PGN, and poly I:C the dsRNA analog. PAMP recognition by and stimulation of the innate immune system is crucial to an individual’s ability to quickly limit microbial growth and stimulate the adaptive immune system. Characterization of the in vivo immune responses initiated by PAMPs has not been directly addressed. Using growing feathers (GF) as a ...


Immune Modulating Functions By Soypeptide Lunasin In Cancer Immunotherapy, Chun-Yu Tung May 2016

Immune Modulating Functions By Soypeptide Lunasin In Cancer Immunotherapy, Chun-Yu Tung

Open Access Dissertations

Chemotherapy is currently the mainstay of treatment for most cancer patients. Despite its efficacy in eliminating cancer cells, a high percentage of chemotherapy patients eventually relapse or suffer progression of the disease. Immunosurveillance is capable of recognizing and eliminating continuously arising transformed mutant cells, and thus cancer immunotherapy is one of the emerging therapeutic strategies that harnesses the power of the immune system to eradicate chemotherapy-resistant cancerous cells. However, the adverse side effects of chemotherapy impede the therapeutic effects of immunotherapy. Our previous studies demonstrate that lymphoma patients are refractory to clinical immunotherapy because of chemotherapy-induced immune dysfunction. In addition ...


Preeclampsia: The Roles Of Acute Inflammation And Intrauterine Stress, Nicholas Parchim May 2016

Preeclampsia: The Roles Of Acute Inflammation And Intrauterine Stress, Nicholas Parchim

UT GSBS Dissertations and Theses (Open Access)

Preeclampsia (PE) is a severe, acute disease of pregnancy affecting approximately 8% of pregnant women after week 20 of gestation. PE is characterized by hypertension and renal damage reflected by proteinuria and has significant morbidity to both mother and fetus. Maternal symptoms range from headaches, nausea, edema, to visual changes, but once maternal symptoms present, damage to the fetus has begun. Mothers who progress untreated through the disease can also experience a condition called eclampsia characterized by seizure, coma, and, ultimately, death. PE-affected newborns experience features similar to prematurity—abnormal lung and renal development, intrauterine growth retardation (IUGR), and, possibly ...


Proteomic Characterization Of Eggshell Membranes And Their Effect On Poultry Physiology And Immunity, Sarbjeet Kaur Makkar May 2016

Proteomic Characterization Of Eggshell Membranes And Their Effect On Poultry Physiology And Immunity, Sarbjeet Kaur Makkar

Theses and Dissertations

The use of antibiotics in poultry growth and disease control has led to antibiotics resistant problem in human beings, which is a big concern among consumers. With the necessity for judicious use of antibiotics in poultry production, alternative strategies to improve disease resistance in poultry production are necessary. The research is more inclined towards using the natural products available to grow healthier and antibiotic free meat animals. In the context of exploring natural and sustainable resource of alternative to antibiotics, the biochemical milieu of eggshell membranes (ESM) were analyzed by using mass spectrometry techniques including matrix assisted laser desorption ionization ...


Role Of Vav2 In Podocyte Inflammasome Activation And Glomerular Injury During Hyperhomocysteinemia, Sabena Conley Jan 2016

Role Of Vav2 In Podocyte Inflammasome Activation And Glomerular Injury During Hyperhomocysteinemia, Sabena Conley

Theses and Dissertations

Hyperhomocysteinemia (hHcys) is a widely known pathogenic factor in the progression of end-stage renal disease (ESRD) and it is also associated with an increased risk for injurious cardiovascular pathologies during ESRD. HHcys is linked to the formation and activation of the NOD-like receptor protein 3 (NLRP3) inflammasome, characterized as a critical early mechanism initiating the inflammatory response. NADPH oxidase (NOX)-derived reactive oxygen species (ROS) mediate the activation of the NLRP3 inflammasome in podocytes in response to elevated levels of homocysteine (Hcys) in vitro and in vivo. However, it remains unknown how NLRP3 inflammasome activation is triggered by NOX. The ...


Functional Consequences Of Ama1-Ron2 Interaction During Host Cell Invasion By Toxoplasma., Shruthi Krishnamurthy Jan 2016

Functional Consequences Of Ama1-Ron2 Interaction During Host Cell Invasion By Toxoplasma., Shruthi Krishnamurthy

Graduate College Dissertations and Theses

T.gondii is a model organism of the phylum Apicomplexa that infects one third of the human population. While the majority of infections are asymptomatic or manifest with mild flu-like symptoms, toxoplasmosis can be fatal in immunocompromised individuals and in the developing fetus. The lytic cycle of tachyzoite-stage parasites causes damage to the host by repeated rounds of host cell invasion, intracellular replication and lysis of the host cell upon egress.

Invasion is a key step for the parasite to maintain its intracellular lifestyle. Apical Membrane Antigen 1 (AMA1) is an adhesin released from a unique set of secretory organelles ...