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Medicine and Health Sciences

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Full-Text Articles in Molecular Biology

Characterizing Aft1/2-Grx3/4 Interaction And The Role Of Bol2 During Iron Regulation In Saccharomyces Cerevisiae, William Rivers Apr 2019

Characterizing Aft1/2-Grx3/4 Interaction And The Role Of Bol2 During Iron Regulation In Saccharomyces Cerevisiae, William Rivers

Senior Theses

Iron dysregulation has been linked to a variety of human diseases, such as anemia, Friedreich’s ataxia, X-linked sideroblastic anemia, sideroblastic-like microcytic anemia, and myopathy. Thus, it is vitally important to understand the mechanisms for regulating intracellular iron. Here, we use fluorescence microscopy techniques in live cells to study interactions of the yeast proteins Grx3/4, Aft1/2, and Bol2, which have been shown to be involved in turning off iron import when the cell has adequate iron. Modified versions of genes encoding these proteins have been incorporated into several yeast backgrounds to use fluorescence to monitor interactions under varying ...


Regulation Of The Long Non-Coding Rna Fam83h-As1 By Human Papillomavirus In Cervical Cancer, Jamie Ann Barr Ph.D. Jan 2019

Regulation Of The Long Non-Coding Rna Fam83h-As1 By Human Papillomavirus In Cervical Cancer, Jamie Ann Barr Ph.D.

Graduate Theses, Dissertations, and Problem Reports

Non-coding RNAs (NcRNAs), such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been found to be involved in a variety of critical biological processes, and dysregulation of ncRNAs have been involved with several human diseases including cancer.

High-risk human papillomavirus (HPV) infection is one of the first events in the process of carcinogenesis in cervical and a subset of head and neck cancers. The expression of the viral oncoproteins E6 and E7 is essential in this process by inactivating the tumor suppressor proteins p53 and Rb, respectively, in addition to their interactions with other host proteins and regulation of ...


Nanoscale Stiffness Cues Influence Valvular Interstitial Cell Activation To Myofibroblasts, Michaela Wenning Jan 2019

Nanoscale Stiffness Cues Influence Valvular Interstitial Cell Activation To Myofibroblasts, Michaela Wenning

Undergraduate Honors Theses

Surgery is currently the primary treatment option for aortic valve stenosis (AVS) patients, many of whom are ineligible for surgery and are left untreated. AVS is progression is known to differ between males and females, and an understanding of sex-specific mechanisms of disease progression is imperative in developing accurate treatment options for men and women. The development of a nonsurgical therapy for AVS patients requires a deeper understanding of the molecular and cellular mechanisms of AVS progression. Currently, the role of calcium phosphate nanoparticles detected in the aortic valve during early stages of AVS in influencing disease progression and valvular ...


Comparative Analysis Of Dna Isolation Methods For The Human Microbiome, Hannah Chatwin Jan 2019

Comparative Analysis Of Dna Isolation Methods For The Human Microbiome, Hannah Chatwin

Undergraduate Honors Theses

The human microbiome is made up of millions of microbes coexisting in and on us with involvement in health and disease. The exact mechanisms by which this occurs have yet to be fully elucidated. Due to high variability in the composition of each person’s microbiome, it requires large numbers of people to begin to identify some of these processes. A major road block to generating large data sets for analysis is the high cost of DNA isolation from large collections of phenotypically well-characterized human subjects. This study explores the possible application of an inexpensive alternative DNA isolation method utilizing ...


Further Characterization Of The Skeletal Phenotype In A Hurler Syndrome Mouse Model And The Ethical Treatment Of Children In Medicine, Anna Marie Mcwoods Jan 2019

Further Characterization Of The Skeletal Phenotype In A Hurler Syndrome Mouse Model And The Ethical Treatment Of Children In Medicine, Anna Marie Mcwoods

MSU Graduate Theses

Mucopolysaccharidosis type I (MPS I) is a rare, autosomal recessive disorder caused by the deficiency of the lysosomal enzyme α-L-iduronidase (IDUA). Absence of IDUA results in the accumulation of dermatan and heparin sulfate and ultimately causes multi-system dysfunction. The most severe form of MPS I is Hurlers syndrome, a rapidly progressive disorder that, if left untreated, is fatal. Current treatment options for diagnosed individuals includes hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT). These treatments are able to ameliorate the majority of symptoms with the exception of the bone phenotype. This investigation aimed to further characterize the bone ...


Virulence Regulation In Pseudomonas Aeruginosa Via The Alginate Regulators, Algu And Algr, The Posttranscriptional Regulator, Rsma, And The Two-Component System, Algz/R, Sean Stacey Dec 2018

Virulence Regulation In Pseudomonas Aeruginosa Via The Alginate Regulators, Algu And Algr, The Posttranscriptional Regulator, Rsma, And The Two-Component System, Algz/R, Sean Stacey

Electronic Theses and Dissertations

Pseudomonas aeruginosa is a Gram-negative bacillus able to colonize a wide variety of environments. In the human host, P. aeruginosa can establish an acute infection or persist and create a chronic infection. P. aeruginosa is able to establish a niche and persist in human hosts by using a wide array of virulence factors used for: movement, killing host cells, and evading immune cells and antibiotics. Understanding virulence factors and their regulation has proved to be an important means of combating the morbidity and mortality of P. aeruginosa as well as the ever-increasing threat of drug resistance. By targeting virulence factors ...


The N-Terminal Methyltransferase Homologs Nrmt1 And Nrmt2 Exhibit Novel Regulation Of Activity Through Heterotrimer Formation., Jon David Faughn Aug 2018

The N-Terminal Methyltransferase Homologs Nrmt1 And Nrmt2 Exhibit Novel Regulation Of Activity Through Heterotrimer Formation., Jon David Faughn

Electronic Theses and Dissertations

Protein, DNA, and RNA methyltransferases have an ever-expanding list of novel substrates and catalytic activities. Even within families and between homologs, it is becoming clear the intricacies of methyltransferase specificity and regulation are far more diverse than originally thought. In addition to specific substrates and distinct methylation levels, methyltransferase activity can be altered through formation of complexes with close homologs. This work involves the N-terminal methyltransferase homologs NRMT1 and NRMT2. NRMT1 is a ubiquitously expressed distributive trimethylase. NRMT2 is a monomethylase expressed at low levels and in a tissue-specific manner. They are both nuclear methyltransferases with overlapping target consensus sequences ...


Deciphering The Role Of Human Arylamine N-Acetyltransferase 1 (Nat1) In Breast Cancer Cell Metabolism Using A Systems Biology Approach., Samantha Marie Carlisle Aug 2018

Deciphering The Role Of Human Arylamine N-Acetyltransferase 1 (Nat1) In Breast Cancer Cell Metabolism Using A Systems Biology Approach., Samantha Marie Carlisle

Electronic Theses and Dissertations

Background: Human arylamine N-acetyltransferase 1 (NAT1) is a phase II xenobiotic metabolizing enzyme found in almost all tissues. NAT1 can additionally hydrolyze acetyl-coenzyme A (acetyl-CoA) in the absence of an arylamine substrate. NAT1 expression varies inter-individually and is elevated in several cancers including estrogen receptor positive (ER+) breast cancers. Additionally, multiple studies have shown the knockdown of NAT1, by both small molecule inhibition and siRNA methods, in breast cancer cells leads to decreased invasive ability and proliferation and decreased anchorage-independent colony formation. However, the exact mechanism by which NAT1 expression affects cancer risk and progression remains unclear. Additionally, consequences ...


Bayesian Analytical Approaches For Metabolomics : A Novel Method For Molecular Structure-Informed Metabolite Interaction Modeling, A Novel Diagnostic Model For Differentiating Myocardial Infarction Type, And Approaches For Compound Identification Given Mass Spectrometry Data., Patrick J. Trainor Aug 2018

Bayesian Analytical Approaches For Metabolomics : A Novel Method For Molecular Structure-Informed Metabolite Interaction Modeling, A Novel Diagnostic Model For Differentiating Myocardial Infarction Type, And Approaches For Compound Identification Given Mass Spectrometry Data., Patrick J. Trainor

Electronic Theses and Dissertations

Metabolomics, the study of small molecules in biological systems, has enjoyed great success in enabling researchers to examine disease-associated metabolic dysregulation and has been utilized for the discovery biomarkers of disease and phenotypic states. In spite of recent technological advances in the analytical platforms utilized in metabolomics and the proliferation of tools for the analysis of metabolomics data, significant challenges in metabolomics data analyses remain. In this dissertation, we present three of these challenges and Bayesian methodological solutions for each. In the first part we develop a new methodology to serve a basis for making higher order inferences in metabolomics ...


Regulation Of The Pi3-Kinase/Pten Signaling Pathway By Tgf-Β In Prostate Cancer Cells, Mawiyah Kimbrough-Allah May 2018

Regulation Of The Pi3-Kinase/Pten Signaling Pathway By Tgf-Β In Prostate Cancer Cells, Mawiyah Kimbrough-Allah

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

Transforming growth factor -β (TGF-β) plays an important role in the progression of prostate cancer. It acts as a tumor suppressor in normal epithelial cells but as a tumor promoter in advanced prostate cancer cells. The PI3-kinase pathway has been shown to play integral roles in many cellular processes including cell proliferation, survival, and cell migration in many cell types. PI3-kinase pathway mediates TGF-β effects on prostate cancer cell migration and invasion. Phosphatase and tensin homolog (PTEN), a tumor suppressor gene, inhibits PI3-kinase pathway and is frequently mutated in prostate cancers. In this present study, we investigated possible roles of ...


Development Of Lc-Ms For The Identification And Characterization Of Non-Adjacent Dna Photoproduct Formation In G-Quadruplex Forming Sequences, Claudia Posadas May 2018

Development Of Lc-Ms For The Identification And Characterization Of Non-Adjacent Dna Photoproduct Formation In G-Quadruplex Forming Sequences, Claudia Posadas

Arts & Sciences Electronic Theses and Dissertations

Ultraviolet light is well known to induce cyclobutane pyrimidine dimers (CPD) and pyrimidine (6–4) pyrimidone photoproducts in duplex DNA, which interfere with DNA replication and transcription. Recently, a new class of DNA photoproducts known as anti cyclobutanepyrimidine dimers have been discovered, which form in G-quadruplex forming sequences in solution. G-quadruplex structures have been proposed to form in human DNA telomeres and certain promoters in vivo but evidence for their existence has been lacking. Since anti-cyclobutante pyrimidine dimers have been shown to form in G-quadruplex forming sequences, their formation in irradiated human cells could be used to confirm the ...


Melatonin-Micronutrients Osteopenia Treatment Study (Mots): A Translational Study Assessing The Effects Of Melatonin, Strontium Citrate, Vitamin D3 And Vitamin K2 On Bone Density, Bone Turnover Markers And Health-Related Quality Of Life In Postmenopausal Osteopenic Women Following A One-Year Double-Blind Randomized Placebo-Controlled Trial And On Osteoblast-Osteoclast Co-Cultures, Sifat Maria May 2018

Melatonin-Micronutrients Osteopenia Treatment Study (Mots): A Translational Study Assessing The Effects Of Melatonin, Strontium Citrate, Vitamin D3 And Vitamin K2 On Bone Density, Bone Turnover Markers And Health-Related Quality Of Life In Postmenopausal Osteopenic Women Following A One-Year Double-Blind Randomized Placebo-Controlled Trial And On Osteoblast-Osteoclast Co-Cultures, Sifat Maria

Electronic Theses and Dissertations

Objective: The purpose of this study was to assess if a novel combination of melatonin and three other natural bone-aiding micronutrients: strontium citrate, vitamins D3 and K2 (MSDK) could improve bone health by modulating the activity of osteoblasts and osteoclasts in favor of balanced bone remodeling and by improving the overall health-related quality of life in postmenopausal osteopenic women.

Methods: The Melatonin-micronutrients Osteopenia Treatment Study (MOTS) is a translational research study that used both clinical and in vitro approaches to assess the efficacy of MSDK on bone health in women and to identify potential mechanisms for its effects ...


Muc4 Based Immunotherapy For Pancreatic Cancer, Kasturi Banerjee May 2018

Muc4 Based Immunotherapy For Pancreatic Cancer, Kasturi Banerjee

Theses & Dissertations

Pancreatic Cancer (PC) is a lethal disease claiming approximately 45000 lives in the US in 2018, and it establishes an elaborate immunosuppressive tumor microenvironment that aids in disease pathogenesis. Immunotherapy has emerged as a strategy to target tumor cells by reprogramming patient’s immune system. Challenges present in PC immunotherapy are: i) identifying a tumor-associated antigen that could be targeted, ii) identifying adjuvants that could efficiently deliver antigens, iii) eliciting robust anti-tumor responses and iv) overcoming peripheral tolerance and immunosuppression elicited by the tumor.

Firstly, we detected circulating autoantibodies to MUC4 present in PC patients and observed that IgM autoantibodies ...


The Regulation Of Dna Methylation In Mammalian Development And Cancer, Nicolas Veland May 2018

The Regulation Of Dna Methylation In Mammalian Development And Cancer, Nicolas Veland

UT GSBS Dissertations and Theses (Open Access)

DNA methylation is an essential epigenetic modification in mammals, as it plays important regulatory roles in multiple biological processes, such as gene transcription, maintenance of chromosomal structure and genomic stability, genomic imprinting, retrotransposon silencing, and X-chromosome inactivation. Dysregulation of DNA methylation is associated with various human diseases. For example, cancer cells usually show global hypomethylation and regional hypermenthylation, which have been implicated in genomic instability and tumor suppressor silencing, respectively. Although great progress has been made in elucidating the biological functions of DNA methylation over the last several decades, how DNA methylation patterns and levels are regulated and dysregulated is ...


Nanoscale Organization Of The Small Gtpase Rac1, Kelsey Maxwell May 2018

Nanoscale Organization Of The Small Gtpase Rac1, Kelsey Maxwell

UT GSBS Dissertations and Theses (Open Access)

Rac1 is a small, guanine-nucleotide binding protein that cycles between an inactive GDP-bound and active GTP-bound state to regulate actin-mediated motility, migration, and adhesion. Plasma membrane (PM) localization is essential for its biological activity. Rac1 PM targeting is directed by a C-terminal membrane anchor that encompasses a geranylgeranyl-cysteine-methyl-ester, palmitoyl, and a polybasic domain (PBD) of contiguous lysine and arginine residues. Using high-resolution imaging combined with spatial mapping analysis, I found that Rac1 forms nanoclusters on the PM. Cycling between the GTP- and GDP-bound states, Rac1 forms nanoclusters that are non-overlapping, consequently undergoing guanine nucleotide-dependent spatial segregation. I further found that ...


Investigating The Impact Of Intragenic Dna Methylation On Gene Expression, And The Clinical Implications On Tumor Cells And Associated Stroma, Michael Mcguire May 2018

Investigating The Impact Of Intragenic Dna Methylation On Gene Expression, And The Clinical Implications On Tumor Cells And Associated Stroma, Michael Mcguire

UT GSBS Dissertations and Theses (Open Access)

Investigations into the function of non-promoter DNA methylation have yielded new insights into epigenetic regulation of gene expression. Previous studies have highlighted the importance of distinguishing between DNA methylation in discrete functional regions; however, integrated non-promoter DNA methylation and gene expression analyses across a wide number of tumor types and corresponding normal tissues have not been performed. Through integrated analysis of gene expression and DNA methylation profiles, we uncovered an enrichment of DNA methylation sites within the gene body and 3’UTR in which DNA methylation is strongly positively correlated with gene expression. We examined 32 tumor types and identified ...


Characterization Of The Roles Of Muscle-Synthesized Brain-Derived Neurotrophic Factor And Presynaptic Tyrosine Receptor Kinase B In Motor Neuron Axonal Transport, Luke A. Vanosdol Mar 2018

Characterization Of The Roles Of Muscle-Synthesized Brain-Derived Neurotrophic Factor And Presynaptic Tyrosine Receptor Kinase B In Motor Neuron Axonal Transport, Luke A. Vanosdol

All NMU Master's Theses

Brain-derived neurotrophic factor (BDNF) is a small, diffusible protein essential for the development and function of neurons. It is synthesized by many types of tissue, including muscle. BDNF actions are mediated via binding to its receptor, tyrosine receptor kinase B (TrkB). The BDNF-TrkB complex is endocytosed into a specialized vesicle, which induces downstream signaling cascades locally in the dendrites, or, more often, is delivered to the cell soma via retrograde axonal transport, where it modulates gene expression. BDNF activation of TrkB is critical for the initiation of axonal transport, and this cellular process relies on the interaction of numerous adaptor ...


Functional And Structural Mimicry Of A-Kinase Anchoring Proteins By Human Adenovirus E1a, Cason R. King Feb 2018

Functional And Structural Mimicry Of A-Kinase Anchoring Proteins By Human Adenovirus E1a, Cason R. King

Electronic Thesis and Dissertation Repository

As an obligate intracellular parasite, human adenovirus (HAdV) must utilize host factors for survival and replication. Early during infection, its multifunctional E1A protein interacts with an impressive range of cellular target proteins to exert control over the cellular environment. Through these virus-host interactions, E1A massively reprograms both viral and cellular transcription to activate the other HAdV genes, downregulate the host’s immune response, and induce the cell cycle. Consequently, E1A converts the infected cell into a compliant state more amenable for HAdV replication, resulting from its numerous protein-protein interactions. I sought to examine E1A’s interaction with cellular protein kinase ...


Wnt5a Signaling Induced Phosphorylation Increases Acyl Protein Thioesterase Activity And Promotes Melanoma Metastatic Behavior, Rochelle Shirin Sadeghi Jan 2018

Wnt5a Signaling Induced Phosphorylation Increases Acyl Protein Thioesterase Activity And Promotes Melanoma Metastatic Behavior, Rochelle Shirin Sadeghi

Publicly Accessible Penn Dissertations

Wnt5a has been implicated in melanoma progression and metastasis, although the exact downstream signaling events that contribute to melanoma metastasis are poorly understood. Wnt5a signaling results in acyl protein thioesterase 1 (APT1) mediated depalmitoylation of pro-metastatic cell adhesion molecules CD44 and MCAM, resulting in increased melanoma invasion. The mechanistic details that underlie Wnt5a-mediated regulation of APT1 activity and cellular function remains unknown. Here, we show Wnt5a signaling regulates APT1 activity through induction of APT1 phosphorylation and we further investigate the functional role of APT1 phosphorylation on its depalmitoylating activity. We found phosphorylation increased APT1 depalmitoylating activity and reduced APT1 dimerization ...


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 ...


Studies Of Norspermidine Uptake In Drosophila Suggest The Existence Of Multiple Polyamine Transport Pathways, Michael Dieffenbach Jan 2018

Studies Of Norspermidine Uptake In Drosophila Suggest The Existence Of Multiple Polyamine Transport Pathways, Michael Dieffenbach

Honors Undergraduate Theses

Polyamines are a class of essential nutrients involved in many basic cellular processes such as gene expression, cell proliferation, and apoptosis. Without polyamines, cell growth is delayed or halted. Cancerous cells require an abundance of polyamines through a combination of synthesis and transport from the extracellular environment. An FDA-approved drug, D,L-α-difluoromethylornithine (DFMO), blocks polyamine synthesis but is ineffective at inhibiting cell growth due to polyamine transport. Thus, there is a need to develop drugs that inhibit polyamine transport to use in combination with DFMO. Surprisingly, little is known about the polyamine transport system in humans and other eukaryotes. Understanding ...


Comparison And Evaluation Of Two Rapid Diagnostic Assays For The Identification Of Mycoplasma Species, Aric James Mcdaniel Jan 2018

Comparison And Evaluation Of Two Rapid Diagnostic Assays For The Identification Of Mycoplasma Species, Aric James Mcdaniel

Graduate Theses and Dissertations

Members of the class Mollicutes are unique among bacteria in that they are unable to synthesize a cell wall. These organisms are also difficult to culture and very slow-growing with some species requiring up to 40 days to culture. Many of these bacteria are also significant pathogens in humans and animals, so rapid identification of isolates is a necessary diagnostic step. Many different tests are used for identification of pathogenic Mollicutes (primarily Mycoplasma and Ureaplasma species), however most tests are not cost or time efficient. Two relatively recent diagnostic tools are matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry and ...


Wnt Secretion Proteins Modulate Rankl-Induced Expression Of Aire In Thymic Epithelial Cells, Daniel Pollack Jan 2018

Wnt Secretion Proteins Modulate Rankl-Induced Expression Of Aire In Thymic Epithelial Cells, Daniel Pollack

Dissertations and Theses

Thymic epithelial cells (TEC) are essential for a proper adaptive immune response by regulating thymocyte development and establishing central tolerance. In the thymus, TECs differentially express Wnt proteins, which activate canonical and non-canonical Wnt signaling pathways. Wnt signaling is thought to regulate cell survival, proliferation, and development although the direct molecular mechanisms in TECs have yet to be elucidated. The inducible inhibition of canonical Wnt signaling with Dkk1 leads to a rapid loss of TEC progenitors as well as a decline in mature Aire-expressing mTECs. Therefore, we explore the role of Wnt ligands potentially responsible for stimulating and/or regulating ...


Identification Of Factors Involved In 18s Nonfunctional Ribosomal Rna Decay And A Method For Detecting 8-Oxoguanosine By Rna-Seq, Kelly A. Limoncelli Dec 2017

Identification Of Factors Involved In 18s Nonfunctional Ribosomal Rna Decay And A Method For Detecting 8-Oxoguanosine By Rna-Seq, Kelly A. Limoncelli

GSBS Dissertations and Theses

The translation of mRNA into functional proteins is essential for all life. In eukaryotes, aberrant RNAs containing sequence features that stall or severely slow down ribosomes are subject to translation-dependent quality control. Targets include mRNAs encoding a strong secondary structure (No-Go Decay; NGD) or stretches of positively-charged amino acids (Peptide-dependent Translation Arrest/Ribosome Quality Control; PDTA/RQC), mRNAs lacking an in-frame stop codon (Non-Stop Decay; NSD), or defective 18S rRNAs (18S Nonfunctional rRNA Decay; 18S NRD). Previous work from our lab showed that the S. cerevisiae NGD factors DOM34 and HBS1, and PDTA/RQC factor ASC1, all participate in the ...


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 ...


The Functions Of Setd5 And Mir-221 In Embryonic Stem Cell Differentiation, Tsai-Yu Chen Dec 2017

The Functions Of Setd5 And Mir-221 In Embryonic Stem Cell Differentiation, Tsai-Yu Chen

UT GSBS Dissertations and Theses (Open Access)

Embryonic stem cells (ESCs) are a widely used model system to study cellular differentiation because of their pluripotent characteristics, and ESC differentiation is an epigenetic process. In an effort to identify a new epigenetic factor that is required for ESC differentiation, the function of SETD5 in ESCs was studied for this thesis. Results show that SETD5 is essential for retinoic acid (RA)-induced differentiation of mouse ESCs and for RA-induced expression of critical developmental genes (e.g., Hoxa1 and Hoxa2) and neuron-related genes (e.g., Nestin and Pax6). SETD5 was upregulated during ESC differentiation. Additional results demonstrated that SETD5 bound ...


Insights Into The Therapeutic Potential Of Salt Inducible Kinase 1: A Novel Mechanism Of Metabolic Control, Randi Fitzgibbon Dec 2017

Insights Into The Therapeutic Potential Of Salt Inducible Kinase 1: A Novel Mechanism Of Metabolic Control, Randi Fitzgibbon

UT GSBS Dissertations and Theses (Open Access)

Salt inducible kinase 1 (SIK1) has been considered a stress-inducible kinase since it was first cloned in 1999. Continued efforts since this time have been dedicated to characterizing the structure and function of SIK1. Such research has laid the ground work for our understanding of SIK1 action and regulation in tissue and stimuli dependent manners. The fundamental findings of this dissertation continue in this tradition and include investigations of SIK1 regulatory mechanisms in skeletal muscle cells, the cellular and physiological effects of SIK1 loss of function in vitro and in vivo, and intracellular metabolic and mitochondrial regulation by this kinase ...


Endocytic Trafficking Of The Amyloid Precursor Protein In Rat Cortical Neurons, Sahily Reyes Dec 2017

Endocytic Trafficking Of The Amyloid Precursor Protein In Rat Cortical Neurons, Sahily Reyes

UT GSBS Dissertations and Theses (Open Access)

Amyloid-beta (Aβ) aggregation and deposition into extracellular plaques is a hallmark of the most common forms of dementia, including Alzheimer’s disease. The Aβ-containing plaques result from pathogenic cleavage of amyloid precursor protein (APP) by secretases resulting in intracellular production of Aβ peptides that are secreted and accumulate extracellularly. Despite considerable progress towards understanding APP processing and Aβ aggregation, the mechanisms underlying endosomal production of Aβ peptides and their secretion remain unclear. Using endosomes isolated from cultured primary neurons, we determined that the trafficking of APP from the endosomal membrane into internal vesicles of late endosome/multivesicular bodies (MVB) is ...


Developing Algorithms For Quantifying The Super Resolution Microscopic Data: Applications To The Quantification Of Protein-Reorganization In Bacteria Responding To Treatment By Silver Ions, Sai Divya Challapalli Dec 2017

Developing Algorithms For Quantifying The Super Resolution Microscopic Data: Applications To The Quantification Of Protein-Reorganization In Bacteria Responding To Treatment By Silver Ions, Sai Divya Challapalli

Theses and Dissertations

Histone-like nucleoid structuring proteins (HNS) play significant roles in shaping the chromosomal DNA, regulation of transcriptional networks in microbes, as well as bacterial responses to environmental changes such as temperature fluctuations. In this work, the intracellular organization of HNS proteins in E. coli bacteria was investigated utilizing super-resolution fluorescence microscopy, which surpasses conventional microscopy by 10–20 fold in spatial resolution. More importantly, the changes of the spatial distribution of HNS proteins in E. coli, by addition of silver ions into the growth medium were explored. To quantify the spatial distribution of HNS in bacteria and its changes, an automatic ...