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Age-Dependent Breakdown Of The Blood Brain Barrier And Associated Changes In S100b Ko Mice, Eric V. Brown 2015 Rowan University

Age-Dependent Breakdown Of The Blood Brain Barrier And Associated Changes In S100b Ko Mice, Eric V. Brown

Graduate School of Biomedical Sciences Theses and Dissertations

Autoantibodies play an important role in many autoimmune diseases. Recent research has shown that breakdown of the blood brain barrier (BBB) occurs concomitant to generation of brain reactive autoantibodies in many neurodegenerative diseases, which serve as biomarkers and drivers of pathology. SI00B, a calcium binding protein found most highly expressed in astrocytes which ensheathe the BBB, has many functions in neural development and signaling. Currently literature indicates that S100B KO mice develop normally, with no phenotypic abnormalities. Here, it is demonstrated that S100B KO mice seem to develop a chronic BBB breakdown similar to that seen in human neurodegenerative diseases. …


Hearing Sensitivity And The Effect Of Sound Exposure On The Axolotl (Ambystoma Mexicanum), Amy K. Fehrenbach 2015 Western Kentucky University

Hearing Sensitivity And The Effect Of Sound Exposure On The Axolotl (Ambystoma Mexicanum), Amy K. Fehrenbach

Masters Theses & Specialist Projects

The axolotl (Ambystoma mexicanum) has been used as a model organism for studying development, genetics, and regeneration. Although the sensory hair cells of the lateral line of this species have been shown to be able to regenerate, it is not known whether this also occurs in the inner ear. In fact, little is known about the hearing capabilities of the axolotl or other salamander species. I recorded auditory evoked potentials (AEPs) of six axolotls at eleven frequencies (0.1, 0.25, 0.4, 0.6, 0.8, 1, 1.5, 2, 3, 4, and 6 kHz) in order to produce baseline audiograms of underwater pressure sensitivity. …


Radium-223 For The Treatment Of Castration-Resistant Prostate Cancer, Joelle El-Amm, Jeanny B. Aragon-Ching 2015 George Washington University

Radium-223 For The Treatment Of Castration-Resistant Prostate Cancer, Joelle El-Amm, Jeanny B. Aragon-Ching

Medicine Faculty Publications

The vast majority of patients with metastatic castration-resistant prostate cancer (mCRPC) develop bone metastases. Bone metastases are a source of significant morbidity and affect quality of life in these patients. Several bone-targeting agents are approved for the treatment of bone metastases in prostate cancer, including bisphosphonates, denosumab, and radiopharmaceuticals. Radium-223 is a novel first-in-class alpha-emitting radiopharmaceutical that has been approved for treatment of patients with mCRPC with bone metastases. Radium-223 delivers cytotoxic radiation to the sites of bone metastases and offers the advantage of minimal myelosuppression. The landmark Phase III ALSYMPCA trial demonstrated that, in addition to providing bone-related palliation, …


Development Of Quantitative Tools For The Characterization And Analysis Of The Blood Brain Barrier In Normal And Mps Iiib Mice, Sara M. Rigney 2015 Dominican University of California

Development Of Quantitative Tools For The Characterization And Analysis Of The Blood Brain Barrier In Normal And Mps Iiib Mice, Sara M. Rigney

Dissertations, Masters Theses, Capstones, and Culminating Projects

The Blood Brain Barrier (BBB) functions to control homeostasis within the central nervous system (CNS) via strict control over the passage of molecules into and out of the brain. The goal of this barrier is to protect the CNS from harmful external factors while allowing entry of essential nutrients and removal of metabolic byproducts. This restrictive nature of the BBB is due to the protein network at the borders of adjoining cerebral endothelial cells known as the tight junctions (TJs) and the relationship of other supporting cells and proteins such as astrocytes, pericytes, microglia, and the basement membrane and extracellular …


Discovering The Sequence Specificity Of Human Dyrk2 And Dyrk4, Julie Klaric 2015 University of Connecticut - Storrs

Discovering The Sequence Specificity Of Human Dyrk2 And Dyrk4, Julie Klaric

University Scholar Projects

Protein phosphorylation is a post-translational modification (PTM) that is ubiquitous in regulating cellular processes. It is the most common PTM used in signal translation. Protein kinases are the class of enzymes that catalyze the transfer of a phosphate group from ATP to a specific amino acid on a substrate protein. In eukaryotes, kinases generally add a phosphate to serine, threonine, or tyrosine residues. Short linear patterns in the amino acid sequence of the substrate protein help guide the protein kinase to the correct residue to be phosphorylated. However, these patterns, or “motifs,” as well as the complete list of substrates …


Characterization Of A Novel Clade Of Transporters In Phytophthora, Stephanie Padula, Paul F. Morris Dr, Howard Casey Cromwell Dr., Menaka Ariyaratne, Andrew Wagner 2015 Bowling Green State University

Characterization Of A Novel Clade Of Transporters In Phytophthora, Stephanie Padula, Paul F. Morris Dr, Howard Casey Cromwell Dr., Menaka Ariyaratne, Andrew Wagner

Honors Projects

The oomycete Phytophthora parasitica has a worldwide distribution and is an economically important pathogen of more than 100 species4. RNA-seq analysis showed that one gene, PPTG_16698 has the 5th highest level of expression of all transport proteins in the zoospore stage, and is highly conserved throughout Phytophthora species. This project attempts to characterize the important biological role that PPTG_16698 plays in P. parasitica and other oomycetes. Three strategies have been implemented to accomplish this goal: growth analysis by heterologous expression in yeast, metabolite analysis in yeast, and construction of a GFP fusion protein to enable localization of …


Growth Of Breast Tumors In Vitro To Characterize A Terahertz Imaging Platform, Scarlett-Marie Acklin 2015 University of Arkansas, Fayetteville

Growth Of Breast Tumors In Vitro To Characterize A Terahertz Imaging Platform, Scarlett-Marie Acklin

Biological Sciences Undergraduate Honors Theses

In this research, different methods were investigated to grow in-vitro breast cancer tumors embedded in gel using the 4T1 cell line. The goal of this research was to test a new medical imaging modality available at the University of Arkansas using terahertz (THz) waves. The THz imaging and spectroscopy system has shown capability of high-resolution imaging and characterization of human breast tumors fixed in formalin and embedded in paraffin. In order to further examine this new imaging system in a laboratory environment, attempts to grow breast tumors in-vitro were conducted. Results were produced in two different environments, flat-bottomed plates and …


Efficient In Vitro Development Of Photoreceptors From Human Pluripotent Stem Cells, Joseph C. Reynolds 2015 Dominican University of California

Efficient In Vitro Development Of Photoreceptors From Human Pluripotent Stem Cells, Joseph C. Reynolds

Dissertations, Masters Theses, Capstones, and Culminating Projects

Degeneration of the rod and cone photoreceptors in the human retina is among the most common causes of blindness. Replacing these damaged photoreceptors may help to restore vision. Repairing the damaged retina relies on the insertion of new, healthy cells. Embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are two possible sources of photoreceptors to restore vision. Previous data shows that human ES cells and iPS cells can be differentiated into photoreceptors and transplanted into the eye to restore some vision. However, this process is inefficient, and costly. Here, we show a new method for inducing photoreceptor production …


Progressive Decline Of Testicular Function In Leptinreceptor Deficient Obese Mice, Jennifer Long 2015 Western Michigan University

Progressive Decline Of Testicular Function In Leptinreceptor Deficient Obese Mice, Jennifer Long

Masters Theses

The incidence of obesity and metabolic syndrome among the human population is increasing, but the effects on male fertility are unresolved. Leptin insensitivity appears to show a consistent relationship between obesity and fertility problems in men. Genetically modified mice lacking the leptin hormone (ob/ob) or leptin receptor (db/db) are reported to be subfertile and/or infertile but there is only minimal information about testicular function (sperm and hormone production) and the progression of infertility. Therefore, this study was designed to investigate testicular function using a leptin-receptor-deficient obese mouse model (the POUND mouse; Charles River). Testicular sperm production is reduced in POUND …


The Effect Of High Terperature On Mating: Developmental Buffering Of S. Cerevisiae To The Environment, Sarah Hosie 2015 Syracuse University

The Effect Of High Terperature On Mating: Developmental Buffering Of S. Cerevisiae To The Environment, Sarah Hosie

Renée Crown University Honors Thesis Projects - All

In Saccharomyces cerevisiae, cellular polarization is an essential structural and functional aspect of growth and development. It is responsible for yielding and maintaining cellular asymmetry, and allows for cells to function. Mating in S. cerevisiae is a process that incorporates cell-to-cell signaling, signal transduction, cellular polarization, plasmogamy, karyogamy, and many other cellular processes. Each of these steps is mediated by a myriad of signaling proteins that are involved in a signaling cascade that is regulated by both extracellular and intracellular signals. Much is known about the mating process and pathway in S. cerevisiae. However, this project aimed to …


Overexpression And Gene Profiling Of Asparagine Synthetase In Hybrid Poplar, Kristopher Murray 2015 Syracuse University

Overexpression And Gene Profiling Of Asparagine Synthetase In Hybrid Poplar, Kristopher Murray

Renée Crown University Honors Thesis Projects - All

Plants with polysaccharide-rich secondary cell walls have great potential as a source of carbohydrates for bioethanol production. However, the presence of phenolic lignin inhibits the isolation of bioethanol precursors cellulose and hemicellulose from the secondary cell wall. Recent studies have linked nitrogen availability to secondary cell wall development and composition, making nitrogen metabolism genes an interesting target in the improvement of plant cell walls for biofuels production. Plants use a nitrogen assimilation pathway to convert inorganic nitrogen sources into organic sources, included amino acids, which play key roles in metabolism and cell wall development. Asparagine synthetase (AS), a key enzyme …


Characterization Of Ghrelin O-Acyltransferase Active Site, Leslie Patton 2015 Syracuse University

Characterization Of Ghrelin O-Acyltransferase Active Site, Leslie Patton

Renée Crown University Honors Thesis Projects - All

Ghrelin, first discovered in 1999, is a 28-amino acid peptide hormone involved in the regulation of appetite, insulin secretion and sensitivity, and many neurological effects such as learning, memory, and depression.1-6 Ghrelin has been identified to have a unique posttranslational octanoylation carried out by the enzyme ghrelin O-acyltransferase (GOAT). This distinctive modification is a point of interest in studying GOAT whereby blocking the acylation of the ghrelin could potentially halt the activity of the peptide hormone and provide a means of treating obesity, diabetes, and other diseases affected by ghrelin levels. The duration of my project involved working …


Role Of Ribosomal Biogenesis In Axonal Morphogenesis., Nicholas McChesney Lynch 2015 University of Louisville

Role Of Ribosomal Biogenesis In Axonal Morphogenesis., Nicholas Mcchesney Lynch

College of Arts & Sciences Senior Theses

Elongating axons require a host of macromolecules for outgrowth. The importance of lipid, protein, and general RNA synthesis for initial axonal growth has been previously investigated, but the role of rRNA synthesis and ribosome production in axonal morphogenesis remains unclear. Therefore, rat hippocampal neurons were cultured and transfected with shRNA against either TIF-IA (the activator of RNA polymerase I) or RPS6 (a small ribosomal subunit component) to determine the effects of impaired de novo ribosome synthesis on axonal development during the first three days after plating. Our data show that shRPS6 weakly inhibited total axon length, but not longest axon …


The Development Of Skeletal Muscle In Young Horses: An Ultrasonography And Satellite Cell Approach, Emma K. LaVigne 2015 University of Connecticut - Storrs

The Development Of Skeletal Muscle In Young Horses: An Ultrasonography And Satellite Cell Approach, Emma K. Lavigne

Honors Scholar Theses

Muscle growth in young horses is characterized by an increase in muscle cross-sectional area, which can be accomplished through the activation and differentiation of satellite cells. Satellite cells can be stimulated or inhibited in response to different cytokines and growth factors and are key mediators of muscle hypertrophy and regeneration. The aim of this study was to investigate the growth of the longissimus dorsi (LD) muscle in horses under 5 years of age and to obtain preliminary data on satellite cell behavior in foals. The area, width, height, and subcutaneous fat were measured using ultrasonography at 6-month increments over the …


Activation Of Nf-Κb Transcription Factor During In Vitro Differentiation Of Mouse Embryonic Stem Cells, Natalya A. Ortolano 2015 University of Southern Mississippi

Activation Of Nf-Κb Transcription Factor During In Vitro Differentiation Of Mouse Embryonic Stem Cells, Natalya A. Ortolano

Honors Theses

Embryonic stem cells (ESCs) are a promising cell source for regenerative medicine. However, recent studies indicated that ESCs and ESC-derived cells (ESC-DCs) lack functional innate immunity against various pathogens and inflammatory cytokines. This presents a barrier to clinical application, as ESC-DCs would be placed in a wound site and exposed to pathogens and inflammatory cytokines. Using mouse ESCs (mESCs) as a model, we recently demonstrated that they are deficient in expressing type I interferons (IFN) and inflammatory cytokines. To determine the molecular basis for this finding, this study examined the activation state of nuclear factor-κB (NF-κB), a transcription factor that …


The Hippo Pathway Effector Yki Downregulates Wg Signaling To Promote Retinal Differentiation In The Drosophila Eye, Erika Lynn Wittkorn, Ankita Sarkar, Kristine Garcia, Madhuri Kango-Singh, Amit Singh 2015 University of Dayton

The Hippo Pathway Effector Yki Downregulates Wg Signaling To Promote Retinal Differentiation In The Drosophila Eye, Erika Lynn Wittkorn, Ankita Sarkar, Kristine Garcia, Madhuri Kango-Singh, Amit Singh

Biology Faculty Publications

The evolutionarily conserved Hippo signaling pathway is known to regulate cell proliferation and maintain tissue homeostasis during development. We found that activation of Yorkie (Yki), the effector of the Hippo signaling pathway, causes separable effects on growth and differentiation of theDrosophila eye. We present evidence supporting a role for Yki in suppressing eye fate by downregulation of the core retinal determination genes. Other upstream regulators of the Hippo pathway mediate this effect of Yki on retinal differentiation. Here, we show that, in the developing eye, Yki can prevent retinal differentiation by blocking morphogenetic furrow (MF) progression and R8 specification. …


Impacts Of Micrornas On Skeletal Muscle Protein Synthesis And Mitochondrial Quality, David Lee 2015 University of Arkansas, Fayetteville

Impacts Of Micrornas On Skeletal Muscle Protein Synthesis And Mitochondrial Quality, David Lee

Graduate Theses and Dissertations

microRNA (miRNA) post-transcriptional modification is becoming a well-established mechanism for controlling mRNA translation. microRNAs -1, -133, and -206 are under the control of skeletal muscle promoters and affect muscle plasticity and metabolic health. A detailed review on the generation and processing of miRNAs with a view to skeletal muscle brings up intriguing connections in the transcriptional connections between multiple miRNAs. Additionally, exciting new research has defined a role of miRNAs in skeletal muscle mitochondria showing an additional, direct link to metabolic function. Multiple investigations in models of exercise, aging, hypertrophy, and injury have shown how these interventions can affect miRNA …


Induction Of Caspase-Dependent Death By Proteasome Targeted Therapy In Glioblastoma, Christa A. Manton 2015 The University of Texas Graduate School of Biomedical Sciences at Houston

Induction Of Caspase-Dependent Death By Proteasome Targeted Therapy In Glioblastoma, Christa A. Manton

Dissertations and Theses (Open Access)

New therapeutic options are needed for glioblastoma, a deadly disease with a median survival of only 14 months with current treatment. The proteasome inhibitor bortezomib (BTZ) shows efficacy in cancers like myeloma, but its clinical utility in other cancer types has been more limited. Newer proteasome inhibitors such as marizomib (MRZ) have unique inhibitory and death inducing properties that have not been well examined in GBM. Additionally, targeting other components of the ubiquitin-proteasome system is possible, but has not been explored in GBM. Questions also still remain about the ability of BTZ and MRZ to be delivered to brain tumors …


Manipulation Of The Microbiome And Its Impact On Functional Recovery Following Ischemic Stroke, Michal Jandzinski 2015 University of Connecticut

Manipulation Of The Microbiome And Its Impact On Functional Recovery Following Ischemic Stroke, Michal Jandzinski

Honors Scholar Theses

Each year, nearly 800,000 individuals residing in the United States will have a stroke. Of these, about 130,000 cases will prove fatal while many of the survivors will be forced to live with disability for the remainder of their lives. Out of all strokes over 87% are ischemic strokes. The widespread incidence of this debilitating condition costs the United States an estimated $36.5 billion dollars every single year. Despite this, clinicians are armed with very little to combat the disease. Recent research developments have brought about the rise in awareness about the importance of the microbiome, the various gut flora …


Igfbp2 Potentiates Egfr-Stat3 Signaling In Glioma, Yingxuan Chua 2015 The University of Texas Graduate School of Biomedical Sciences at Houston

Igfbp2 Potentiates Egfr-Stat3 Signaling In Glioma, Yingxuan Chua

Dissertations and Theses (Open Access)

Gliomas are clinically challenging brain tumors with dismal survival rates due to its infiltrative nature and ineffective standard therapy. Insulin-like growth factor binding protein 2 (IGFBP2) is a pleiotropic oncogenic protein that has both extracellular and intracellular functions. Despite a clear causal role in cancer development, the contributions of intracellular IGFBP2 to tumor development and progression are poorly understood. Here we present evidence that both exogenous IGFBP2 treatment and cellular IGFBP2 overexpression lead to aberrant activation of EGFR, which subsequently activates STAT3 signaling. Furthermore, we demonstrate that IGFBP2 augments the nuclear accumulation of EGFR to potentiate STAT3 transactivation activities, via …


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