Life Sciences Commons^™

Pvt1 Exon 9: A Potential Biomarker Of Aggressive Prostate Cancer?, Adeodat Ilboudo, Jyoti Chouhan, Brian K. Mcneil, Joseph R. Osborne, Olorunseun O. Ogunwobi

Publications and Research

Prostate cancer (PCa) is the most commonly diagnosed cancer as well as the greatest source of cancer-related mortality in males of African ancestry (MoAA). Interestingly, this has been shown to be associated with single nucleotide polymorphisms around regions 2 and 3 of the 8q24 human chromosomal region. The non-protein coding gene locus Plasmacytoma Variant Translocation 1 (PVT1) is located at 8q24 and is overexpressed in PCa and, therefore, is also a candidate biomarker to explain the well-known disparity in this group. PVT1 has at least 12 exons that make separate transcripts which may have different functions, all of which are …

Thinking Beyond The Fried Egg Model: How Accurately Do Students Perceive Cells In A Living Context?, Milissa Knox

Electronic Theses and Dissertations

This exploratory study investigated three aspects of introductory undergraduate biology students’ understanding about cells. The study, which took place at the University of Maine with voluntary students in Basic Biology (“BIO100”) in the summer and fall of 2009, examined (1) students’ pre-course perceptions of cells as they exist in a living context and (2) gains in students’ perception and knowledge about cells after completing the one-semester course (BIO100). Results are based on lecture exam scores, pre-post surveys developed as a part of this thesis, and interviews with two groups of biology students. A total of 498 students participated in the …

The Role Of Tumor Suppressor Co-Chaperone Chip/Stub1 In Erbb2-Mediated Oncogenesis, Haitao Luan

Theses & Dissertations

The epidermal growth factor receptor (EGFR) family member ErbB2 (Her2) is overexpressed in 20 -30% of invasive breast cancers and this overexpression correlates with poor prognosis and shorter overall as well as disease-free survival. Aberrant expression of ErbB2 through gene amplification, transcriptional deregulation and/or altered endocytic trafficking results in overexpression of ErbB2 at the plasma membrane and biases ErbB2 from primarily ligand-driven hetero-dimerization under normal expression conditions to increased ligand-independent homo-dimer and hetero-dimer formation and consequent activation. C-terminus of HSC70-Inteeracting protein (CHIP)/STIP1-homologous U-Box containing protein 1 (STUB1) is an HSP90/HSC70 interacting negative co-chaperone known to promote ubiquitination and degradation of …

Acute Methamphetamine Exposure Affects Histone Modifying Enzymes And Cytokine Production In Macrophages, Ariel Burns

Theses & Dissertations

The effects of methamphetamine (Meth) in the periphery are not well studied and a comprehensive investigation on the effects and molecular mechanism will give insight into why Meth users are at an increased risk of infections. For this reason, we use macrophages as a model for the immune system dysregulation seen in Meth abusers and also because macrophages are a long-lived cell that HIV infects and persists in. We aimed to determine the effects of Meth on the cytokine production, histone modifying enzymes and the corresponding histone post-translational modifications, and the molecular mechanism in HIV-infected human macrophages treated with combination …

The Role Of Cxcr2 In Pancreatic Cancer Development And Progression, Abhilasha Purohit

Theses & Dissertations

This dissertation examines the role of CXCR2, a seven transmembrane G- protein coupled receptor, in mediating autocrine as well as paracrine mechanisms during pancreatic cancer progression. Data presented in the initial section demonstrates the aberrant expression of the CXCR2 biological axis in human pancreatic cancer tissue specimens. A study performed within the first section of this dissertation investigates the contribution of CXCR2 signaling in pancreatic cancer initiation. These studies have identified a novel role of CXCR2 in mediating KRAS^(G12D) -induced autocrine growth transformation of pancreatic cancer cells. The upregulation of the CXCR2 biological axis was found to be directly …

Atypical Protein Kinase C Dependent Polarized Cell Division Is Required For Myocardial Trabeculation, Derek L. Passer

Theses & Dissertations

A hallmark of cardiac development is the formation of myocardial trabeculations exclusively from the luminal surface of the primitive heart tube. Although a number of genetic defects in the endocardium (Grego-Bessa et al., 2007; Liu et al., 2010) and cardiac jelly (Camenisch et al., 2000) disrupt myocardial trabeculation, the role of cell polarity machinery in driving this process remains unclear. Herein, we demonstrate that atypical protein kinase C iota (Prkci) and its interacting partners of Par polarity complex are localized to the luminal side of luminal myocardial cells. Remarkably, a subset of these cells undergoes polarized cell division with the …

A Role For Ehd Family Endocytic Regulators In Endothelial Biology, Alexandra E. J. Moffitt

Theses & Dissertations

Endocytic trafficking is an essential process in eukaryotic cells, specifically for the transport of nutrients, membrane components, and receptors. Cargo destined for endocytic traffic is internalized at the cell surface via clathrin-dependent and clathrin-independent pathways, and brought to the early or sorting endosomes. From there, cargo is further trafficked to lysosomes for degradation, trafficked to other compartments in the cell, or recycled back to the cell surface (either directly or via the endocytic recycling compartment).

Mammalian C-terminal Eps15 homology domain-containing proteins, or EHD proteins (EHD1 to 4), are a family of highly conserved ATPases that function as key regulators of …

The Role Of Bone Sialoprotein In Periodontal Tissue Development And Bone Repair, Yohannes Soenjaya

Electronic Thesis and Dissertation Repository

Bone development and repair involve complex processes that include interaction between cells and their surrounding matrix. In the body, bone sialoprotein (BSP) expression is up-regulated at the onset of mineralization. BSP is a multifunctional acidic phosphoprotein with collagen-binding, hydroxyapatite nucleating, and integrin recognition (RGD sequence, which is important for cell-attachment and signaling) regions. Mice lacking BSP expression (Bsp^-/-), exhibit a bone phenotype with reductions in bone mineral density, bone length, osteoclast activation, and impaired bone healing. This thesis examined the role of BSP in tooth development and also its potential use as a therapeutic reagent for bone …

Parn Deadenylase Is Involved In Mirna-Dependent Degradation Of Tp53 Mrna In Mammalian Cells, Xiaokan Zhang, Emral Devany, Michael R. Murphy, Galina Glazman, Mirjana Persaud, Frida E. Kleiman

Publications and Research

mRNA deadenylation is under the control of cis-acting regulatory elements, which include AU-rich elements (AREs) and microRNA (miRNA) targeting sites, within the 3′ untranslated region (3′ UTRs) of eukaryotic mRNAs. Deadenylases promote miRNA-induced mRNA decay through their interaction with miRNA-induced silencing complex (miRISC). However, the role of poly(A) specific ribonuclease (PARN) deadenylase in miRNA-dependent mRNA degradation has not been elucidated. Here, we present evidence that not only ARE- but also miRNA-mediated pathways are involved in PARN-mediated regulation of the steady state levels of TP53 mRNA, which encodes the tumor suppressor p53. Supporting this, Argonaute-2 (Ago-2), the core component of miRISC, …

Investigation Of Cell-Penetrating Peptide Transformation In Two Regenerable Tissue Culture Systems, Atiyyah S. Ferouz

Electronic Thesis and Dissertation Repository

The genetic engineering of plants allows for the modification of plant genomes, subsequently improving plant traits. There are, however, plants recalcitrant to established transformation methods, requiring the implementation of novel techniques. This study investigates the viability of cell-penetrating peptide (CPP) transformation using Tat₂, a CPP with demonstrated transformation efficiency in plant and animal systems, in two regenerable tissue culture systems, soybean somatic embryos and Arabidopsis protoplasts. Assessments of complex formation, Tat₂ cellular translocation, complex uptake, and CPP-mediated transformation were carried out. The results show the formation of a Tat₂-plasmid complex and the uptake of Tat …

Hd2d Is A Regulator Of Abscisic Acid Responses In Arabidopsis, Joshua A. Farhi

Electronic Thesis and Dissertation Repository

Histone deacetylases have important roles in development and stress response in plants. To further investigate their function, the HD2D gene, of the plant specific HD2 family, was studied. An hd2d-1 mutant and two HD2D overexpression lines were used in this study. Germination was delayed in hd2d-1 and HD2D overexpression seeds only in the presence of ABA. HD2D was found to positively regulate the expression of members of the ABA-response pathway (ABI1, ABI5, and RD29A) leading to increased resistance to drought and salinity treatments. Furthermore, HD2D expression delayed flowering by positively regulating FLC expression. Using bimolecular fluorescence complementation, the HD2D protein …

Substrate Rigidity Regulates The Formation And Maintenance Of Tissues, Wei-Hui Guo, Margo Frey, Nancy Burnham, Yu-Li Wang

Nancy A. Burnham

The ability of cells to form tissues represents one of the most fundamental issues in biology. However, it is unclear what triggers cells to adhere to one another in tissues and to migrate once a piece of tissue is planted on culture surfaces. Using substrates of identical chemical composition but different flexibility, we show that this process is controlled by substrate rigidity: on stiff substrates, cells migrate away from one another and spread on surfaces, whereas on soft substrates they merge to form tissue-like structures. Similar behavior was observed not only with fibroblastic and epithelial cell lines but also explants …

Fgf2-Induced Effects On Transcriptome Associated With Regeneration Competence In Adult Human Fibroblasts, Olga Kashpur, David Lapointe, Sakthikumar Ambady, Elizabeth Ryder, Tanja Dominko

Sakthikumar Ambady

BACKGROUND: Adult human fibroblasts grown in low oxygen and with FGF2 supplementation have the capacity to tip the healing outcome of skeletal muscle injury - by favoring regeneration response in vivo over scar formation. Here, we compare the transcriptomes of control adult human dermal fibroblasts and induced regeneration-competent (iRC) fibroblasts to identify transcriptional changes that may be related to their regeneration competence. RESULTS: We identified a unique gene-expression profile that characterizes FGF2-induced iRC fibroblast phenotype. Significantly differentially expressed genes due to FGF2 treatment were identified and analyzed to determine overrepresented Gene Ontology terms. Genes belonging to extracellular matrix components, adhesion …

Assessing Ethical Awareness In A Molecular And Cellular Biology Major, Heather G. Kuruvilla

Science and Mathematics Faculty Presentations

No abstract provided.

Netrin-1 Signaling In Tetrahymena Thermophila: The Tyrosine Kinase Controversy Continues, Matthew S. Merical, Heather G. Kuruvilla

Science and Mathematics Faculty Presentations

Netrin-1 is a pleiotropic signaling molecule first discovered for its role in neuronal development, where it is largely responsible for axonal guidance. When signaling through the DCC receptor, netrin-1 serves as a chemoattractant; however, signaling through the UNC5 receptor results in chemorepulsive activity (Ko et al., 2012). In the free-living ciliate, Tetrahymena thermophila, netrin-1 and netrin-1 peptide act as chemorepellents at micromolar to nanomolar concentrations, causing cells to exhibit avoidance behavior. While many pharmacological inhibitors that we tested had no effect on avoidance behavior, the tyrosine kinase inhibitor, genistein (IC50 ~ 50 μg/ml), inhibited avoidance behavior in this organism. However, …

Is The Zebrafish Zombie Mutant Caused By A Mutation In Cdc20?, Peyton Johnston

Honors Theses

The zombie mutant was identified as an early arrest mutant, stopping in development around the 10-somite stage (14 hours of development). Further inspection revealed that this mutant was a cell cycle mutant and cells in the mutant arrest during metaphase as early as the 5-somite stage (11.6 hours of development). A similar phenotype is seen in the Drosophila melanogaster cell cycle gene fizzy, known to be to be a homolog of the Saccharomyces cerevisiae gene, cell division cycle 20 (cdc20). CDC20 is an activator protein of the anaphase promoting complex/cyclosome (APC/C), an ubiquitin E3 ligase that is …

Genetic Modification Of Human Mesenchymal Stem Cells Helps To Reduce Adiposity And Improve Glucose Tolerance In An Obese Diabetic Mouse Model., Sabyasachi Sen, Cleyton C Domingues, Carol Rouphael, Cyril Chou, Chul Kim, Nagendra Yadava

Medicine Faculty Publications

INTRODUCTION: Human mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into fat, muscle, bone and cartilage cells. Exposure of subcutaneous abdominal adipose tissue derived AD-MSCs to high glucose (HG) leads to superoxide accumulation and up-regulation of inflammatory molecules. Our aim was to inquire how HG exposure affects MSCs differentiation and whether the mechanism is reversible.

METHODS: We exposed human adipose tissue derived MSCs to HG (25 mM) and compared it to normal glucose (NG, 5.5 mM) exposed cells at 7, 10 and 14 days. We examined mitochondrial superoxide accumulation (Mitosox-Red), cellular oxygen consumption rate (OCR, Seahorse) and gene …

Erbeta Regulation Of Nf-Kb Activation In Prostate Cancer Is Mediated By Hif-1, Paul Mak, Jiarong Li, Sanjoy Samanta, Arthur M. Mercurio

Arthur M. Mercurio

We examined the regulation of NF-kappaB in prostate cancer by estrogen receptor beta (ERbeta) based on the inverse correlation between p65 and ERbeta expression that exists in prostate carcinomas and reports that ERbeta can inhibit NF-kappaB activation, although the mechanism is not known. We demonstrate that ERbeta functions as a gate-keeper for NF-kappaB p65 signaling by repressing its expression and nuclear translocation. ERbeta regulation of NF-kappaB signaling is mediated by HIF-1. Loss of ERbeta or hypoxia stabilizes HIF-1alpha, which we found to be a direct driver of IKKbeta transcription through a hypoxia response element present in the promoter of the …

Brown And Beige Adipocytes: Effects Of Inflammation And Nutritional Intervention, Jiyoung Bae

Doctoral Dissertations

Recent findings of brown adipocytes and brown-like or beige adipocytes, capable of dissipating energy as heat, in adult humans have promised new hope for obesity treatment and prevention. Understanding of the regulation of brown and beige adipocytes will provide novel strategies to reach the goal. Pattern recognition receptors (PRR) are responsible for inflammation in adipose tissue, which leads to adipose dysfunction and obesity associated chronic diseases. It has been shown that PRR activation induces inflammation, leading to insulin resistance in white adipocytes and white adipose tissue (WAT). However, the roles of PRR activation in brown adipocytes and brown adipose tissue …

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

Dissertations & 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 …

A Synthetic Porcine Reproductive And Respiratory Syndrome Virus Strain Confers Unprecedented Levels Of Heterologous Protection, Hiep Vu, Fangrui Ma, William W. Laegreid, Asit K. Pattnaik, David Steffen, Alan R. Doster, Fernando Osorio

School of Veterinary and Biomedical Sciences: Faculty Publications

Current vaccines do not provide sufficient levels of protection against divergent porcine reproductive and respiratory syndrome virus (PRRSV) strains circulating in the field, mainly due to the substantial variation of the viral genome. We describe here a novel approach to generate a PRRSV vaccine candidate that could confer unprecedented levels of heterologous protection against divergent PRRSV isolates. By using a set of 59 nonredundant, full-genome sequences of type 2 PRRSVs, a consensus genome (designated PRRSV-CON) was generated by aligning these 59 PRRSV full-genome sequences, followed by selecting the most common nucleotide found at each position of the alignment. Next, the …

Declining Incidence Of Stroke And Dementia: Coincidence Or Prevention Opportunity?, Luciano A. Sposato, Moira K. Kapral, Jiming Fang, Sudeep S. Gill, Daniel G. Hackam, Lauren E. Cipriano, Vladimir Hachinski

Anatomy and Cell Biology Publications

No abstract provided.

The Role Of G-Protein Signaling In Pathogenesis In Cercospora Zeae-Maydis, Brant Smith

Graduate Theses and Dissertations

Gray leaf spot, caused by Cercospora zeae-maydis, is one of the most destructive foliar diseases of maize worldwide. C. zeae-maydis orients hyphal growth towards stomata (stomatal tropism) and forms infectious structures (appressoria) that are necessary for successful infection. Although some genes involved in pathogenesis in C. zeae-maydis have been identified, the molecular mechanisms are not well understood. In fungi, heterotrimeric G-proteins consist of three subunits (α, β, and γ) and mediate responses to environmental stimuli. They regulate diverse functions, including nutrient detection, virulence, fungal development, conidiation, secondary metabolism, and pathogenesis in many plant pathogenic fungi. This research explored the role …

Role Of Stat3 In Human Nk Cell Functions, Prasad V. Phatarpekar

Dissertations & Theses (Open Access)

Natural Killer (NK) cells are cytotoxic lymphocytes, which play a critical role in the immune response against malignant cells and microbial infections. NK cells are equipped with activating receptors, which upon detecting ligands expressed on stressed cells induce cytolytic activity of NK cells. Stimulation of NK cell proliferation and priming of NK cytolytic capability are accomplished by cytokines, which mediate their signals mainly through JAK-STAT signaling pathway. Previously, we found that K562 cells genetically modified to express membrane bound IL-21 (mbIL-21), which predominantly activates STAT3, induce robust expansion and activation of human NK cells. Further investigations revealed role of STAT3 …

Identifying Protein Kinase Tbk1 As A Novel Inhibitor Of Intestinal Tumorigenesis, Amber L. Mathews

Dissertations & Theses (Open Access)

Colorectal cancer (CRC) is the third most common cancer diagnosed in women and men， causing almost 600,000 annual deaths worldwide. There is a clear need to understand how CRC forms and progresses in order to improve the strategies of CRC prevention and therapy. A major factor that drives the development of CRC is genetic mutations that lead to activation of oncogenes and inactivation of tumor suppressor genes in intestinal epithelial cells (IECs). In addition, the initiation and progression of CRC involve environmental and immunological factors. In particular, chronic inflammatory conditions are known as an important risk factor for CRC. Intestinal …

The Tumor Suppressor Notch Inhibits Head And Neck Squamous Cell Carcinoma (Hnscc) Tumor Growth And Progression By Modulating Proto-Oncogenes Axl And Ctnnal1 (Α-Catulin), Shhyam Moorthy, Shhyam Moorthy

Dissertations & Theses (Open Access)

Background: Head and Neck Squamous Cell Carcinoma (HNSCC) is the sixth most common malignancy worldwide, with roughly 300,000 cancer related deaths occurring globally each year. The survival of patients with HNSCC has not changed significantly over the past decade, leading investigators to search for promising molecular targets. To identify new treatment targets and biomarkers that could better guide therapy, we previously characterized the genomic alterations from primary HNSCC patient samples. We were among the first to discover that NOTCH1 is one of the most frequently mutated genes in this cancer type. The spectrum of inactivating NOTCH1 mutations in HNSCC suggested …

Effects Of Bone Morphogenetic Protein-2 And Parathyroid Hormone-Related Peptide On Collagen Xi During Skeletal Development, Neda Shefa

Boise State University Theses and Dissertations

Long bones develop via endochondral ossification, a process in which cartilage precedes bone. During endochondral ossification prechondrogenic cells undergo proliferation and apoptose as cells of the periosteum differentiate into bone. The process of endochondral ossification is regulated by a group of endocrine as well as paracrine molecules that includes bone morphogenetic protein-2 (BMP-2) and parathyroid hormone-related peptide (PTHrP). Collagens are extracellular matrix molecules that are present in a spatiotemporal manner during endochondral ossification. Collagen XI alpha 1 (Col11a1) is a minor fibrillar collagen that is alternatively spliced during development and can result in up to eight different spliceforms. During endochondral …

Eicosapentaenoic Acid (Epa) From Porphyridium Cruentum: Increasing Growth And Productivity Of The Microalgae For Pharmaceutical Products, Maryam Asgharpour

Graduate Theses and Dissertations

One of the major nutritional requirements in our diet is an adequate intake of omega-3 specially eicosapentaenoic acid (EPA). In the present study, the effects of two temperatures (16°C & 20˚C) and light intensities (140 & 180µE/M2.S) and four nitrate levels (0.075, 0.3, 0.5 and 0.7g/L) on the cell growth and lipid productivity of Porphyridium cruentum, one of the most promising oil-rich species of microalgae, were investigated. A growth comparison was carried out using pure CO2 and 5% CO2/air. Additionally, the ratio of the fatty acids with omega-3 and omega-6 groups at various growth conditions were compared, since an appropriate …

Response Of Bacterial Cells To Fluctuating Environment, Sudip Nepal

Graduate Theses and Dissertations

We have studied morphological and genomic variations occurring in a mesophilic bacterium Escherichia coli (E. coli) in a wide range of continuous and fluctuating hydrostatic pressures. For all the studies here the temperature is maintained at 37◦C, the optimal growth tem- perature of E. coli at atmospheric pressure. Cell division is inhibited at high hydrostatic pressures resulting in an increase of cell length. The increase of cell-length depends on the extent and duration of the stress applied on bacterial cells. We have studied the effect of high pressure stress in three different conditions – (i) Wild-type cells (almost no genetic …

The Neurobiology Of Circadian Rhythms, Patricia J. Sollars, Gary E. Pickard

School of Veterinary and Biomedical Sciences: Faculty Publications

Daily rhythms in nature, such as the opening and closing of flowers or our patterns of sleep and wakefulness and their association with the perpetual alteration of night and day, were recognized in antiquity although their origins were not questioned until the eighteenth century. The French Astronomer Jean-Jacques d’Ortous de Mairan conducted an investigation into whether the leaves of the Mimosa plant opened in response to light.¹ While de Mairan’s experiments were the first to question the origin of such daily rhythms, Augustin Pyramus de Candolle is credited with the first suggestion that they arose through an internal timekeeping …