Phosphoinositides: Minor Lipids Make A Major Impact On Photoreceptor Cell Functions, 2014 University of Oklahoma
Phosphoinositides: Minor Lipids Make A Major Impact On Photoreceptor Cell Functions, Raju V. S. Rajala, Ammaji Rajala, Andrew J. Morris, Robert E. Anderson
Internal Medicine Faculty Publications
Activation of the phosphoinositide (PI) cycle generates the second messengers that control various aspects of cellular signaling. We have previously shown that two PI cycle enzymes, type II phosphatidylinositol 5-phosphate 4-kinase (PIPK IIα) and phosphoinositide 3-kinase (PI3K), are activated through light stimulation. In our earlier studies, we measured enzyme activities, instead of directly measuring the products, due to lack of sensitive analytical techniques. Cells have very low levels of PIs, compared to other lipids, so special techniques and sensitive analytical instruments are necessary for their identification and quantification. There are also other considerations, such as different responses in different cell …
Manipulating The Tumor Microenvironment For Therapeutic Benefit, 2014 University of South Florida
Manipulating The Tumor Microenvironment For Therapeutic Benefit, Kate M. Bailey
USF Tampa Graduate Theses and Dissertations
The physical tumor microenvironment contributes significantly to carcinogenesis, cancer progression and metastatic dissemination. Two main components of the tumor microenvironment, hypoxia and acidosis, are present in nearly every solid tumor and act as powerful selection forces against the tumor. Hypoxia and acidosis promote tumor heterogeneity and contribute to chemotherapy and radiotherapy resistance. This dissertation interrogates methods to target the tumor microenvironment including two novel studies describing mechanisms of buffer therapy resistance and targeting tumor hypoxia with vasodilators to enhance the efficacy of a hypoxia activated prodrug, TH-302.
In the first study, mechanisms of buffer therapy resistance were identified and detailed. …
Fty720 (Fingolimod) Provides Insight Into The Molecular Mechanisms Of Multiple Sclerosis, 2014 University of Tennessee, Knoxville
Fty720 (Fingolimod) Provides Insight Into The Molecular Mechanisms Of Multiple Sclerosis, Madelyn Elizabeth Crawford
Pursuit - The Journal of Undergraduate Research at The University of Tennessee
Multiple sclerosis (MS) is a neurodegenerative disorder caused by a prolonged immune- mediated inflammatory response that targets myelin. Nearly all of the drugs approved for the treatment of MS are general immunosuppressants or only function in symptom management. The oral medication fingolimod, however, is reported to have direct therapeutic effects on cells of the central nervous system in addition to immunomodulatory functions. Fingolimod is known to interact with sphingosine-1-phosphate (S1P) receptors, and the most widely- accepted theory for its mechanism of action is functional antagonism of the receptor. This review examines significant neuromodulatory effects achieved by functional antagonism of the …
Islet Regenerative Properties Of Ex Vivo Expanded Hematopoietic Progenitor Cells, 2014 The University of Western Ontario
Islet Regenerative Properties Of Ex Vivo Expanded Hematopoietic Progenitor Cells, Ayesh K. Seneviratne
Electronic Thesis and Dissertation Repository
Human umbilical cord blood (UCB) progenitor cells with high aldehyde dehydrogenase activity (ALDHhi), can stimulate endogenous islet regeneration after transplantation into mice with steptozotocin (STZ)-induced diabetes. However, UCB ALDHhi cell are extremely rare, and expansion will be required to develop cell-mediated strategies to treat patients with diabetes. To increase the number of progenitor cells available for clinical application, we expanded ALDHhi UCB cells under clinically applicable, serum-free hematopoietic-restricted conditions. 6 day expansion resulted in a 15-fold increase in total cell number, and a 3-fold increase in the number of HPC retaining high ALDH (ALDHhi HPC) …
The Role Of The N-Terminus On The Enzymatic Activity Of Dutpase From Dictyostelium Discoideum, 2014 University of Nebraska-Lincoln
The Role Of The N-Terminus On The Enzymatic Activity Of Dutpase From Dictyostelium Discoideum, Kyle C. Varon
School of Biological Sciences: Dissertations, Theses, and Student Research
The enzyme deoxyuridine triphosphatase (dUTPase) (EC 3.6.1.23) converts dUTP to dUMP, thus shifting the dUTP to dUMP ratio in the cell. The molecule dUTP is subject to mis-incorporation into DNA due to lack of distinguishing by DNA polymerase. Uracil incorporation can be repaired with base excision repair mechanisms but may create overwhelming DNA strand breaks proving to be detrimental to the cell. Most dUTPases of eukaryotes are homotrimeric and contain five highly conserved motifs responsible for catalysis and substrate binding. Many dUTPases of eukaryotes possess a leading and core region in their sequence. The core region is composed of the …
Truncation Of Type Iv Pilin Induces Mucoidy In Pseudomonas Aeruginosa Strain Pao579, 2014 Marshall University
Truncation Of Type Iv Pilin Induces Mucoidy In Pseudomonas Aeruginosa Strain Pao579, T. Ryan Withers, F. Heath Damron, Yeshi Yin, Hongwei D. Yu
Hongwei Yu
Pseudomonas aeruginosa is a Gram negative, opportunistic pathogen that uses the overproduction of alginate, a surface polysaccharide, to form biofilms in vivo. Overproduction of alginate, also known as mucoidy, affords the bacterium protection from the host's defenses and facilitates the establishment of chronic lung infections in individuals with cystic fibrosis. Expression of the alginate biosynthetic operon is primarily controlled by the alternative sigma factor AlgU (AlgT/σ22). In a nonmucoid strain, AlgU is sequestered by the transmembrane antisigma factor MucA to the cytoplasmic membrane. AlgU can be released from MucA via regulated intramembrane proteolysis by proteases AlgW and MucP causing the …
Impedimetric Detection Of Mutant P53 Biomarker-Driven Metastatic Breast Cancers Under Hyposmotic Pressure, 2014 CUNY Hunter College
Impedimetric Detection Of Mutant P53 Biomarker-Driven Metastatic Breast Cancers Under Hyposmotic Pressure, Menglu Shi, Nataly Shtraizent, Alla Polotskaia, Jill Bargonetti, Hiroshi Matsui
Publications and Research
In cancer cells, the oncogenic mutant p53 (mtp53) protein is present at high levels and gain-of-function (GOF) activities with more expression of mtp53 proteins contribute to tumor growth and metastasis. Robust analytical approaches that probe the degree of metastasis of cancer cells in connection with the mtp53 activity will be extremely useful not only for establishing a better cancer prognosis but also understanding the fundamental mechanism of mtp53 oncogenic action. Here we assessed the influence of mtp53 in breast cancers to the mechanical property of breast cancer cells. Recently, ovarian and kidney cancer cell lines have been shown to have …
Investigating Microenvironmental Regulation Of Human Chordoma Cell Behaviour, 2014 The University of Western Ontario
Investigating Microenvironmental Regulation Of Human Chordoma Cell Behaviour, Priya Patel
Electronic Thesis and Dissertation Repository
The tumor microenvironment is complex and often includes matricellular proteins and regions of hypoxia, which can promote stem and progenitor properties that regulate cancer cell biology. We hypothesized that hypoxia and CCN2 would promote notochord progenitor-like characteristics in human chordoma (U-CH1) cells, and assessed cell phenotype using Real-time qPCR and in vitro functional assays. We found the expression of CCN family members CCN1, CCN2, CCN3 and CCN5 in U-CH1 cells. We demonstrate that hypoxia and CCN2 promoted progenitor-like characteristics specific to the notochordal tissue of origin. Specifically, hypoxia had the greatest ability to promote progenitor characteristics (increase in notochord markers …
Kiss1r Signaling Promotes Breast Cancer Metastasis, 2014 The University of Western Ontario
Kiss1r Signaling Promotes Breast Cancer Metastasis, Cameron G-F Goertzen
Electronic Thesis and Dissertation Repository
Kisspeptins, peptide products of KISS1, are endogenous ligands for KISS1R, a G protein-coupled receptor. In numerous cancers, KISS1 acts as a metastasis suppressor. However, studies have revealed that patients with elevated KISS1 and KISS1R breast tumor expression have increased tumor grade, increased lymph node metastases and poor survival. We hypothesize that depletion of KISS1R inhibits breast cancer cell metastasis. In order to assess the role of KISS1R in breast cancer metastasis, we used a pre-clinical orthotopic xenograft mouse model using MDA-MB-231 breast cancer cells for breast tumor establishment. We discovered that depletion of KISS1R decreased primary tumor growth and …
Vitamin A Deficiency Causes Ovulation Abnormalities In Mice, 2014 DePaul University
Vitamin A Deficiency Causes Ovulation Abnormalities In Mice, Rebecca Ursin
DePaul Discoveries
Retinoic acid (RA) is an active metabolite of vitamin A (VA) and is involved in tissue organization, patterning, and growth. RA has been shown to regulate male reproduction, however information on its role in ovary development is limited. To investigate the functions of RA in the ovary, we examined its role in ovary development and ovulation using an in vivo dietary VA-deprivation animal model. Our preliminary results have shown that VA deficiency causes a variety of ovarian pathologies, including reduced numbers of total follicles and corpus lutea, formation of hemorrhagic and atretic follicles, and formation of bursa and follicular cysts. …
Characterization Of The Anti-Apoptotic Function Of The Lysine Demethylase Plant Homeodomain Finger Protein 8 (Phf8), 2014 The University of Western Ontario
Characterization Of The Anti-Apoptotic Function Of The Lysine Demethylase Plant Homeodomain Finger Protein 8 (Phf8), Kimberly Muranko
Electronic Thesis and Dissertation Repository
Apoptosis is an essential process in development and tissue maintenance. The tumor suppressor protein p53 initiates apoptosis through transactivation of pro-apoptotic genes when cellular stress is detected. This study identifies a regulatory role for the lysine demethylase, PHF8, in the p53-mediated apoptosis pathway. We initially suspected PHF8 of demethylating the adaptor protein Numb, however found this to be untrue. PHF8 has been found to have oncogenic properties including an anti-apoptotic effect, however how PHF8 negatively affects apoptosis has not been previously investigated. We found PHF8 inhibits translation of the pro-apoptotic genes TP53, BAX and CASP3. Chromatin immunoprecipitation revealed …
Determining The Potential Activity Of Wnt Signaling During Zebrafish Oocyte Maturation, 2014 University of Puget Sound
Determining The Potential Activity Of Wnt Signaling During Zebrafish Oocyte Maturation, Nathan Pincus
Honors Program Theses
During maturation, the oocyte (immature egg) progresses from prophase I to metaphase II of meiosis and a multitude of cellular changes occur. In zebrafish, oocyte maturation is triggered by 17α,20β-dihydroprogesterone (DHP), which binds to a membrane-bound receptor, however the extent of communication between the oocyte and its environment is not fully understood. Wnt signaling pathways are known to regulate gene expression, cell behavior, cell adhesion, and cell polarity, as well as play an essential role in embryonic development. In this study, I investigated the potential activity of Wnt signaling pathways during zebrafish oocyte maturation by examining the gene expression of …
The Role Of Mir-526b In Cox-2 Mediated Human Breast Cancer Progression And Induction Of Stem-Like Phenotype Via Ep4 Receptor Signaling, 2014 The University of Western Ontario
The Role Of Mir-526b In Cox-2 Mediated Human Breast Cancer Progression And Induction Of Stem-Like Phenotype Via Ep4 Receptor Signaling, Erin O. Landman
Electronic Thesis and Dissertation Repository
Our laboratory previously established that aberrant expression of cyclo-oxygenase (COX)-2 promotes breast cancer progression and metastasis via multiple mechanisms, including stem-like cell (SLC) induction, owing to activation of the prostaglandin E2 receptor EP4. COX-2 expression was linked to up-regulation of miRNA-526b. We hypothesized that miR-526b is regulated by EP4 activity, and that miR-526b supports breast cancer progression and induction of SLCs. Using stably miR-526b transfected MCF-7 and SKBR-3 cells in functional assays, including tumorsphere formation in vitro and lung colony formation in vivo, we observed enhanced migration, invasion, proliferation, tumorsphere formation, and in vivo tumorigenecity compared to controls. EP4 …
Cholinergic Signaling Exerts Protective Effects In Models Of Sympathetic Hyperactivity-Induced Cardiac Dysfunction, 2014 Universidade Federal de Minas Gerais
Cholinergic Signaling Exerts Protective Effects In Models Of Sympathetic Hyperactivity-Induced Cardiac Dysfunction, Mariana Gavioli, Aline Lara, Pedro W. M. Almeida, Augusto Martins Lima, Denis D. Damasceno, Cibele Rocha-Resende, Marina Ladeira, Rodrigo R. Resende, Patricia M. Martinelli, Marcos Barrouin Melo, Patricia C. Brum, Marco Antonio Peliky Fontes, Robson A. Souza Santos, Marco A. M. Prado, Silvia Guatimosim
Anatomy and Cell Biology Publications
Cholinergic control of the heart is exerted by two distinct branches; the autonomic component represented by the parasympathetic nervous system, and the recently described non-neuronal cardiomyocyte cholinergic machinery. Previous evidence has shown that reduced cholinergic function leads to deleterious effects on the myocardium. Yet, whether conditions of increased cholinergic signaling can offset the pathological remodeling induced by sympathetic hyperactivity, and its consequences for these two cholinergic axes are unknown. Here, we investigated two models of sympathetic hyperactivity: i) the chronic beta-adrenergic receptor stimulation evoked by isoproterenol (ISO), and ii) the alpha(2A)/alpha(2C)-drenergic receptor knockout (KO) mice that lack pre-synaptic adrenergic receptors. …
Tattletales And T-Bow Update 20140602mon, 2014 M.D. Anderson Cancer Center
Tattletales And T-Bow Update 20140602mon, George Mcnamara
George McNamara
Tattletales and T-Bow Update 20140602Mon
http://works.bepress.com/gmcnamara/42
Please see also http://works.bepress.com/gmcnamara/26
Tattletales: multiplex fluorescent protein biosensors by spatial localization with TALE-FPs, Cas9-FPs, ZF-FPs, LacI-FPs, TetR-FPs, etc.
T-Bow: Rainbow T-cells and Tumor cells (and ES cells, iPS cells, other cells and organisms). You can think of this as "Brainbow meets TALENs/Cas9/ZFNs/other DNA sequence specific binding proteins".
If not familiar with Brainbow, see
http://en.wikipedia.org/wiki/Brainbow
If not familiar with TALENs, Cas9, etc, see
http://www.addgene.org/genome_engineering/
Big idea: localizing fluorescent proteins - and/or Nano-Lanterns (Take Nagai) - to tandem repeat arrays - is a great way to improve signal to noise ratio compared to the usual …
Expression Of Osteoarthritis Biomarkers In Temporomandibular Joints Of Mice With And Without Receptor For Advanced Glycation End Products (Rage), 2014 Brigham Young University - Provo
Expression Of Osteoarthritis Biomarkers In Temporomandibular Joints Of Mice With And Without Receptor For Advanced Glycation End Products (Rage), Elizabeth Murayama Chavez Matias
Theses and Dissertations
This thesis will be organized into three chapters discussing the mechanism underlying the onset and progression of osteoarthritis (OA) in the temporomandibular joint (TMJ). Understanding the mechanism of OA development in the TMJ helps in understanding how OA progresses and how to treat this disease. The goal of this investigation is to examine the process of cartilage degeneration and OA biomarker expression in the TMJ to understand their role in TMJ OA onset and development.Chapter one covers mechanisms that are altered in TMJ OA during disease progression. Using animal models with different stressors such as mechanical disturbances, direct injury, and …
Identification Of Novel Small Rnas And Characterization Of The 6s Rna Of Coxiella Burnetii, 2014 University of Montana - Missoula
Identification Of Novel Small Rnas And Characterization Of The 6s Rna Of Coxiella Burnetii, Indu Warrier, Linda D. Hicks, James M. Battisti, Rahul Raghavan, Michael F. Minnick
Biology Faculty Publications and Presentations
Coxiella burnetii, an obligate intracellular bacterial pathogen that causes Q fever, undergoes a biphasic developmental cycle that alternates between a metabolically-active large cell variant (LCV) and a dormant small cell variant (SCV). As such, the bacterium undoubtedly employs complex modes of regulating its lifecycle, metabolism and pathogenesis. Small RNAs (sRNAs) have been shown to play important regulatory roles in controlling metabolism and virulence in several pathogenic bacteria. We hypothesize that sRNAs are involved in regulating growth and development of C. burnetii and its infection of host cells. To address the hypothesis and identify potential sRNAs, we subjected total RNA isolated …
Rapid Adaptation Of Dopamine D2 Receptor Responses In The Brain And Blood Following Acute Ethanol, 2014 Brigham Young University - Provo
Rapid Adaptation Of Dopamine D2 Receptor Responses In The Brain And Blood Following Acute Ethanol, Ryan J. Folsom
Theses and Dissertations
Dopamine (DA) D2 receptor expression parallels DA levels in the brain and these autoreceptors have been shown to be modulated by long-term ethanol exposure. We have previously demonstrated that ventral tegmental area (VTA) GABA neurons also express D2 autoreceptors (D2R), and that DA and D2R agonists markedly enhance the excitability of VTA GABA neurons, opposite to their well-known auto-receptor inhibition of DA neurons. Most importantly, D2R antagonists block ethanol inhibition of VTA GABA neurons and D2R expression in VTA GABA neurons down-regulates with chronic ethanol, as others have shown for whole VTA D2R expression. The aim of this study was …
Examination Of Anabolic Signaling And Muscle Growth With Caffeine Treatment In Overloaded Hindlimb Muscle And Electrically Stimulated Muscle Lacking Liver Kinase B1, 2014 Brigham Young University - Provo
Examination Of Anabolic Signaling And Muscle Growth With Caffeine Treatment In Overloaded Hindlimb Muscle And Electrically Stimulated Muscle Lacking Liver Kinase B1, Timothy Michael Moore
Theses and Dissertations
Skeletal muscle has the ability to increase in size (hypertrophy) after resistance is placed upon it. This hypertrophy is marked by significant upregulation of the mammalian target of rapamycin (mTOR) and its downstream targets. The upstream kinases, protein kinase B (also known as Akt) and AMP-activated protein kinase (AMPK), are two of the many regulators of the mTOR pathway. Recent studies suggest that the widely consumed neuroactive compound caffeine could potentially inhibit mTOR by acting through Akt and/or AMPK. The purpose of this thesis was to: 1) determine if caffeine can inhibit the mTOR pathway and ultimately attenuate skeletal muscle …
Chlorovirus Skp1 And Core Ankyrin-Repeat Protein Interplay And Mimicry Of Cellular Ubiquitin Ligase Machinery, 2014 University of Nebraska-Lincoln
Chlorovirus Skp1 And Core Ankyrin-Repeat Protein Interplay And Mimicry Of Cellular Ubiquitin Ligase Machinery, Eric Andrew Noel
School of Biological Sciences: Dissertations, Theses, and Student Research
The ubiquitin-proteasome system is a common target of several unrelated viruses that have evolved convergent strategies to redirect host ubiquitin machinery to serve their own needs. Members of the genus Chlorovirus, a group of large dsDNA viruses that infect certain freshwater chlorella-like green algae, encode a conserved Skp1 homolog and ankyrin-repeat (ANK) proteins, some of which contain C-terminal domains characteristic of cellular F-boxes or related viral PRANC domains. These observations suggested that this unique combination of chlorovirus proteins either interact with or imitate the key components of the SCF (Skp1-Cul1-F-box) ubiquitin ligases. Using mass spectrometry, we identified two functional …