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Porcine Cytokines, Chemokines And Growth Factors: 2019 Update, Harry D. Dawson, Yongming Sang, Joan K. Lunney 2020 USDA, Agricultural Research Service

Porcine Cytokines, Chemokines And Growth Factors: 2019 Update, Harry D. Dawson, Yongming Sang, Joan K. Lunney

Agricultural and Environmental Sciences Faculty Research

Pigs are a major food source worldwide as well as major biomedical models for human physiology and therapeutics. A thorough understanding of porcine immunity is essential to prevent and treat infectious diseases, and develop effective vaccines and therapeutics. The use of pigs as biomedical models is dependent on the growing molecular and immune toolbox. This paper summarizes current knowledge of swine cytokines, chemokines and growth factors, identifying 289 pig proteins, characterizing knowledge of their gene structures and families. It identifies areas in the current swine genome build that need to be clarified. A broad-based literature and vendor search was conducted …


Effect Of S100b Deletion On Membrane Properties And Localization Of Ncald And Hpca, Natasha Hesketh 2020 Rowan University

Effect Of S100b Deletion On Membrane Properties And Localization Of Ncald And Hpca, Natasha Hesketh

Graduate School of Biomedical Sciences Theses and Dissertations

Calcium signaling is particularly important for neuronal function. Neurons utilize a wide range of calcium-binding proteins. Dysregulation of such proteins is linked to neurodegeneration. Neurocalcin delta (NCALD), hippocalcin (HPCA), and S100B are calcium sensors that are expressed in the hippocampus, a brain region essential to memory and severely damaged in Alzheimer’s disease (AD). Despite the potential importance of these proteins, we do not fully understand the physiological significance of their relationship. Because NCALD and HPCA are known to interact with S100B, we hypothesized that the loss of S100B affects NCALD and HPCA localization, and therefore electrical properties, of hippocampal neurons. …


Epigenetic Targeting Of Mcl-1 Is Synthetically Lethal With Bcl-Xl/Bcl-2 Inhibition In Model Systems Of Glioblastoma, Enyuan Shang, Trang T. T. Nguyen, Chang Shu, Mike-Andrew Westhoff, Georg Karpel-Massler, Markus D. Siegelin 2020 CUNY Bronx Community College

Epigenetic Targeting Of Mcl-1 Is Synthetically Lethal With Bcl-Xl/Bcl-2 Inhibition In Model Systems Of Glioblastoma, Enyuan Shang, Trang T. T. Nguyen, Chang Shu, Mike-Andrew Westhoff, Georg Karpel-Massler, Markus D. Siegelin

Publications and Research

Apoptotic resistance remains a hallmark of glioblastoma (GBM), the most common primary brain tumor in adults, and a better understanding of this process may result in more efficient treatments. By utilizing chromatin immunoprecipitation with next-generation sequencing (CHIP-seq), we discovered that GBMs harbor a super enhancer around the Mcl-1 locus, a gene that has been known to confer cell death resistance in GBM.We utilized THZ1, a known super-enhancer blocker, and BH3-mimetics, including ABT263, WEHI-539, and ABT199. Combined treatment with BH3-mimetics and THZ1 led to synergistic growth reduction in GBM models. Reduction in cellular viability was accompanied by significant cell death induction …


Investigating Chitosan Modified With Triethylammonium Butanamide And Triethylphosphonium Butanamide As Non-Viral Gene Delivery Vectors By Examining Cytotoxicity And Transfection Efficiency, Deborah C. Ehie 2020 Missouri State University

Investigating Chitosan Modified With Triethylammonium Butanamide And Triethylphosphonium Butanamide As Non-Viral Gene Delivery Vectors By Examining Cytotoxicity And Transfection Efficiency, Deborah C. Ehie

Graduate Theses/Dissertations

Gene therapy is a very challenging field, especially with new emerging genetic disorders. Chitosan (CS), due to chitosan’s flexibility, biocompatibility, and biodegradability, has been of interest in the world of gene therapy especially as researchers are gravitating towards non-viral vectors due to the problems caused by viral vectors. Nevertheless, there are still issues regarding solubility, cellular uptake of cargos being transported in vitro or in vivo, increased cytotoxicity levels, as well as many other things that prevent chitosan from being an efficient gene delivery agent. Here I present five derivatives of chitosan, which were all modified with either triethylphosphonium …


Tgfbeta1 And Stat3 As Regulators Of The Ha Synthesis And Signaling Pathway, Brenda Goretty Trevizo 2020 University at Albany, State University of New York

Tgfbeta1 And Stat3 As Regulators Of The Ha Synthesis And Signaling Pathway, Brenda Goretty Trevizo

Legacy Theses & Dissertations (2009 - 2024)

The studies described here explored the role of Transforming Growth Factor Beta-1 (TGFβ1) and Signal Transducer and Activator of Transcription 3 (STAT3) as potential regulators of the Hyaluronic Acid (HA) synthesis and signaling pathway in human mammary cells. Our results support previous findings in which TGFβ1, a well characterized driver of the epithelial-mesenchymal transition (EMT) has been shown to regulate HA synthesis and signaling. Interrogation of The Cancer Genome Atlas (TCGA) indicated HAS2 expression positively correlated with TGFβ1 mRNA expression in breast cancer patients and in breast cancer cell lines. RT-qPCR experiments were used to measure the expression of the …


Tissue-Resident Myeloid-Derived Suppressor Cells Modulate Immune Homeostasis In Healthy Adipose., Katlin Brooke Stivers 2020 University of Louisville

Tissue-Resident Myeloid-Derived Suppressor Cells Modulate Immune Homeostasis In Healthy Adipose., Katlin Brooke Stivers

Electronic Theses and Dissertations

Our goal with this study was to gain insight into the homeostatic immune cell network in healthy adipose tissue. Specifically, we sought to determine if the immature myeloid cells found in healthy and inflamed adipose were, in fact, tissue-resident myeloid-derived suppressor cells (MDSCs). Using various in vitro and in vivo methods, we have uncovered a population of CD11bHi Ly6CHi Ly6G- MDSCs resident in healthy adipose tissue. To the best of our knowledge this is the first time that these cells have been investigated and described in healthy adipose tissue. Systemic MDSC depletion lead to the accumulation of …


Longitudinal Clonal Lineage Dynamics And Functional Characterization Of Pancreatic Cancer Chemo-Resistance And Metastasization, Chieh-Yuan Li 2020 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Longitudinal Clonal Lineage Dynamics And Functional Characterization Of Pancreatic Cancer Chemo-Resistance And Metastasization, Chieh-Yuan Li

Dissertations and Theses (Open Access)

In recent years, technological advancements, such as next-generation sequencing and single-cell interrogation techniques, have enriched our understanding in tumor heterogeneity. By dissecting tumors and characterizing clonal lineages, we are better understanding the intricacies of tumor evolution. Tumors are represented by the presence of and dynamic interactions amongst clonal lineages. Each lineage and each cell contributes to tumor dynamics through intrinsic and extrinsic mechanisms, and the variable responses of clones to perturbations in the environment, especially therapeutics, underlie disease progression and relapse. Thus, there exists a pressing need to understand the molecular mechanisms that determine the functional heterogeneity of tumor sub-clones …


Using Novel Mouse Knockout Models To Study The Roles Of Asm (Acid Sphingomyelinase) In The Regulation Of Multiple Stem Cell Compartments In Vivo, Amro Abdalla 2020 University of Nevada, Las Vegas

Using Novel Mouse Knockout Models To Study The Roles Of Asm (Acid Sphingomyelinase) In The Regulation Of Multiple Stem Cell Compartments In Vivo, Amro Abdalla

UNLV Theses, Dissertations, Professional Papers, and Capstones

Acid Sphingomyelinase (ASM) is a lipid-modifying enzyme that breaks down sphingomyelin lipids into ceramide and phosphorylcholine. Genetic mutations in the human ASM gene leads to Niemann pick diseases (NPD) type A & B. In NPD type A, patients die between 1-2 years old due to severe neurological complications, while NPD type B patients live to adulthood but suffer from severe visceral organ complications. Type A is usually associated with complete inactivation of the ASM gene. The hallmark of NPD is Purkinje neuron (PN) death. PNs, the major neurons in the cerebellum part of the brain, regulate the balance and fine …


A Novel Role For Rassf1a In The Regulation Of Ras Activation., Desmond Ramón Harrell Stewart 2020 University of Louisville

A Novel Role For Rassf1a In The Regulation Of Ras Activation., Desmond Ramón Harrell Stewart

Electronic Theses and Dissertations

Ras is the most frequently activated oncogene in human cancer. It is not only the most frequently mutated oncogene, but is also rendered hyperactive in the wild-type form by aberrant regulation. Ras drives transformation and contributes to tumor aggressiveness by activating multiple downstream mitogenic effectors. Ras also possesses the paradoxical ability to induce apoptosis and senescence. Ras-induced apoptosis is not well understood, but has been largely attributed to the RASSF tumor suppressors, particularly RASSF1A. RASSF1A mediates Ras-induced apoptosis by activating pro-apoptotic proteins such as the MST kinases and BAX. RASSF1A is among the most frequently inactivated tumor suppressors in human …


Non-Invasive Tests For The Detection Of Nasopharyngeal Carcinoma, Mohan Sivanesan Vijaya 2020 Universiti Malaya

Non-Invasive Tests For The Detection Of Nasopharyngeal Carcinoma, Mohan Sivanesan Vijaya

Student Works (2020-2029)

Nasopharyngeal carcinoma (NPC) is a malignancy that arises in the epithelium of the nasopharynx. Diagnosis is often delayed due to inaccessibility of primary tumour site which leads to inaccurate biopsy. The pathogenesis of NPC is linked to the Epstein-Barr virus (EBV) and studies have shown the employability of plasma EBV DNA for the detection and monitoring of NPC. MicroRNAs (miRNA) are a class of small non-coding RNA that are dysregulated in various cancers and have been extensively studied as biomarker due to their stability in various biospecimens. The aim of this project is to evaluate the load of EBV DNA …


Differentiation Propensity, Safety, And Therapeutic Potential Of Mesenchymal Stem Cells Of Dental Origin, Musa Sabri 2020 Universiti Malaya

Differentiation Propensity, Safety, And Therapeutic Potential Of Mesenchymal Stem Cells Of Dental Origin, Musa Sabri

Student Works (2020-2029)

Introduction: A new area in medical research has emerged with the discovery of mesenchymal stem cells (MSCs) and their ability to differentiate into other cell types. Specifically, these cells are found in various tissues and have been utilized in the field of regenerative medicine to support tissue repair as well as in cell replacement. Lately, MSCs of dental origin have been the main players used for regenerative purposes although subtle differences based on their tissue source separate them. Objectives: This study aims to determine the differential propensity, safety, and potential therapeutic applications of dental-derived MSCs. This involves examining various aspects …


Artificial Intron Technology To Generate Conditional Knock-Out Mice, Amber N. Thomas-Gordon 2020 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Artificial Intron Technology To Generate Conditional Knock-Out Mice, Amber N. Thomas-Gordon

Dissertations and Theses (Open Access)

Genetic engineering has been re-shaped by the invention of new tools in modern biotechnology in a way that offers precision and efficiency in modifying the genome at a single nucleotide level and/or allowing precise control of gene expression. Such gene manipulation brings about significant findings and revelations in comprehending more about embryonic development, cellular and physiological functions, and disease pathology. Current methods used to produce conditional knockouts have limitations on conditional allele placement and modification varies among genes in different organisms. Thus, a system for generating conditional alleles with fidelity remains a challenge. My goal was to examine an approach …


The Investigation Of Group 1 Late Embryogenesis Abundant Protein 6 And Its Role In Arabidopsis Thaliana Desiccation Tolerance, Joann Eise Thomson 2020 Grand Valley State University

The Investigation Of Group 1 Late Embryogenesis Abundant Protein 6 And Its Role In Arabidopsis Thaliana Desiccation Tolerance, Joann Eise Thomson

Masters Theses

Like most seeds, Arabidopsis thaliana seed development is divided into three major phases: morphogenesis, storage deposition, and maturation drying. During maturation drying the seed becomes desiccation tolerant (DT) at some point and the seed rapidly loses water until its moisture level is approximately 10% on a fresh weight basis. The ability of the seeds to withstand this extreme water loss is hypothesized to be due, in part, to the accumulation of late embryogenesis abundant (LEA) proteins. In A. thaliana, there are 51 LEA proteins which are divided into seven groups based on amino acid sequence similarities. Group 1 LEA …


Putative Roles Of Cd200 In The Leukemogenesis And Immune Evasion Of Leukemia Stem Cells, Shelley Herbrich 2020 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Putative Roles Of Cd200 In The Leukemogenesis And Immune Evasion Of Leukemia Stem Cells, Shelley Herbrich

Dissertations and Theses (Open Access)

Acute myeloid leukemia (AML) stem cells (LSC) are capable of surviving current standard chemotherapy and are the likely source of deadly, relapsed disease. While stem cell transplant serves as proof-of-principle that AML LSCs can be eliminated by the immune system, the translation of existing immunotherapies to AML have been met with limited success. Consequently, understanding and exploiting the unique immune mechanisms of AML LSCs is critical. To identify novel immunotherapeutic targets, we sourced multiple large, publicly available datasets and identified CD200 as a potential stem-cell specific immune checkpoint in AML. We hypothesized that CD200 was a stem-cell specific mechanism of …


Aging, Gait Variability, And Adaptability, Collin Douglas Bowersock 2020 Old Dominion University

Aging, Gait Variability, And Adaptability, Collin Douglas Bowersock

Health Services Research Dissertations

The purpose of this work was to study the relationships between age, measures of gait variability, and locomotor adaptability. Measures of gait variability are used to identify maladapted locomotor behavior, motor disease, and risk of falls. The first aim was to determine the relationships between age and measures of gait variability. Thirty-four participants (23-71 years old) walked on a treadmill for 6 minutes at their preferred speed. Variability of stride times and lengths was computed via linear measures (standard deviation and coefficient of variation) and nonlinear measures (sample entropy and detrended fluctuation analysis). Movement trajectory variability of the dominant knee …


Comparative Analysis Of Small Non-Coding Rna And Messenger Rna Expression In Somatic Cell Nuclear Transfer And In Vitro-Fertilized Bovine Embryos During Early Development Through The Maternal-To-Embryonic Transition, Jocelyn Marie Cuthbert 2020 Utah State University

Comparative Analysis Of Small Non-Coding Rna And Messenger Rna Expression In Somatic Cell Nuclear Transfer And In Vitro-Fertilized Bovine Embryos During Early Development Through The Maternal-To-Embryonic Transition, Jocelyn Marie Cuthbert

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Cloning animals using somatic cell nuclear transfer (scNT) was first successfully demonstrated with the birth of Dolly the sheep, but the process of cloning remains highly inefficient. By improving our understanding of the errors that may occur during cloned cattle embryo development, we could obtain a greater understanding of how specific molecular events contribute to successful development. The central dogma of biology refers to the process of DNA being transcribed into messenger RNA (mRNA) and the translation of mRNA into proteins, which ultimately carry out the functions encoded by genes. The epigenetic code is defined as the array of chemical …


The Role Of Homologous Cyclin B’S In The Cell Cycle And, In Their Absence, The Effect On Zebrafish Early Development, Tetiana Petrachkova 2020 Western Michigan University

The Role Of Homologous Cyclin B’S In The Cell Cycle And, In Their Absence, The Effect On Zebrafish Early Development, Tetiana Petrachkova

Dissertations

Regulation of cell division is essential for normal embryo development. The Cyclins and their Cyclin-dependent kinases are key regulators controlling this process. In this thesis, I examine the role of cyclin B1 and cyclin B2 in zebrafish development. It is thought that both Cyclins are necessary for a cell to progress past the G2/M checkpoint into mitosis. First, I show that zygotic Cyclin B1 is essential for normal cell cycle progression, but not for cells to enter mitosis. Lack of zygotic Cyclin B1 in the early arrest mutant specter, which carries a nonsense mutation in the cyclin B1 gene, …


Uplc-Ms/Ms Analysis Of Cyp1a-Mediated Ethoxyresorufin-O-Deethylation Activity In The Rat Kidney Microsomes, Devaraj Venkatapura Chandrashekar, Reza Mehvar 2020 Chapman University

Uplc-Ms/Ms Analysis Of Cyp1a-Mediated Ethoxyresorufin-O-Deethylation Activity In The Rat Kidney Microsomes, Devaraj Venkatapura Chandrashekar, Reza Mehvar

Pharmacy Faculty Articles and Research

Ethoxyresorufin (ER)-O-deethylation (EROD) activity has been widely used to assess cytochrome P450 1A (CYP1A) activity. The kinetics of CYP1A activity have been well characterized in the liver microsomes. However, studies in kidney microsomes are limited due to the much lower EROD activity in this organ. Here, we developed and validated a sensitive UPLC-MS/MS assay for the characterization of the EROD activity in the rat kidney microsomes. In a 50 µL reaction mixture, rat kidney microsomes (0.25 mg/mL) were incubated with ER (0.1–5 µM) and NADPH (1 mM) for 10 min. Acidic solvents, such as trichloroacetic acid or formic …


Inhibition Of Hdac1/2 Along With Trap1 Causes Synthetic Lethality In Glioblastoma Model Systems, Trang T. T. Nguyen, Yiru Zhang, Enyuan Shang, Chang Shu, Catarina M. Quinzii, Mike-Andrew Westhoff, Georg Karpel-Massler, Markus D. Siegelin 2020 Columbia University

Inhibition Of Hdac1/2 Along With Trap1 Causes Synthetic Lethality In Glioblastoma Model Systems, Trang T. T. Nguyen, Yiru Zhang, Enyuan Shang, Chang Shu, Catarina M. Quinzii, Mike-Andrew Westhoff, Georg Karpel-Massler, Markus D. Siegelin

Publications and Research

The heterogeneity of glioblastomas, the most common primary malignant brain tumor, remains a significant challenge for the treatment of these devastating tumors. Therefore, novel combination treatments are warranted. Here, we showed that the combined inhibition of TRAP1 by gamitrinib and histone deacetylases (HDAC1/HDAC2) through romidepsin or panobinostat caused synergistic growth reduction of established and patient-derived xenograft (PDX) glioblastoma cells. This was accompanied by enhanced cell death with features of apoptosis and activation of caspases. The combination treatment modulated the levels of pro- and anti-apoptotic Bcl-2 family members, including BIM and Noxa, Mcl-1, Bcl-2 and Bcl-xL. Silencing of Noxa, BAK and …


Allosteric Regulation At The Crossroads Of New Technologies: Multiscale Modeling, Networks, And Machine Learning, Gennady M. Verkhivker, Steve Agajanian, Guang Hu, Peng Tao 2020 Chapman University

Allosteric Regulation At The Crossroads Of New Technologies: Multiscale Modeling, Networks, And Machine Learning, Gennady M. Verkhivker, Steve Agajanian, Guang Hu, Peng Tao

Mathematics, Physics, and Computer Science Faculty Articles and Research

Allosteric regulation is a common mechanism employed by complex biomolecular systems for regulation of activity and adaptability in the cellular environment, serving as an effective molecular tool for cellular communication. As an intrinsic but elusive property, allostery is a ubiquitous phenomenon where binding or disturbing of a distal site in a protein can functionally control its activity and is considered as the “second secret of life.” The fundamental biological importance and complexity of these processes require a multi-faceted platform of synergistically integrated approaches for prediction and characterization of allosteric functional states, atomistic reconstruction of allosteric regulatory mechanisms and discovery of …


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