Egfr Signaling From The Early Endosome.,
2018
University of Louisville
Egfr Signaling From The Early Endosome., Julie A. Gosney
Electronic Theses and Dissertations
The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is an integral component of proliferative signaling. When activated by a ligand at the plasma membrane, EGFR dimerizes with another ErbB family receptor, leading to kinase domain activation and transphosphorylation of C-terminus tyrosine residues. These phosphotyrosines act as crucial regulators of EGFR signaling as effector proteins dock to the receptor at these sites. The receptor undergoes clathrin-mediated endocytosis into early endosomes, where it can then be trafficked to a lysosome for degradation. However, the kinase domain of EGFR retains its activity during trafficking, suggesting that EGFR can continue …
Unfolded Protein Response Pathways In Skeletal Muscle Homeostasis.,
2018
University of Louisville
Unfolded Protein Response Pathways In Skeletal Muscle Homeostasis., Kyle R. Bohnert
Electronic Theses and Dissertations
Skeletal muscle mass, contractile properties, and metabolic function are regulated through the coordinated activation of multiple intracellular signaling pathways and genetic reprogramming. The endoplasmic reticulum (ER) plays a pivotal role in protein folding and calcium homeostasis in many cell types, including skeletal muscle. Disruption of calcium levels or accumulation of misfolded proteins in the ER lumen leads to stress, which results in the activation of a signaling network called the unfolded protein response (UPR). Further, recent studies have suggested that in certain conditions, UPR pathways can be activated independent of ER stress. However, the role of ER stress and the …
Effect Of Morinda Citrifolia (Noni)-Enriched Diet On Hepatic Heat Shock Protein And Lipid Metabolism-Related Genes In Heat Stressed Broiler Chickens,
2018
University of Arkansas, Fayetteville
Effect Of Morinda Citrifolia (Noni)-Enriched Diet On Hepatic Heat Shock Protein And Lipid Metabolism-Related Genes In Heat Stressed Broiler Chickens, Joshua Flees
Graduate Theses and Dissertations
Heat stress (HS) has been reported to alter fat deposition in broilers, however the underlying molecular mechanisms are not well-defined; therefore, the objectives of the current study were to: (1) determine the effects of acute (2 h) and chronic (3 wk) HS on the expression of key molecular signatures involved in hepatic lipogenic and lipolytic programs; and (2) assess if diet supplementation with dried Noni medicinal plant (0.2% of the diet) modulates these effects. Broilers (n=480 males, 1 d) were randomly assigned to 12 environmental chambers, subjected to two environmental conditions (HS at 35°C vs. thermoneutral condition [TN] at 24°C) …
Dissecting The Mechanism Of Action Of A Novel Antifungal Peptide,
2018
University of Arkansas, Fayetteville
Dissecting The Mechanism Of Action Of A Novel Antifungal Peptide, Cody Bullock
Graduate Theses and Dissertations
There is an urgent need for novel treatments for Candida infections. The utility of antimicrobial peptides for antifungal therapy has garnered interest in recent years. One promising family of peptides is the Histatins, a family of naturally-occurring peptides secreted into the oral cavity that display antimicrobial activity. Histatin 5 is a twenty-four amino acid peptide with strong antifungal activity. Studies from our laboratory have identified a small histatin-derived peptide, KM29, that yields fungicidal activity 10-fold greater than Histatin 5 against multiple Candida species. Our laboratory has focused on understanding the mechanism of action of KM29 to further develop it as …
Conformationally-Controlled Late-Stage Modifications For Sar Studies Of The C-3-Glcp Moiety Of Ipomoeassin F,
2018
University of Arkansas, Fayetteville
Conformationally-Controlled Late-Stage Modifications For Sar Studies Of The C-3-Glcp Moiety Of Ipomoeassin F, Lucas Whisenhunt
Graduate Theses and Dissertations
The resin glycoside, ipomoeassin F has been shown to be extremely potent against multiple cancer lines (IC50 = 4.2-36 nM). However, the mechanism of action of this potent and complex natural product is still not fully understood. The α,β-unsaturated esters of the glucosyl moiety have been shown to be vital for the overall cytotoxicity of ipomoeassin F. Nevertheless, the importance of the tigloyl ester of the glucosyl moiety is still largely unknown. This work aimed to study the pharmacophore importance of the tigloyl ester by creating, an efficient, scalable, and flexible synthesis route for various analogs. The 18-linear step synthesis …
The Role Of Rad4 In Dna Repair And Its Interplay With Telomeres In Tetrahymena Thermophila,
2018
Missouri State University
The Role Of Rad4 In Dna Repair And Its Interplay With Telomeres In Tetrahymena Thermophila, Emily Nischwitz
Graduate Theses/Dissertations
Telomeres are repetitive parts of the genome that act as a protective end cap to the chromosomes. Telomeres are critical to the integrity and stability of the genome, therefore, ensuring that their sequence is maintained, even after damage, is crucial. Much of the pioneering work responsible for explaining telomeres has been conducted in ciliates, specifically in Tetrahymena thermophila. Telomeres in T. thermophila have a high amount of tandem thymine repeats (GGGGTT) and, thus, are susceptible to ultraviolet light (UV) induced lesions called pyrimidine dimers, which must be repaired by nucleotide excision repair (NER). In humans, Xeroderma Pigmentosum C (XPC) …
Computational Analysis Of Genomic Variants Affecting Predicted Microrna:Target Interactions In Prostate Cancer.,
2018
Keck Graduate Institute, KGI
Computational Analysis Of Genomic Variants Affecting Predicted Microrna:Target Interactions In Prostate Cancer., Angélica Paola Hernández Pérez
KGI Theses and Dissertations
Prostate cancer (PCa) is the most common cancer of men in the United States and is third only to lung and colon as a cause of cancer death. Clinical behavior of the disease is variable and the combination of prostate-specific antigen (PSA) screening and Gleason score staging are currently the best available molecular and pathology tools to predict outcomes. Cancer biology research establishes microRNAs (miRNAs) as key molecular components in both normal and pathological states. Thus, elucidating miRNAs perturbed by genomic alterations will expand our understanding of the molecular taxonomy of PCa with the aim to complement current practices in …
“Do We Know Jack” About Jak? A Closer Look At Jak/Stat Signaling Pathway,
2018
Chapman University
“Do We Know Jack” About Jak? A Closer Look At Jak/Stat Signaling Pathway, Emira Bousoik, Hamidreza Montazeri Aliabadi
Pharmacy Faculty Articles and Research
Janus tyrosine kinase (JAK) family of proteins have been identified as crucial proteins in signal transduction initiated by a wide range of membrane receptors. Among the proteins in this family JAK2 has been associated with important downstream proteins, including signal transducers and activators of transcription (STATs), which in turn regulate the expression of a variety of proteins involved in induction or prevention of apoptosis. Therefore, the JAK/STAT signaling axis plays a major role in the proliferation and survival of different cancer cells, and may even be involved in resistance mechanisms against molecularly targeted drugs. Despite extensive research focused on the …
Pias-Family Proteins Negatively Regulate Glis3 Transactivation Function Through Sumo Modification In Pancreatic Β Cells,
2018
Murray State University
Pias-Family Proteins Negatively Regulate Glis3 Transactivation Function Through Sumo Modification In Pancreatic Β Cells, Tyler M. Hoard, Xiaoping Yang, Anton M. Jetten, Gary T. Zeruth Dr.
Faculty & Staff Research and Creative Activity
Gli-similar 3 (Glis3) is Krüppel-like transcription factor associated with the transcriptional regulation of insulin. Mutations within the Glis3 locus have been implicated in a number of pathologies including diabetes mellitus and hypothyroidism. Despite its clinical significance, little is known about the proteins and posttranslational modifications that regulate Glis3 transcriptional activity. In this report, we demonstrate that the SUMO-pathway associated proteins, PIASy and Ubc9 are capable of regulating Glis3 transactivation function through a SUMO-dependent mechanism. We present evidence that SUMOylation of Glis3 by PIAS-family proteins occurs at two conserved lysine residues within the Glis3 N-terminus and modification of Glis3 by SUMO …
Yeast: The Gateway To Redefining And Improving Biology Labs,
2018
Ursinus College
Yeast: The Gateway To Redefining And Improving Biology Labs, Connor Loomis
Biology Summer Fellows
Building off of collegiate research performed during the summer of 2018, this lesson plan outlines a lab for secondary students using yeast. Yeast is an affordable and convenient organism to introduce to secondary education, and students can learn a lot about biology through it. Essentially, the goal of the lab is for students to explore the effects of certain substances on the growth of yeast. While content is emphasized, this lesson plan also looks to build students’ understanding of science in general as well as proper laboratory skills and technique. In addition, it pushes students in their thinking as they …
A V-To-F Substitution In Sk2 Channels Causes Ca2+ Hypersensitivity And Improves Locomotion In A C. Elegans Als Model,
2018
Chapman University
A V-To-F Substitution In Sk2 Channels Causes Ca2+ Hypersensitivity And Improves Locomotion In A C. Elegans Als Model, Young-Woo Nam, Sabia N. Baskoylu, Dimitris Gazgalis, Razan Orfali, Meng Cui, Anne C. Hart, Miao Zhang
Pharmacy Faculty Articles and Research
Small-conductance Ca2+-activated K+ (SK) channels mediate medium afterhyperpolarization in the neurons and play a key role in the regulation of neuronal excitability. SK channels are potential drug targets for ataxia and Amyotrophic Lateral Sclerosis (ALS). SK channels are activated exclusively by the Ca2+-bound calmodulin. Previously, we identified an intrinsically disordered fragment that is essential for the mechanical coupling between Ca2+/calmodulin binding and channel opening. Here, we report that substitution of a valine to phenylalanine (V407F) in the intrinsically disordered fragment caused a ~6 fold increase in the Ca2+ sensitivity of SK2-a channels. This substitution resulted in a novel interaction between …
Developing Droplet Based 3d Cell Culture Methods To Enable Investigations Of The Chemical Tumor Microenvironment,
2018
University of New Mexico - Main Campus
Developing Droplet Based 3d Cell Culture Methods To Enable Investigations Of The Chemical Tumor Microenvironment, Jacqueline Alexandria De Lora
Biomedical Sciences ETDs
Adaptation of cancer cells to changes in the biochemical microenvironment in an expanding tumor mass is a crucial aspect of malignant progression, tumor metabolism, and drug efficacy. In vitro, it is challenging to mimic the evolution of biochemical gradients and the cellular heterogeneity that characterizes cancer tissues found in vivo. It is well accepted that more realistic and controllable in vitro 3D model systems are required to improve the overall cancer research paradigm and thus improve on the translation of results, but multidisciplinary approaches are needed for these advances. This work develops such approaches and demonstrates that new droplet-based cell-encapsulation …
Conservation Of Freshwater Live-Bearing Fishes: Development Of Germplasm Repositories For Goodeids,
2018
Louisiana State University and Agricultural and Mechanical College
Conservation Of Freshwater Live-Bearing Fishes: Development Of Germplasm Repositories For Goodeids, Yue Liu
LSU Doctoral Dissertations
Fishes of the family Goodeidae are considered to be among the most imperiled taxa in the world. The goal of this project was to provide a foundation for development of sperm repositories for goodeids and to use them as a model to assist conservation programs for imperiled freshwater live-bearing fishes. Development of such repositories is challenging because of unusual reproductive characteristics of live-bearing fishes, such as sperm bundles, internal fertilization, and the bearing of live young. Standardized methods were established to evaluate quality-related attributes of sperm bundles. The different features between activation of free and bundled sperm were investigated and …
Loss Of Marv1 Promotes Chop Signaling In Mouse Liver,
2018
Rowan University
Loss Of Marv1 Promotes Chop Signaling In Mouse Liver, Shad Anthony Mitchell
Graduate School of Biomedical Sciences Theses and Dissertations
Metabolic syndrome (MetS) is a term used to define a set of metabolic diseases: obesity, type 2 diabetes (T2D), hyperlipidemia, hypertension, nonalcoholic fatty liver disease (NAFLD), and nonalcoholic hepatosteatosis (NASH). Those with MetS have a higher incidence of cardiovascular disease and stroke. Current drug treatments for MetS treat the individual pathologies associated with the diseases, rather than directly targeting MetS as a whole. We hypothesize that the inhibition of a ubiquitous lipid transporter known as ARV1 can improve pathologies associated with MetS. To test this hypothesis, we utilized liver tissue from mARV1 knockout mice fed a high-fat diet and examined …
Anemarrhena Asphodeloides Bunge And Its Constituent Timosaponin‐Aiii Induce Cell Cycle Arrest And Apoptosis In Pancreatic Cancer Cells,
2018
University of South Florida
Anemarrhena Asphodeloides Bunge And Its Constituent Timosaponin‐Aiii Induce Cell Cycle Arrest And Apoptosis In Pancreatic Cancer Cells, Catherine B. Marelia, Arielle Sharp, Tiffany A. Shemwell, Y. C. Zhang, Brant R. Burkhardt
Molecular Biosciences Faculty Publications
Pancreatic cancer is one of the most recalcitrant and lethal of all cancers. We examined the effects of Anemarrhena asphodeloides (AA) and timosaponin‐AIII (TAIII), a steroidal saponin present in AA, on pancreatic cancer cell proliferation and aimed to elucidate their potential apoptotic mechanisms of action. Viability assays and cell cycle analysis revealed that both AA and TAIII significantly inhibited pancreatic cancer cell proliferation and cell cycle progression compared to treatment with gemcitabine, the standard chemotherapeutic agent for advanced pancreatic cancer. We identified a dose‐dependent increase in caspase‐dependent apoptosis and activation of pro‐apoptotic PI3K/Akt pathway proteins, with a subsequent downregulation of …
Dynamics And Interactions Of Membrane Proteins,
2018
Marquette University
Dynamics And Interactions Of Membrane Proteins, Azamat Galiakhmetov
Dissertations (1934 -)
Membrane proteins are members of the class of proteins that perform their functions while being associated with a lipid bilayer. In the cell, they serve as transporters, receptors, anchors and enzymes. The domain organisation of these proteins suggests importance of lipid membrane and protein-lipid interactions for protein function. The requirement of a membrane mimic and the level of its resemblance to a native one for protein investigation makes the studies of membrane proteins a challenging project. My research work is focusing on the biophysical and biochemical studies of membrane proteins. This dissertation outlines two separate projects, each with their own …
Strategies For The Modulation Of Protease Activated Receptors (Pars),
2018
Marquette University
Strategies For The Modulation Of Protease Activated Receptors (Pars), Disha M. Gandhi
Dissertations (1934 -)
Protease-activated receptors (PARs) are class A G protein-coupled receptors (GPCRs) with 4 subtypes (PAR 1 – 4) and with a unique mode of action. PARs are cleaved by extracellular proteases at the N-terminus, creating a new tethered ligand that activates the receptor and transduces biological signals into the cell. PARs have been implicated in various productive and pathological signals, including those related to thrombosis, inflammation, reperfusion injury, and cancer cell metastasis. Despite the fact that PARs are attractive as drug targets, their intramolecular mode of activation makes it challenging to modulate them with drugs in a selective manner, and only …
Exploring The Role Of Rna Polymerase Iii Complex Assembly On Ribosomal Dna Silencing In Saccharomyces Cerevisiae,
2018
Louisiana State University and Agricultural and Mechanical College
Exploring The Role Of Rna Polymerase Iii Complex Assembly On Ribosomal Dna Silencing In Saccharomyces Cerevisiae, Kyle Thomas Kern
LSU Doctoral Dissertations
The yeast rDNA region is host to a number of transcriptional regulatory elements, which work in conjunction to generate essential RNA subunits of ribosomes, as well as protecting the region from DNA damage. The role of RNA polymerase III complex binding at the 5S gene on rDNA silencing in the NTS2 region was investigated, both by use of a TY1:MET15 reporter insert and a MET15 gene integration at an endogenous SphI site. It was discovered that Pol III complexes do have an effect on reporter expression in the NTS2 region, though the specific effect was different based on the method …
Synthesis Of Interleukin 1 Beta And Interleukin 6 In Human Lymphocytes Is Stimulated By Tributyltin,
2018
Tennessee State University
Synthesis Of Interleukin 1 Beta And Interleukin 6 In Human Lymphocytes Is Stimulated By Tributyltin, Shyretha Brown, Mariam Boules, Nafisa Hamza, Xiaofei Wang, Margaret Whalen
Chemistry Faculty Research
Tributyltin (TBT) is a widespread environmental contaminant that is present in human blood and other tissues. It has been shown to disrupt the immune function of human natural killer (NK) cells and to alter the secretion of a number of pro-inflammatory cytokines from immune cells. Secretion of both interleukin 1β (IL-1β) and interleukin 6 (IL-6) from human lymphocytes can be increased dependent upon the level of TBT exposure. This study shows that the TBT-induced increases in secretion of both cytokines are due to TBT-induced increases in the synthesis of these proteins and not simply because of the release of pre-existing …
Efficient Intracellular Delivery Of Cell-Impermeable Cargo Molecules By Peptides Containing Tryptophan And Histidine,
2018
Chapman University
Efficient Intracellular Delivery Of Cell-Impermeable Cargo Molecules By Peptides Containing Tryptophan And Histidine, Amir Nasrolahi Shirazi, Saghar Mozaffari, Rinzhin Tshering Sherpa, Rakesh Tiwari, Keykavous Parang
Pharmacy Faculty Articles and Research
We have previously evaluated and reported numerous classes of linear and cyclic peptides containing hydrophobic and hydrophilic segments for intracellular delivery of multiple molecular cargos. Herein, a combination of histidine and tryptophan amino acids were designed and evaluated for their efficiency in intracellular delivery of cell-impermeable phosphopeptides and the anti-HIV drug, emtricitabine. Two new decapeptides, with linear and cyclic natures, both containing alternate tryptophan and histidine residues, were synthesized using Fmoc/tBu solid-phase chemistry. The peptides were characterized and purified by using matrix-assisted laser desorption/ionization (MALDI) spectroscopy and high-performance liquid chromatography (HPLC), respectively. These peptides did not show significant toxicity up …
