Cellular and Molecular Physiology Commons^™

Functional Analysis Of Fam83d And Dupd1 – Two Novel Neruogenic Skeletal Muscle Atrophy-Induced Genes, Lisa Michelle Cooper

UNF Graduate Theses and Dissertations

Fam83d and Dupd1 have been identified as novel genes in skeletal muscle that are upregulated in response to neurogenic atrophy in a mouse model. qPCR analysis reveaed both genes are expressed in skeletal muscle with Fam83d expression being highest during myoblast proliferation, while Dupd1 expression is highest during myotube differentiation. Overexpression of either protein results in inhibition of proper muscle cell differentiation as evidenced by repression of both myosin heavy chain and myogenin expression. Characterization of transcriptional activity revealed both genes are modulated by myogenic regulatory factors and additionally, Dupd1 expression is enhanced by dexamethasone treatment. Assessment of subcellular localization …

A Dedicated Chaperone Mediates The Safe Transfer Of Mitoribosomal Proteins To Their Site Of Assembly, Gabrielle Ashley Hillman

Graduate School of Biomedical Sciences Theses and Dissertations

Mitochondrial ribosomes are functionally specialized for the synthesis of several essential inner membrane proteins of the respiratory chain. While remarkable progress has recently been made towards understanding the structure of mitoribosomes, the unique pathways and factors that facilitate their biogenesis remain largely unknown. This dissertation defines the physiological role of an evolutionarily conserved yeast protein called Mam33 in mitochondrial ribosome assembly. The biomedical relevance of this finding stems from the fact that mutations or changes in its expression of the human ortholog p32 result in mitochondrial dysfunction. In human patients, bi-allelic mutations cause severe multisystemic defects in mitochondrial energy metabolism, …

Insight Into Translational Activation In Yeast Mitochondria, Julia Lynn Jones

Graduate School of Biomedical Sciences Theses and Dissertations

Mitochondrial function depends on over a thousand proteins, of which the majority are nuclear DNA-encoded and approximately one percent are mitochondrial DNA-encoded. The mitochondrial DNA of Saccharomyces cerevisiae contains eight protein-encoding genes, seven of which are required for proper function of the respiratory complexes and one encodes a ribosomal protein. The bigenomic nature of the oxidative phosphorylation complexes requires coordinated expression and regulation from both the nuclear and the mitochondrial genomes. It is currently unclear how this regulatory network operates. However, it is thought that nuclear genome-encoded messengers localized to the mitochondria aid in this coordination.

A family of proteins …

Grapevine Vein Clearing Virus: Epidemiological Patterns And Construction Of A Clone, Cory Von Keith

Graduate Theses/Dissertations

Grapevine vein clearing virus (GVCV) is a recently discovered virus belonging to the Badnavirus genus. Characteristic to its name, the virus is associated with a disease where symptoms manifest as pronounced vein-clearing, resulting in severe berry deformation and vine decline in susceptible grape varieties. Sustainable production of wine is dependent on healthy plants. The associated disease is mainly found in Midwest vineyards. Attempts were made in this thesis to provide evidence of causality of the virus to the associated disease and to infer the historical path and migration pattern of GVCV. Conclusions and discussions will provide grape producers with the …

Identifying Kif Subtype That Mediates Axonal Targeting Of Kv7 Channels, Allison Houghton, Jennifer Walters, Mary Hong, Dhruv Joshi, Hee Jung Chung

PRECS 2018

Early-onset Benign Familial Neonatal Epilepsy (BFNE) and Epileptic Encephalopathy (EE), are associated with mutations in neuronal KCNQ/Kv7 channel subunits Kv7.2 and Kv7.3. Kv7 channels are voltage-dependent potassium channels. Enriched at the axonal plasma membrane, they pump potassium ions out of the neurons and inhibit repetitive or burst firing of action potentials. A single neuronal Kv7 channel is a heterotetramer composed of two Kv7.2 and two Kv7.3 subunits. BFNE and EE mutations in Kv7.2 and Kv7.3 lead to decreased surface expression along the axon, which means less potassium ions are moved across the axonal membrane where action potentials are generated and …

Till Death Do Us Part: The Marriage Of Autophagy And Apoptosis., Katrina F Cooper

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Autophagy is a widely conserved catabolic process that is necessary for maintaining cellular homeostasis under normal physiological conditions and driving the cell to switch back to this status quo under times of starvation, hypoxia, and oxidative stress. The potential similarities and differences between basal autophagy and stimulus-induced autophagy are still largely unknown. Both act by clearing aberrant or unnecessary cytoplasmic material, such as misfolded proteins, supernumerary and defective organelles. The relationship between reactive oxygen species (ROS) and autophagy is complex. Cellular ROS is predominantly derived from mitochondria. Autophagy is triggered by this event, and by clearing the defective organelles effectively, …

Pyruvate Kinase Isoform M2 Influences Autophagy And Related Processes In Hepatocellular Carcinoma Cells, Matthew Lin

University Scholar Projects

Hepatocellular carcinoma (HCC) is the most common form of liver cancer that affects ~14 million people in the world. Like all cancers, HCC is a disease that arises from unstinted cellular growth initiated by genetic alterations, metabolic changes, and dysregulation in key cellular pathways. Of interest is the relationship between metabolism and cell proliferation/degradation for therapeutic targeting. Pyruvate kinase M2 is a dimeric, glycolytically inactive isoform of the final enzyme involved in glycolysis, that is often upregulated in cancerous tissue. It is thought that the enzymatic function of PKM2 outside of glycolysis contributes to the biosynthesis of anabolic intermediates used …

Determination Of Adamts13 Susceptibility In Type Iia Von Willebrand Disease, Monica Buselli

Dissertations, Masters Theses, Capstones, and Culminating Projects

von Willebrand Disease (vWD) is a bleeding disorder caused by a deficiency in von Willebrand Factor (vWF), a large glycoprotein that assists in coagulation. Specifically, large vWF multimers in the blood stream are key components in starting the coagulation cascade. vWF is cleaved by the metalloprotease ADAMTS13, regulating the multimers size, which hinders vWF’s ability to function properly. The three main types of vWD —Type I, II, and III— are not well defined, and as a result are all similarly treated with plasma-derived vWF replacement therapy. Plasma-derived vWF is a treatment that does not cure the problem but relieves the …

Regulation Of The Tubulin Homolog Ftsz In Escherichia Coli, Monika S. Buczek

Dissertations, Theses, and Capstone Projects

Escherichia coli is a well-known pathogen, and importantly, a widely used model organism in all fields of biological sciences for cloning, protein purification, and as a model for Gram-negative bacterial species. And yet, researchers do not fully understand how this bacterium replicates and divides. Every year additional division proteins are discovered, which adds complexity to how we understand E. coli undergoes cell division. Due to their specific roles in cytokinesis, some of these proteins may be potential targets for development of antibacterials or bacteriostatics, which are much needed for fighting the current global antibacterial deficit. My thesis work focuses on …

Characterization Of The Roles Of Muscle-Synthesized Brain-Derived Neurotrophic Factor And Presynaptic Tyrosine Receptor Kinase B In Motor Neuron Axonal Transport, Luke A. Vanosdol

All NMU Master's Theses

Brain-derived neurotrophic factor (BDNF) is a small, diffusible protein essential for the development and function of neurons. It is synthesized by many types of tissue, including muscle. BDNF actions are mediated via binding to its receptor, tyrosine receptor kinase B (TrkB). The BDNF-TrkB complex is endocytosed into a specialized vesicle, which induces downstream signaling cascades locally in the dendrites, or, more often, is delivered to the cell soma via retrograde axonal transport, where it modulates gene expression. BDNF activation of TrkB is critical for the initiation of axonal transport, and this cellular process relies on the interaction of numerous adaptor …

Mrub_1325, Mrub_1326, Mrub_1327, And Mrub_1328 Are Orthologs Of B_3454, B_3455, B_3457, B_3458, Respectively Found In Escherichia Coli Coding For A Branched Chain Amino Acid Atp Binding Cassette (Abc) Transporter System, Bennett Tomlin, Adam Buric, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

In this project we investigated the biological function of the genes Mrub_1325, Mrub_1326, Mrub_1327, and Mrub_1328 (KEGG map number 02010). We predict these genes encode components of a Branched Chain Amino Acid ATP Binding Cassette (ABC) transporter: 1) Mrub_1325 (DNA coordinates 1357399-1358130 on the reverse strand) encodes the ATP binding domain; 2) Mrub_1326 (DNA coordinates 1358127-1359899 on the reverse strand) encodes the ATP-binding domain and permease domain; 3) Mrub_1327 (DNA coordinates 1359899-1360930 on the reverse strand) encodes a permease domain; and 4)Mrub_1328 (DNA coordinates 1711022-1712185 on the reverse strand) encodes the substrate binding domain. This system is not predicted to …

Confirmation That Mrub_1751 Is Homologous To E. Coli Xylf, Mrub_1752 Is Homologous To E. Coli Xylh, And Mrub_1753 Is Homologous To E. Coli Xylg, Ben Price, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

In this project we investigated the biological function of the genes Mrub_1751, Mrub_1752 and Mrub_1753 (KEGG map number 02010). We predict these genes encode components of a D-xylose ATP Binding Cassette (ABC) transporter: 1) Mrub_1752 (DNA coordinates 1809004-1810224 on the forward strand) encodes the permease component (aka transmembrane domain), predicted to be an ortholog and 2) Mrub_1753 (DNA coordinates 1810227-1811000 on the forward strand) encodes the ATP-binding domain (aka nucleotide binding domain); and 3) Mrub_1751 (DNA coordinates 1807855-1808892 on the forward strand) encodes the solute binding protein. The ABC-transporter for M. ruber to transport D-xylose is homologous with the transporter …

Estimating The Heritability Of Thermal Tolerance In Acropora Cervicornis And The Physiological Basis Of Adaptation That Correlates To Survival At Elevated Temperatures, Kelsey L. Yetsko

UNF Graduate Theses and Dissertations

Human activities have substantially increased the atmospheric concentrations of greenhouse gases, resulting in warmer ocean temperatures that are having a negative impact on reef corals, which are highly susceptible to changes in temperature. Understanding the degree to which species vary in their tolerance to elevated temperatures and whether this variation is heritable is important in determining their ability to adapt to climate change. In order to address this, Acropora cervicornis fragments from 20 genetically distinct colonies were kept at either ambient or elevated temperatures, and mortality was monitored for 26 days. Heritability of thermal tolerance was estimated using a clonal …

Serine-Dependent Sphingolipid Synthesis Is A Metabolic Liability Of Aneuploid Cells, Sunyoung Hwang, H. Tobias Gustafsson, Ciara O’Sullivan, Gianna Bisceglia, Xinhe Huang, Christian Klose, Andrej Schevchenko, Robert C. Dickson, Paola Cavaliere, Noah Dephoure, Eduardo M. Torres

Molecular and Cellular Biochemistry Faculty Publications

Aneuploidy disrupts cellular homeostasis. However, the molecular mechanisms underlying the physiological responses and adaptation to aneuploidy are not well understood. Deciphering these mechanisms is important because aneuploidy is associated with diseases, including intellectual disability and cancer. Although tumors and mammalian aneuploid cells, including several cancer cell lines, show altered levels of sphingolipids, the role of sphingolipids in aneuploidy remains unknown. Here, we show that ceramides and long-chain bases, sphingolipid molecules that slow proliferation and promote survival, are increased by aneuploidy. Sphingolipid levels are tightly linked to serine synthesis, and inhibiting either serine or sphingolipid synthesis can specifically impair the fitness …

The Role Of T-Box Proteins In Vertebrate Germ Layer Formation And Patterning, Sushma Teegala

Dissertations, Theses, and Capstone Projects

All of the tissues in triploblastic organisms, with the exception of the germ cells, arise from the three germ layers, ectoderm, mesoderm and the endoderm. The identification of the genes that underlie the differentiation of these layers is crucial to our understanding of development. T-box family proteins are DNA-binding transcriptional regulators that play important roles during germ layer formation in the early vertebrate embryo. Well-characterized members of this family, including the transcriptional activators Brachyury and VegT, are essential for the proper formation of mesoderm and endoderm, respectively. To date, T-box proteins have not been shown to play a role in …

Molecular Mechanisms Of Dna Replication Initiation In Hpvs With Genetic Variations Leading To Cellular Carcinogenesis, Gulden Yilmaz

Graduate School of Biomedical Sciences Theses and Dissertations

Human papillomaviruses are a vast family of double-stranded DNA viruses containing non-carcinogenic and carcinogenic types, whose crucial differences remain unknown, except for the difference in the frequency of DNA replication. The human papillomavirus (HPV) E2 protein regulates the initiation of viral DNA replication and transcription. Its recognition and binding to four 12 bp palindromic sequences in the viral origin is essential for its function. Little is known about the DNA binding mechanism of the E2 protein found in HPV types that have low risk for oncogenicity (low-risk) as well as the roles of various elements of the individual binding sites. …

Chaperoning Ef Hands That Shape Calcium Response: Ncald, Hpca And S100b, Jingyi Zhang

Graduate School of Biomedical Sciences Theses and Dissertations

All organisms have an internal clock with a defined period between repetitions of activities. The period for circadian clock in human is 24.5 hours, while in mouse and rat, it is 23.5 hours. However, all organisms are forced to be in synchronization with their environment. A major environmental force that resets the internal clock to 24 hours is light. This phenomenon is defined as “light entrainment” or “phase-setting”. It is unclear how this entrainment process occurs. Studies from this laboratory indicate a role for two neuronal calcium sensor proteins: Neurocalcin  (NCALD) and S100B. For these two genes, mRNA as …

Girk2 And Gababr1 Downregulate In Response To Ttx As Girk2, Gababr1, And Gababr2 Are Not Affected By Bc Treatment, Staci E. Hammer, Amanda Weiss, Hee Jung Chung

PRECS student projects

Homeostatic plasticity is the response neurons undergo to regulate changes in excitability levels and bring the cells back to homeostasis. Research on homeostatic plasticity at the molecular level can lead to improved treatments for neurological diseases such as epilepsy, Alzheimer's, and schizophrenia. The research featured in this poster looks at the response of GIRK (G protein-gated inwardly rectifying potassium) channels and GABAb (gamma-amniobutyric acid) receptors to neurotoxins, tetrodotoxin (TTX) or bicuculline (BC).

Prolonged activity blockade of 48 hour TTX treatment significantly reduced GABABR1 and GIRK2 expression. This supports the idea that because these two proteins inhibit action potentials, there will …

Patterns Of Morphological And Molecular Evolution In The Antillean Tree Bat, Ardops Nichollsi (Chiroptera: Phyllostomidae), Roxanne J. Larsen, Peter A. Larsen, Caleb D. Phillips, Hugh H. Genoways, Gary G. Kwiecinski, Scott C. Pedersen, Carleton J. Phillips, Robert J. Baker

University of Nebraska State Museum: Mammalogy Papers

Species endemic to oceanic islands offer unique insights into the mechanisms underlying evolution and have served as model systems for decades. Often these species show phenotypic variation that is correlated with the ecosystems in which they occur and such correlations may be a product of genetic drift, natural selection, and/or environmental factors. We explore the morphologic and genetic variation within Ardops nichollsi, a species of phyllostomid bat endemic to the Lesser Antillean islands. Ardops nichollsi is an ideal taxon to investigate the tempo of evolution in Chiroptera, as it: is a recently derived genus in the family Phyllostomidae; contains …

Differential Activity And Content Of High-Affinity Glutamate Transporters, Content Of Their Regulatory Proteins, And Capacity For Glutamine And Glutathione Synthesis In Tissues Of Finished Versus Growing Steers, Jing Huang

Theses and Dissertations--Animal and Food Sciences

Improvement of feeding regimens for production animals has been hindered by a lack of fundamental knowledge about how the capacity to regulate nutrient absorption across cell membranes affects the function of nutrient metabolizing enzymes. The objective is to determine if the activities and protein content of system X^-_AG glutamate transporter, its regulatory protein (GTRAP3-18 and ARL6IP1), glutamine synthetase (GS) and glutathione (GSH) content, changes in liver (Experiment 1), longissimus dorsi (LM) and subcutaneous adipose tissue (SF) (Experiment 2) as beef steers transitioned from predominantly-lean (growing) to -lipid (finished) tissue accretion phases. In liver (Experiment 1), system X^{- …}

The Role Of Creg1 As A Master Regulator Of Liver Function, Abdulrahman Siran Aldaghmi

Masters Theses

The liver is known as the chemical factory of the body because it performs a wide range of biochemical functions required for life. Since the liver has such an important role in regulation of normal physiological processes, liver diseases cause a high rate of morbidity and mortality. Therefore, understanding the mechanisms of liver development will shed light on the causes of liver disease. In this study, a cell line model that utilizes rat hepatoma cells (Fg14) and hepatoma variant cells (H11) was used to identify master regulators of liver gene expression. Whole genome expression studies identified the gene CREG1 (Cellular …

The Effect Of Transformed Escherichia Coli On The Mouse Intestine Microbiome: The Microbial Metabolic Enhancement Hypothesis, Bryar P. Kader

Senior Honors Theses

Metabolic disorders affect around thirty-four percent of the population in the United States. Among these disorders is lactose intolerance, which results from diminished production of the human lactase enzyme. This disorder and others like it are genetically determined and cannot be cured. However, the use of transformed bacteria implanted in the colon may provide a means by which the faulty pathway can be bypassed. To test whether transformed bacteria have the capability to aid in the digestion of normally indigestible compounds, a transformed strain of Escherichia coli overexpressing the beta-galactosidase enzyme encoded by the lacZ gene was colonized in the …

The Thioredoxin Trx-1 Regulates The Major Oxidative Stress Response Transcription Factor, Skn-1, In Caenorhabditis Elegans, Katie C. Mccallum

Dissertations and Theses (Open Access)

The ability to respond to hostile environmental conditions is critical for the survival of an organism. Oxidative stress is an adverse state in which reactive oxygen species (ROS) accumulate to a harmful level and, if left unresolved, can lead to cellular dysfunction and organismal disease. Sophisticated detoxification systems, characterized by a battery of enzymatic antioxidants, are utilized to neutralize ROS thereby reducing stress. However, ROS are also purposefully produced by designated cellular enzymes to facilitate the signaling and regulation of critical physiological processes. Therefore, both the production and neutralization of ROS must be tightly controlled. Indeed, the expression of detoxification …

Single Nucleotide Polymorphisms In Cldn14 And Smoc1 Affecting Bone Mineral Density Influence Other Musculoskeletal Traits, Christopher Payette, Courtney Sprouse, Cara Goerlich, Heather A. Gordish-Dressman, Thomas Lynch, Heather Flynn, Leticia M. Ryan, Eric P. Hoffman, Monica J. Hubal, Paul D. Thompson, Theodore J. Angelopoulos, Paul M. Gordon, Niall M. Moyna, Linda S. Pescatello, Paul S. Visich, Robert F. Zoeller, Laura L. Tosi

GW Research Days 2016 - 2020

Background: A recent genome-wide association study (GWAS) identified novel genes influencing bone mineral density (BMD). This three stage GWAS identified two novel loci: rs227425 in the SPARC-Related Modular Calcium Binding 1 gene (SMOC1) was significantly associated with BMD and rs170183 in the claudin 14 (CLDN14) gene was significantly associated with BMD in females.

Objective: The purpose of this study was to determine if two novel single nucleotide polymorphisms (SNPs) known to affect BMD are associated with other musculoskeletal traits.

Methods/Design :The Bone Health Cohort consists of 150 African-American participants enrolled at Children’s National Health System as part of …

A Mechanistic Study Of An Ipsc Model For Leigh’S Disease Caused By Mtdna Mutataion (8993 T>G), John P. Galdun

Theses and Dissertations

Mitochondrial diseases encompass a broad range of devastating disorders that typically affect tissues with high-energy requirements. These disorders have been difficult to diagnose and research because of the complexity of mitochondrial genetics, and the large variability seen among patient populations. We have devised and carried out a mechanistic study to generate a cell based model for Leigh’s disease caused by mitochondrial DNA mutation 8993 T>G. Leigh’s disease is a multi-organ system disorder that depends heavily on the mutation burden seen within various tissues. Using new reprogramming and sequencing technologies, we were able to show that Leigh’s disease patient fibroblasts …

P53: "The Wall Watcher", Nektarios Barabutis, John D. Catravas

Bioelectrics Publications

No abstract provided.

Multi-Stress Proteomics: The Global Protein Response To Multiple Environmental Stressors In The Porcelain Crab Petrolisthes Cinctipes, Michael A. Garland

Master's Theses

Global climate change is increasing the number of hot days along the California coast as well as increasing the incidence of off-shore upwelling events that lower the pH of intertidal seawater; thus, intertidal organisms are experiencing an increase in more than one stress simultaneously. This study seeks to characterize the global protein response of the eurythermal porcelain crab Petrolisthes cinctipes to changes in thermal, pH, and tidal regime treatments, either combined or individually. The first experiment examined temperature stress alone and sought to determine the effect of chronic temperature acclimation on the acute heat shock response. We compared the proteomic …

Hippocalcin Response To Calcium: Do Conserved Tryptophans – W30 Or W103 – Matter?, Sunkesula K. Sagar

Graduate School of Biomedical Sciences Theses and Dissertations

Changes in intracellular calcium levels play a very important role in cell signaling, in turn, affecting neuronal functions such as memory, learning and cell death. A class of proteins called Neuronal Calcium Sensor (NCS) proteins serves to modulate the functioning of the neuronal cells in response to changes in calcium levels, and prevent neuronal apoptosis. Structurally, all NCS proteins have 4 calcium-binding EF hand motifs, although EF1 does not bind to calcium in many members. All NCS proteins have an acyl modification at the N- terminus – where a myristoyl group is added post-translationally. Hippocalcin (HPCA) is an NCS protein, …

The Proteomic Response In The Crustacean Molting Gland Of Land Crab Gecarcinus Lateralis In Response To Artificially Induced Molting Throughout Its Molting Cycle., Andrea Reider, Talia B. Head, Lars Tomanek, Donald L. Mykles

STAR Program Research Presentations

Molting in crustaceans is a highly complex physiological process involving negative regulation by two paired endocrine glands, the X-organ/sinus gland complex (XO/SG) and the Y-organ (YO). The XO/SG complex is responsible for making molt-inhibiting hormone (MIH) which negatively regulates synthesis of molting hormones (ecdysteroids) by the YO. Eyestalk ablation (ESA) removes the source of MIH and provides an experimental means to manipulate and induce molting, although the physiological effects of ESA on the YO have not been fully characterized. Analysis of gene expression in the XOs and YOs has lead to the development of a proposed molecular signaling pathway which …

Med13p Prevents Stress-Independent Mitochondrial Hyperfragmentation And Aberrant Apoptosis Activation In Saccharomyces Cerevisiae By Controlling Cyclin C Nuclear Localization, Svetlana Khakhina

Graduate School of Biomedical Sciences Theses and Dissertations

During aging, and as a result of environmental changes, cells are exposed to elevated levels of reactive oxygen species (ROS). High ROS levels induce lipid oxidation, protein aggregation, mitochondrial hyperfragmentation, DNA damage and programmed cell death (PCD), also called apoptosis. PCD is a highly regulated process and its misregulation has been linked to neurodegenerative diseases and cancer development.

Our hypothesis is that cyclin C plays a role in the initiation of apoptosis. During normal conditions, cyclin C represses the transcription of stress response genes (SRG). In response to stress, cyclin C translocates to the cytoplasm where it facilitates mitochondrial hyperfragmentation …