Functional Analysis Of The Replication Fork Proteome Identifies Bet Proteins As Pcna Regulators,
2019
Vanderbilt University
Functional Analysis Of The Replication Fork Proteome Identifies Bet Proteins As Pcna Regulators, Sarah R. Wessel, Kareem N. Mohni, Jessica W. Luzwick, Huzefa Dungrawala, David Cortez
Molecular Biosciences Faculty Publications
Identifying proteins that function at replication forks is essential to understanding DNA replication, chromatin assembly, and replication-coupled DNA repair mechanisms. Combining quantitative mass spectrometry in multiple cell types with stringent statistical cutoffs, we generated a high-confidence catalog of 593 proteins that are enriched at replication forks and nascent chromatin. Loss-of-function genetic analyses indicate that 85% yield phenotypes that are consistent with activities in DNA and chromatin replication or already have described functions in these processes. We illustrate the value of this resource by identifying activities of the BET family proteins BRD2, BRD3, and BRD4 in controlling DNA replication. These proteins …
P53 Phosphomimetics Preserve Transient Secondary Structure But Reduce Binding To Mdm2 And Mdmx,
2019
University of South Florida
P53 Phosphomimetics Preserve Transient Secondary Structure But Reduce Binding To Mdm2 And Mdmx, Robin Levy, Emily Gregory, Wade Borcherds, Gary W. Daughdrill
Molecular Biosciences Faculty Publications
The disordered p53 transactivation domain (p53TAD) contains specific levels of transient helical secondary structure that are necessary for its binding to the negative regulators, mouse double minute 2 (Mdm2) and MdmX. The interactions of p53 with Mdm2 and MdmX are also modulated by posttranslational modifications (PTMs) of p53TAD including phosphorylation at S15, T18 and S20 that inhibits p53-Mdm2 binding. It is unclear whether the levels of transient secondary structure in p53TAD are changed by phosphorylation or other PTMs. We used phosphomimetic mutants to determine if adding a negative charge at positions 15 and 18 has any effect on the transient …
Extracellular Matrix In Development And Disease,
2019
Boise State University
Extracellular Matrix In Development And Disease, Julia Thom Oxford, Jonathon C. Reeck, Makenna J. Hardy
Biomedical Research Institute Publications and Presentations
The evolution of multicellular metazoan organisms was marked by the inclusion of an extracellular matrix (ECM), a multicomponent, proteinaceous network between cells that contributes to the spatial arrangement of cells and the resulting tissue organization. The development of an ECM that provides support in larger organisms may have represented an advantage in the face of selection pressure for the evolution of the ECM.
The Role Of Klp-4 In Regulating Cholinergic Signaling In Vivo,
2019
Rollins College
The Role Of Klp-4 In Regulating Cholinergic Signaling In Vivo, Catherine Deuchler
Honors Program Theses
Cellular trafficking is dominated by the use of motor proteins trafficking cargo along the microtubules that make up the cellular cytoskeleton. Polarity within these cells controls the direction of the trafficking, and the cargo consists of organelles, new proteins, neurotransmitters, etc.. Motor proteins differ in the cargo they carry, the direction that they move, as well as the rate and distance that they can travel. The trafficking of neurotransmitters occurs along neurons, highly polarized cells, and this research focuses on neuronal trafficking as a method of controlling the release and degradation of acetylcholine and thus regulating the signals that they …
Identification Of Proteins Interacting With Zebrafish Miro Orthologs In The Yeast Two-Hybrid System,
2019
Rollins College
Identification Of Proteins Interacting With Zebrafish Miro Orthologs In The Yeast Two-Hybrid System, Yiran Tao
Honors Program Theses
The motility of mitochondria is required for providing energy and maintaining basic cellular functions in neurons. Mitochondrial Rho GTPase (Miro) is an essential component of the mitochondrial trafficking machinery, a protein complex that anchors mitochondria to the microtubule motor protein for long-distance transport. As a protein localizing to the mitochondrial outer membrane, Miro regulates the morphology and the motility of mitochondria. Upon mitochondrial depolarization, the PINK1/Parkin pathway is activated to arrest mitochondrial movement by targeting Miro for phosphorylation and ubiquitination in a calcium-sensitive manner. However, it remains unclear what effects the PINK1-dependent phosphorylation has on the structure and binding properties …
Seven Coordinate Molybdenum And Tungsten Complexes Containing Tpm And Tpm Derivatives And The Impact Of Ligand Substitution On Nmr Chemical Shifts,
2019
Butler University
Seven Coordinate Molybdenum And Tungsten Complexes Containing Tpm And Tpm Derivatives And The Impact Of Ligand Substitution On Nmr Chemical Shifts, Cole Seager
Undergraduate Honors Thesis Collection
A series of known and new seven coordinate molybdenum and tungsten complexes of tris(pyrazolyl)methane (Tpm) and substituted Tpm, [TpmM(CO)3X]+, have been synthesized. Depending on the identity of X, (bromo, iodo, hydrido) and the substitution of the Tpm ligand, substantial chemical shift differences are observed for the hydrogen on the central carbon of the Tpm ligand. Factors impacting the chemical shift of the hydrogen on the central carbon of the Tpm ligand, such as the electron donating ability of the Tpm ligand and the electronegativity of the additional ligand on the metal, will be discussed.
The Otud5–Ubr5 Complex Regulates Fact-Mediated Transcription At Damaged Chromatin,
2019
University of South Florida
The Otud5–Ubr5 Complex Regulates Fact-Mediated Transcription At Damaged Chromatin, Angelo De Vivo, University Of South Florida, Jose Yegres, Jeonghyeon Kim, Sylvia Emly, Younghoon Kee
Molecular Biosciences Faculty Publications
Timely stalling and resumption of RNA polymerases at damaged chromatin are actively regulated processes. Prior work showed an importance of FACT histone chaperone in such process. Here we provide a new role of OTUD5 deubiquitinase in the FACT-dependent process. Through a DUB RNAi screen, we found OTUD5 as a specific stabilizer of the UBR5 E3 ligase. OTUD5 localizes to DNA double strand breaks (DSBs), interacts with UBR5 and represses the RNA Pol II elongation and RNA synthesis. OTUD5 co-localizes and interacts with the FACT component SPT16 and antagonizes the histone H2A deposition at DSB lesions. OTUD5 interacts with UBR5 and …
Proteomics Of Carbon Fixation Energy Sources In Halothiobacillus Neapolitanus,
2019
Arkansas Tech University
Proteomics Of Carbon Fixation Energy Sources In Halothiobacillus Neapolitanus, Jonathan Hunter, Maria Marasco, Ilerioluwa Sowande, Newton P. Hilliard Jr.
Journal of the Arkansas Academy of Science
Through the use of proteomics, it was uncovered that the autotrophic, aerobic purple sulfur bacterium Halothiobacillus neapolitanus displays changes in cellular levels of portions of its carbon dioxide uptake and fixation mechanisms upon switch from bicarbonate to CO2(g) as carbon source. This includes an increase in level of a heterodimeric bicarbonate transporter along with a potential switch between form I and form II of RubisCO. Additional changes are seen in several sulfur oxidation pathways, which may indicate a link between sulfur oxidation pathways as an energy source and carbon uptake/fixation mechanisms.
Wetland Biogeochemical Responses To Predicted Climate Change Scenarios,
2019
Georgia Southern University
Wetland Biogeochemical Responses To Predicted Climate Change Scenarios, Angela R. Shaffer
College of Graduate Studies: Theses & Dissertations
Wetlands are one of the world's largest known carbon sinks while comprising only a small amount of the Earth's surface. However, the amount of carbon sequestered by wetlands is shrinking as droughts and human disturbance increases. Carbon in wetlands is stored through the contrast of decomposition and sedimentation of organic matter and absorption of CO2 from the atmosphere by soil microbes. Understanding how changing hydrological regimes and increased wildfires will affect wetland soil and microbial processes is important in the face of predicted climate change for future wetland conservation practices. Specifically, I seek to understand the response of southeastern …
Novel Hybrid Analogs Of Estrone Origin Exhibits Cytotoxic Effects Against Egfr-Dependent Cancers,
2019
South Dakota State University
Novel Hybrid Analogs Of Estrone Origin Exhibits Cytotoxic Effects Against Egfr-Dependent Cancers, Felix Acheampong
Electronic Theses and Dissertations
Cancer is second only to cardiovascular illnesses as the deadliest human disease globally. Currently, non-small cell lung cancer (NSCLC) and triple negative breast carcinoma (TNBC) are the most frequent types of cancer and have the highest mortalities. Epidermal growth factor receptor (EGFR), a central regulator of tumor progression, is frequently overexpressed in both cancers and is a key clinical target for therapeutic intervention. Natural products and their synthetic analogs have been utilized as EGFR tyrosine kinase inhibitors (TKIs) with potent antitumor effects. However, acquired resistance limits the long-term efficacy of these drugs. Estrone has been used as a scaffold in …
Disease Resistance In Wheat And Its Relatives,
2019
South Dakota State University
Disease Resistance In Wheat And Its Relatives, Ethan James Andersen
Electronic Theses and Dissertations
Plants have evolved a complex defense system against pests and pathogens utilizing many types of receptors, signaling factors, and defense compounds to detect pathogen presence and respond effectively. Since many pathogens have evolved immunesuppressing effectors used to reduce plant resistance, plants have evolved a family of receptors that detect pathogenic effectors as a result of an evolutionary arms race. These receptors contain Nucleotide-Binding Site and Leucine-Rich Repeat domains and are called NBS-LRR or NLR proteins. Many grasses possess huge genomes with hundreds of NLR-encoding genes, often found in clusters at the extra-pericentromeric regions of chromosomes, where unequal crossing over causes …
Ligand Binding And Signaling Of Hare/Stabilin-2,
2019
University of Nebraska - Lincoln
Ligand Binding And Signaling Of Hare/Stabilin-2, Edward N. Harris, Fatima Cabral
Department of Biochemistry: Faculty Publications
The Stabilin receptors are a two-member family in the type H class of scavenger receptors. These dynamic receptors bind and internalize multiple ligands from the cell surface for the purpose of clearing extracellular material including some synthetic drugs and for sensing the external environment of the cell. Stabilin-1 was the first receptor to be cloned, though the biological activity of Hyaluronic Acid Receptor for Endocytosis (HARE)/Stabilin-2 was observed about 10 years prior to the cloning of Stabilin-1. Stabilin-1 has a more diverse expression profile among the tissues than HARE/Stabilin-2. This review will focus on HARE/Stabilin-2 and its interactions with hyaluronan, …
Genome‐Wide Association And Genomic Prediction For Biomass
Yield In A Genetically Diverse Miscanthus Sinensis Germplasm
Panel Phenotyped At Five Locations In Asia And North America,
2019
University of Illinois at Urbana-Champaign
Genome‐Wide Association And Genomic Prediction For Biomass Yield In A Genetically Diverse Miscanthus Sinensis Germplasm Panel Phenotyped At Five Locations In Asia And North America, Lindsay V. Clark, Maria S. Dwiyanti, Kossonou G. Anzoua, Joe E. Brummer, Bimal Kumar Ghimire, Katarzyna Glowacka, Megan Hall, Kweon Heo, Xiaoli Jin, Alexander E. Lipka, Junhua Peng, Toshihiko Yamada, Ji Hye Yoo, Chang Yeon Yu, Hua Zhao, Stephen P. Long, Erik J. Sacks
Department of Biochemistry: Faculty Publications
To improve the efficiency of breeding of Miscanthus for biomass yield, there is a need to develop genomics‐assisted selection for this long‐lived perennial crop by relating genotype to phenotype and breeding value across a broad range of environments. We present the first genome‐wide association (GWA) and genomic prediction study of Miscanthus that utilizes multilocation phenotypic data. A panel of 568 Miscanthus sinensis accessions was genotyped with 46,177 single nucleotide polymorphisms (SNPs) and evaluated at one subtropical and five temperate locations over 3 years for biomass yield and 14 yield‐component traits. GWA and genomic prediction were performed separately for different years …
Downregulation Of A Cyp74 Rubber
Particle Protein Increases Natural
Rubber Production In Parthenium
Argentatum,
2019
USDA, Agricultural Research Service
Downregulation Of A Cyp74 Rubber Particle Protein Increases Natural Rubber Production In Parthenium Argentatum, Dante F. Placido, Niu Dong, Chen Dong, Von Mark V. Cruz, David A. Dierig, Rebecca E. Cahoon, Byung-Guk Kang, Trinh Huynh, Maureen Whalen, Grisel Ponciano, Colleen Mcmahan
Department of Biochemistry: Faculty Publications
We report functional genomics studies of a CYP74 rubber particle protein from Parthenium argentatum, commonly called guayule. Previously identified as an allene oxide synthase (AOS), this CYP74 constitutes the most abundant protein found in guayule rubber particles. Transgenic guayule lines with AOS gene expression down-regulated by RNAi (AOSi) exhibited strong phenotypes that included agricultural traits conducive to enhancing rubber yield. AOSi lines had higher leaf and stem biomass, thicker stembark tissues, increased stem branching and improved net photosynthetic rate. Importantly, the rubber content was significantly increased in AOSi lines compared to the wild-type (WT), vector control and …
Effects And Mechanisms Of Anacardium Occidentale And Glochidion Zeylanicum Leaf Extracts On Neuroprotective, Neuritogenesis, Oxidative Stress Resistance And Anti-Aging Properties.,
2019
Faculty of Allied Health Sciences
Effects And Mechanisms Of Anacardium Occidentale And Glochidion Zeylanicum Leaf Extracts On Neuroprotective, Neuritogenesis, Oxidative Stress Resistance And Anti-Aging Properties., Chatrawee Duangjan
Chulalongkorn University Theses and Dissertations (Chula ETD)
Aging is the primary risk factor for most neurodegenerative diseases and can negatively affect the quality of life. Neurodegenerative diseases are linked to neuronal cell death and neurite outgrowth impairment that are often caused by oxidative stress. As people want to live longer and healthier, healthy nutrition has been increasingly received much attention in recent years. Several studies reported a positive correlation between antioxidants in foods and longevity. Natural products from food supplements and medicinal plants with antioxidant properties could be promising candidates for fighting against various aging-related diseases and promoting longevity. Leaf extracts from A. occidentale (AO) and G. …
Functional Characterization Of Glutamate Carboxypeptidase Ii In Caenorhabditis Elegans,
2019
Eastern Illinois University
Functional Characterization Of Glutamate Carboxypeptidase Ii In Caenorhabditis Elegans, Hashni Epa Vidana Gamage
Masters Theses
Glutamate carboxypeptidase II (GCPII) is a transmembrane zinc metalloprotease expressed in a number of organisms: from yeast to worm to humans. In humans, GCPII has been observed as a multifunctional protein and expressed in prostate, intestine, kidney, brain, tumor-associated neovasculature and other tissues as five paralogs. In the human small intestine, hGCPII is proposed to facilitate the folate absorption by cleaving terminal glutamate residues in dietary folates. Folates act as a cofactor in one-carbon metabolic pathways such as nucleotide synthesis, amino acid synthesis, DNA repair, and consequently involved in cell division and growth. The hGCPII homolog is found in the …
Regorafenib Enhances Lethality Of Sildenafil And Curcumin In Colorectal Cancer Cells,
2019
Virginia Commonwealth University
Regorafenib Enhances Lethality Of Sildenafil And Curcumin In Colorectal Cancer Cells, Kervin Benjamin Owusu
Theses and Dissertations
In the United States, more than 130,000 people will be diagnosed with colorectal cancer (CRC) each year and an estimated 50,000 people will die from the disease. Standard of care (SOC) therapies for CRC combine multiple cytotoxic chemotherapeutic drugs. These combinations have varying degrees of effectiveness and can often result in significant patient morbidity. For second recurrence patients, the multi-kinase inhibitor, regorafenib, is an approved agent, but is often poorly tolerated at current doses. In the current study, we propose to develop therapeutic regime of combining agents with modest toxicity profiles: curcumin and sildenafil with regorafenib. Using clinically achievable enterohepatic …
Using Lipidomics To Characterize The Inflammatory Mechanisms In Sepsis And Pre-Eclampsia,
2019
Virginia Commonwealth University
Using Lipidomics To Characterize The Inflammatory Mechanisms In Sepsis And Pre-Eclampsia, Daniel Stephenson
Theses and Dissertations
Lipidomics, a rapidly developing field of study, focuses on the classification and quantitation of lipid species. Lipidomics has emerged in the forefront of scientific research due to the key roles that lipids play in metabolism, cancer, and disease. Using mass spectrometry as a tool for analysis, understanding the role eicosanoids and sphingolipids play has advanced rapidly. Being able to observe these small molecules in vivo has led to better understanding of several lipid-driven mechanisms and identification of eicosanoid and sphingolipid biomarkers in neurodegenerative disease, cancer, sepsis, wound healing, and pre-eclampsia. In the studies herein, we developed targeted mass spectrometric methods …
Biometal-Induced Structural Consequences Of Α-Synuclein – The Parkinson’S Disease Protein,
2019
Virginia Commonwealth University
Biometal-Induced Structural Consequences Of Α-Synuclein – The Parkinson’S Disease Protein, Dinendra L. Abeyawardhane
Theses and Dissertations
The pre-synaptic protein α-Synuclein (αS) is often linked to the pathology of Parkinson’s disease (PD), an age-related neurodegenerative disorder. Lewy bodies, the cytopathological hallmarks of PD, are found to be rich in aggregates of misfolded αS protein. Metal dyshomeostasis has also been linked to PD due to the accumulation of iron in the substantia nigra pars compacta, and diminished copper levels reported in this same region. Metal dyshomeostasis in the brain coupled with oxidative stress can enhance the aggregation of αS. Recently, it was confirmed that mammalian αS is universally acetylated at the N-terminus, a common post-translational modification in …
Analysis Of The Molecular Mechanisms Governing Fcγ Receptor Activation On The Surfaces Of Macrophages By Advanced Optical Microscopy,
2019
South Dakota State University
Analysis Of The Molecular Mechanisms Governing Fcγ Receptor Activation On The Surfaces Of Macrophages By Advanced Optical Microscopy, Elizabeth Michelle Bailey
Electronic Theses and Dissertations
Therapeutic antibodies are achieving new levels of therapeutic success in treating cancers and immunological disorders by antibody engagement of Fc receptor-directed immune responses. Conversely, inhibiting autoantibody induced Fc receptor activation is an attractive approach to treat autoimmune diseases. Immunoglobulin G (IgG) antibodies are often the principal subclass used in therapeutic antibodies and associated with autoimmune pathologies because of their long circulation and potent effector functions, including activation of the Fcγ Receptor (FcγR). Thus, a thorough understanding of the FcγR activation is required to improve the efficacy of immunotherapies and to mitigate autoimmunities. It is well established that FcγR clustering is …
