Folding Of Gα Subunits: Implications For Disease States,
2018
Loyola University Chicago
Folding Of Gα Subunits: Implications For Disease States, Matthew Najor, Brian D. Leverson, Jesse L. Goossens, Saad Kothawala, Kenneth W. Olsen, Duarte Mota De Freitas
Chemistry: Faculty Publications and Other Works
G-proteins play a central role in signal transduction by fluctuating between “on” and “off” phases that are determined by a conformational change. cAMP is a secondary messenger whose formation is inhibited or stimulated by activated Giα1 or Gsα subunit. We used tryptophan fluorescence, UV/vis spectrophotometry, and circular dichroism to probe distinct structural features within active and inactive conformations from wild-type and tryptophan mutants of Giα1 and Gsα. For all proteins studied, we found that the active conformations were more stable than the inactive conformations, and upon refolding from higher temperatures, activated wild-type subunits recovered significantly more native structure. We also …
Allosteric Regulation Of Pyruvate Carboxylase,
2018
Marquette University
Allosteric Regulation Of Pyruvate Carboxylase, Yumeng Liu
Dissertations (1934 -)
Pyruvate carboxylase (PC; E.C.6.4.1.1) is a multifunctional, biotin-dependent enzyme that catalyzes the MgATP-dependent carboxylation of pyruvate to oxaloacetate. The overall reaction is accomplished by the coupling of two half reactions occurring at two spatially distinct catalytic domains by the translocation of a carrier domain, resulting in a net transfer of CO2 from bicarbonate to pyruvate. PC activity is regulated by multiple allosteric effectors with acetyl CoA serving as an activator in most species and L-aspartate serving as an inhibitor for microbial PC. The kinetic characterization of PC from different species have revealed that PC homologs are subject to divergent degrees …
Regulation Of Beta-Catenin By The Ctlh Complex,
2018
The University of Western Ontario
Regulation Of Beta-Catenin By The Ctlh Complex, Christopher Chiasson
Electronic Thesis and Dissertation Repository
RanBPM is a highly conserved protein that has been shown to impact numerous cellular processes including migration, proliferation, and apoptosis. RanBPM exists in a multi-protein complex called the CTLH complex, which functions as an E3 ubiquitin ligase. A putative member of the CTLH complex, WDR26, has been implicated in the Wnt pathway through regulating β-catenin protein levels. This study investigated whether β-catenin regulation is performed by the CTLH complex. WDR26 was confirmed as part of the CTLH complex, and this complex is interacting with Axin1. CTLH members RanBPM and RMND5A both regulate beta-catenin levels in a proteasome dependent manner. Additionally, …
Phenotypic Screening Identifies Brefeldin A/Ascotoxin
As An Inducer Of Lipid Storage In The Algae
Chlamydomonas Reinhardtii,
2018
University of Nebraska-Lincoln
Phenotypic Screening Identifies Brefeldin A/Ascotoxin As An Inducer Of Lipid Storage In The Algae Chlamydomonas Reinhardtii, Nishikant Wase, Boqiang Tu, Paul N. Black, Concetta C. Dirusso
Nishikant Wase
The use of microalgae as a biofuel feedstock is highly desired, but current methods to induce lipid accumulation cause severe stress responses that limit biomass and, thus oil yield. To address these issues, a high throughput screening (HTS) method was devised to identify chemical inducers of growth and lipid accumulation. Optimization was performed to determine the most effective cell density, DMSO and Nile Red (NR) concentrations to monitor growth and lipid accumulation. The method was tested using 1717 compounds from National Cancer Institute (NCI) Diversity Set III and Natural Products Set II in Chlamydomonas reinhardtii. Cells were inoculated at …
The Distinctive Regulatory Mechanisms Of Bacterial Acetyl-Coa Carboxylase,
2018
Louisiana State University and Agricultural and Mechanical College
The Distinctive Regulatory Mechanisms Of Bacterial Acetyl-Coa Carboxylase, Alexandra Leigh Evans
LSU Doctoral Dissertations
Metabolic Regulation is a complex system used to control cellular metabolism in response to conditions in the cell’s environment. For most enzymes, the cell can rely upon a minimal amount of regulation; however, critical enzymes, such as acetyl-CoA carboxylase, must be regulated at multiple levels. Acetyl-CoA carboxylase catalyzes the first committed step in fatty acid synthesis. In bacteria, acetyl-CoA carboxylase forms a complex of three subunits–biotin carboxylase, biotin carboxyl carrier protein, and carboxyltransferase–which catalyze the carboxylation of acetyl-CoA to form malonyl-CoA via two half-reactions. In the first half-reaction, biotin covalently linked to biotin carboxyl carrier protein is carboxylated by biotin …
Optimizing Spacer Length For Positioning Functional Groups In Bio-Waste,
2018
CUNY Borough of Manhattan Community College
Optimizing Spacer Length For Positioning Functional Groups In Bio-Waste, Revathi Iyengar, Maria Faure-Betancourt, Saleh Talukdar, Jinting Ye, Abel E. Navarro
Publications and Research
The goal of this study was to determine the optimal chain length needed for tethering functional groups on bio-wastes. The purpose of modifying the surface of bio-waste is to improve their affinity for phenols. To this end, four different aminated green tea leaves, with the amine group located at the end of 6, 8, 10, and 12 carbons were synthesized. Green approaches to functionalization lead to fewer reactive sites. Optimizing spacer length is one way to ameliorate this. The aminated tea leaves were prepared by a tosylation reaction followed by displacement with a diamine used in excess. The tea leaves …
Men’S Health In Industries: Plastic Plant Pollution And Prevalence Of Pre-Diabetes And Type 2 Diabetes Mellitus,
2018
King Saud University, Riyadh, Saudi Arabia
Men’S Health In Industries: Plastic Plant Pollution And Prevalence Of Pre-Diabetes And Type 2 Diabetes Mellitus, Sultan Ayoub Meo, Faris Jamal Almutairi, Majed Mohammed Alasbali, Turki Badr Alqahtani, Saad Saeed Almutairi, Rakan Abdulaziz Albuhayjan, Fawziah Al Rouq, Naseer Ahmed
Department of Biological & Biomedical Sciences
Plastic production is prominently increasing and its pollution is an emerging environmental global health concern. This study aimed to investigate the occurrence of pre-diabetes and type 2 diabetes mellitus (T2DM) among nonsmoking plastic industry workers. Three hundred and forty volunteers male plastic industry workers were interviewed after medical history and examination; finally, 278 nonsmoking plastic industry workers were selected. The mean age for the participants was 38.03 ± 10.86 years and body mass index was 25.52 ± 3.15 (kg/m)2. The plastic industry workers had been exposed to plastic plant pollution for 8 hr daily, 6 days in a …
Towards An Atomic Level Model Of The Structure And Calmodulin Mediated Activation Of Eef-2k,
2018
The Graduate Center, City University of New York
Towards An Atomic Level Model Of The Structure And Calmodulin Mediated Activation Of Eef-2k, Nathan E. Will
Dissertations, Theses, and Capstone Projects
Eukaryotic elongation factor 2 kinase (eEF-2K), the only calmodulin (CaM) dependent member of the a-kinase, phosphorylates eukaryotic elongation factor 2 (eEF-2) on a specific residue (Thr-56), decreasing its affinity for the ribosome and reducing the rate of peptide chain elongation during protein translation. In contrast to the “release-of-inhibition’ mechanism operative in most CaM-dependent proteins kinases, the activation of eEF-2K is proposed to occur through a two-step process subsequent to the engagement of CaM and involves (1) auto-phosphorylation on T348 and (2) engagement of an allosteric site by phospho-T348 leading to a state with the highest activity towards the substrate eEF-2. …
Small Noncoding Rna Profiles Along Alternative Developmental Trajectories In An Annual Killifish,
2018
Portland State University
Small Noncoding Rna Profiles Along Alternative Developmental Trajectories In An Annual Killifish, Amie L. Romney, Jason E. Podrabsky
Biology Faculty Publications and Presentations
Embryonic development of Austrofundulus limnaeus can occur along two phenotypic trajectories that are physiologically and biochemically distinct. Phenotype appears to be influenced by maternal provisioning based on the observation that young females produce predominately non-diapausing embryos and older females produce mostly diapausing embryos. Embryonic incubation temperature can override this pattern and alter trajectory. We hypothesized that temperature-induced phenotypic plasticity may be regulated by post-transcriptional modification via noncoding RNAs. As a first step to exploring this possibility, RNA-seq was used to generate transcriptomic profiles of small noncoding RNAs in embryos developing along the two alternative trajectories. We find distinct profiles of …
Induction Of Oil Accumulation By Heat Stress Is Metabolically Distinct From N Stress In The Green Microalgae Coccomyxa Subellipsoidea C169,
2018
University of Nebraska-Lincoln
Induction Of Oil Accumulation By Heat Stress Is Metabolically Distinct From N Stress In The Green Microalgae Coccomyxa Subellipsoidea C169, James W. Allen, Rahul Tevatia, Yaşar Demirel, Concetta C. Dirusso, Paul N. Black
Department of Biochemistry: Faculty Publications
Algae are often promoted as feedstock organisms to produce a sustainable petroleum fossil fuel alternative. However, to induce lipid accumulation most often requires a severe stress that is difficult to induce in large batch cultures. The objective of this study is to analyze and mathematically model heat stress on growth, chlorophyll content, triacylglyceride, and starch synthesis in algae. We initially screened 30 algal species for the most pronounced induction of lipid droplets from heat stress using confocal microscopy and mass spectroscopy techniques. One species, Coccomyxa subellipsoidea C169, was selected and subjected to further biochemical analyses using a jacketed bioreactor amended …
Phospholipase D-Dependent Mtorc1 Activation By Glutamine,
2018
The Graduate Center, City University of New York
Phospholipase D-Dependent Mtorc1 Activation By Glutamine, Elyssa Bernfeld
Dissertations, Theses, and Capstone Projects
Glutamine, the conditionally essential amino acid and most abundant amino acid in human sera, is a key nutrient required for sustaining cell proliferation. Glutamine is essential for nucleotide, protein, and lipid synthesis, all of which are essential for cell proliferation. The mammalian target of rapamycin complex 1 (mTORC1) is a highly conserved protein complex that acts as a sensor of nutrients, relaying signals for the shift from catabolic to anabolic metabolism. While glutamine plays an important role in activating mTORC1, the mechanism is not completely clear. Here we describe a Rag-independent mechanism of mTORC1 activation by glutamine that is dependent …
A Novel Exo-Proteomic Approach To The Study Of Traumatic Brain Injury,
2018
Loma Linda University
A Novel Exo-Proteomic Approach To The Study Of Traumatic Brain Injury, Ron B. Moyron
Loma Linda University Electronic Theses, Dissertations & Projects
Concussions and Traumatic Brain Injuries (TBI) are significant health concerns and affect a wide cross section of society. Current diagnostic criteria and modalities, such as brain imaging and subjective measures of consciousness such as the Glasgow Coma Scale (GCS) score, are insufficient to properly diagnose the full spectrum of head injuries. Assessment of injury severity and outcome are further complicated by the vast array of symptoms, many of which mimic those displayed by other disorders. It is important to possess a better diagnostic tool for head injury triage and outcome prediction. One current line of inquiry seeks to discover a …
Supercharged Models Of Intrinsically Disordered Proteins And Their Utility In Sensing,
2018
The Graduate Center, City University of New York
Supercharged Models Of Intrinsically Disordered Proteins And Their Utility In Sensing, Peter J. Schnatz
Dissertations, Theses, and Capstone Projects
In this thesis I show that greatly increasing the magnitude of a protein’s net charge using surface supercharging transforms that protein into a ligand-gated or counterion-gated conformational molecular switch. To demonstrate this I first modified the designed helical bundle hemoprotein H4 using simple molecular modeling, creating a highly charged protein which both unfolds reversibly at low ionic strength and undergoes the ligand-induced folding transition commonly observed in signal transduction by intrinsically disordered proteins in biology. Due to the high surface charge density, ligand binding to this protein is allosterically activated by low concentrations of divalent cations and the polyamine spermine. …
Renal Risk Variants Of Apolipoprotein L-1 Form Channels At The Plasma Membrane That Lead To A Cytotoxic Influx Of Calcium,
2018
The Graduate Center, City University of New York
Renal Risk Variants Of Apolipoprotein L-1 Form Channels At The Plasma Membrane That Lead To A Cytotoxic Influx Of Calcium, Joseph A. Giovinazzo
Dissertations, Theses, and Capstone Projects
Apolipoprotein L-1 (APOL1) is a secreted protein that provides protection against several protozoan parasites due to its channel forming properties. Recently evolved variants, G1 and G2, increase kidney disease risk when present in two copies. In mammalian cells, overexpression of G1 and G2, but not wild-type G0, leads to swelling and eventual lysis. However, the mechanism of cell death remains elusive with multiple pathways being invoked, such as autophagic cell death mediated by a BH3 domain in APOL1, which we evaluated in this study. We hypothesized that the common trigger for these pathways is the APOL1 cation channel, which is …
Identification Of Biologically Essential Nodes Via Determinative Power In Logical Models Of Cellular Processes,
2018
University of Nebraska at Omaha
Identification Of Biologically Essential Nodes Via Determinative Power In Logical Models Of Cellular Processes, Trevor Pentzien, Bhanwar L. Puniya, Tomas Helikar, Mihaela T. Matache
Department of Biochemistry: Faculty Publications
A variety of biological networks can bemodeled as logical or Boolean networks. However, a simplification of the reality to binary states of the nodes does not ease the difficulty of analyzing the dynamics of large, complex networks, such as signal transduction networks, due to the exponential dependence of the state space on the number of nodes. This paper considers a recently introduced method for finding a fairly small subnetwork, representing a collection of nodes that determine the states of most other nodes with a reasonable level of entropy. The subnetwork contains the most determinative nodes that yield the highest information …
A Hybrid Lagrangian–Eulerian Particle Model For Ecosystem Simulation,
2018
Michigan Technological University
A Hybrid Lagrangian–Eulerian Particle Model For Ecosystem Simulation, Pengfei Xue, David J. Schwab, Xing Zhou, Chenfu Huang, Ryan Kibler, Xinyu Ye
Michigan Tech Publications
Current numerical methods for simulating biophysical processes in aquatic environments are typically constructed in a grid-based Eulerian framework or as an individual-based model in a particle-based Lagrangian framework. Often, the biogeochemical processes and physical (hydrodynamic) processes occur at different time and space scales, and changes in biological processes do not affect the hydrodynamic conditions. Therefore, it is possible to develop an alternative strategy to grid-based approaches for linking hydrodynamic and biogeochemical models that can significantly improve computational efficiency for this type of linked biophysical model. In this work, we utilize a new technique that links hydrodynamic effects and biological processes …
Direct Quantification Of Deubiquitinating Enzyme Activity In Single Intact Cells,
2018
Louisiana State University and Agricultural and Mechanical College
Direct Quantification Of Deubiquitinating Enzyme Activity In Single Intact Cells, Nora Safabakhsh
LSU Doctoral Dissertations
Challenges in drug efficacy occur during the treatment of most types of cancer due to the heterogeneity of the tumor microenvironment. This has led to the development of personalized medicine. Due to the clinical success of the proteasome inhibitors Bortezomib and Carfilzomib in treatment of multiple myeloma, interest has shifted towards molecularly-targeted chemotherapeutics for ubiquitin-proteasome system (UPS). Deubiquitinating enzymes (DUBs) are an essential part of this pathway which have been found to promote Bortezomib resistance in multiple myeloma patients. Unfortunately, there is a lack of specific, high throughput biochemical assays to characterize DUB activity in patient samples before and after …
Building On Nature: Spectroscopic Studies Of Photosynthesis-Inspired Pigments, Fused Light Harvesting Proteins, And Bacterial Reaction Center Mutants,
2018
Washington University in St. Louis
Building On Nature: Spectroscopic Studies Of Photosynthesis-Inspired Pigments, Fused Light Harvesting Proteins, And Bacterial Reaction Center Mutants, Kaitlyn Faries
Arts & Sciences Electronic Theses and Dissertations
Photosynthesis is the dominant form of solar energy conversion on the planet, making it critical to understand the fundamentals of the process in order to effectively mimic and improve upon it for human energy needs. The initial stages of photosynthesis include light harvesting and chemical conversion of that harvested energy via electron transport, with both of these stages relying on pigments (or chromophores) such as chlorophyll and specific protein architectures for the processes. In this work, the fundamental underpinnings of photosynthetic light harvesting and electron transport are explored via spectroscopy of various photosynthetic systems with altered natural pigments and proteins. …
The Mechanism Of Hyper Daptomycin Resistance In Corynebacterium Striatum And Daptomycinճ Mechanism Of Action,
2018
Washington University in St. Louis
The Mechanism Of Hyper Daptomycin Resistance In Corynebacterium Striatum And Daptomycinճ Mechanism Of Action, Nicholas Kevork Goldner
Arts & Sciences Electronic Theses and Dissertations
Daptomycin, a last line-of-defense antibiotic for treating Gram-positive infections, is experiencing clinical failure against important infectious agents, including Corynebacterium striatum. The recent transition of daptomycin to generic antibiotic status is projected to dramatically increase availability, use, and clinical failure. Despite daptomycinճ more than 30-year history as an important antibiotic, four major questions were left unanswered. 1) How do bacteria become hyper-resistant to daptomycin? 2) What is the in vivo membrane target of daptomycin? 3) How does daptomycin interact with the membrane? 4) What is daptomycinճ mechanism of killing? These four questions have plagued the daptomycin field, and even now conflicting …
Plant Metabolic Pathways And Regulatory Networks For Aromatic Amino Acids And Hormones,
2018
Washington University in St. Louis
Plant Metabolic Pathways And Regulatory Networks For Aromatic Amino Acids And Hormones, Cynthia Holland
Arts & Sciences Electronic Theses and Dissertations
Unlike humans and other metazoans, organisms such as fungi, bacteria, and plants have retained the enzymatic machinery necessary to synthesize their aromatic amino acids de novo. Chorismate, the final product of the shikimate pathway, is the precursor to the three aromatic amino acidsѠtryptophan, tyrosine, and phenylalanineѠand is upstream of a number of plant growth hormones, including auxins and benzoates. Phenylalanine and tyrosine both stem from the precursor prephenate, which is formed from chorismate by chorismate mutase, and use dehydrogenases, aminotransferases, and dehydratases in their biosynthetic pathways. Although aromatic amino acid biosynthesis is important for protein synthesis, secondary metabolism, and human …
