Biochemistry Commons^™

Regulation Of Liver Mitochondrial Metabolism During Hibernation By Post-Translational Modification, Katherine E. Mathers

Electronic Thesis and Dissertation Repository

Hibernation, characterized by a seasonal reduction in metabolism and body temperature, allows animals to conserve energy when environmental conditions (e.g. temperature, food availability) are unfavourable. During hibernation, small mammals such as the 13-lined ground squirrel (Ictidomys tridecemlineatus) cycle between two distinct metabolic states: torpor, where metabolic rate is suppressed by >95% and body temperature falls to ~5 °C, and interbout euthermia (IBE), where metabolic rate and body temperature rapidly increase and are maintained at euthermic levels several hours. Suppression of metabolism during entrance into torpor is paralleled by rapid suppression of liver mitochondrial metabolism. In my thesis, I …

Design And Synthesis Of Analogs Of Myo-Inositol, Serine, And Cysteine To Enable Chemical Biology Studies, Tanei J. Ricks

Doctoral Dissertations

Phosphorylated myo-inositol compounds including inositol phosphates (InsPs) as well as the phosphatidylinositol polyphosphate lipids (PIP_ns) are critical biomolecules that regulate many of the most important biological processes and pathways. They are aberrant in many disease states due to their regulatory function. The same is true of the phospholipid phosphatidylserine (PS) which can serve as a marker to begin apoptosis. However, the full scope of activities of these structures is not clear, particularly since techniques that enable global detection and analysis of the production of these compounds spatially and temporally are lacking. With all of these obstacles in …

Insights Into The Therapeutic Potential Of Salt Inducible Kinase 1: A Novel Mechanism Of Metabolic Control, Randi Fitzgibbon

Dissertations & Theses (Open Access)

Salt inducible kinase 1 (SIK1) has been considered a stress-inducible kinase since it was first cloned in 1999. Continued efforts since this time have been dedicated to characterizing the structure and function of SIK1. Such research has laid the ground work for our understanding of SIK1 action and regulation in tissue and stimuli dependent manners. The fundamental findings of this dissertation continue in this tradition and include investigations of SIK1 regulatory mechanisms in skeletal muscle cells, the cellular and physiological effects of SIK1 loss of function in vitro and in vivo, and intracellular metabolic and mitochondrial regulation by this …

A Potential Solution To A Poopy Problem: Bile Salt Analogs As Prophylactics Against Clostridium Difficile Infection, Jacqueline Renee Phan

UNLV Theses, Dissertations, Professional Papers, and Capstones

Clostridium difficile infection (CDI) is a major cause of antibiotic-associated diarrhea. In 2011, over 500,000 patients were diagnosed with CDI in the United States and over 29,000 people died of CDI-related complications. With an average of $35,000 to treat a single case of inpatient CDI, cost burden to the healthcare system can reach up to $3.2 billion annually. As both hospital- and community-acquired CDI incidences rise due to the emergence of hypervirulent strains and CDI reoccurrences of up to 25%, standard treatments are rendered less effective and new methods of prevention are critical.

CDI is caused by bacteria called Clostridium …

Disorder Levels Of C-Myb Transactivation Domain Regulate Its Binding Affinity To The Kix Domain Of Creb Binding Protein, Anusha Poosapati

USF Tampa Graduate Theses and Dissertations

Intrinsically disordered proteins (IDPs) do not form stable tertiary structures like their ordered partners. They exist as heterogeneous ensembles that fluctuate over a time scale. Intrinsically disordered regions and proteins are found across different phyla and exert crucial biological functions. They exhibit transient secondary structures in their free state and become folded upon binding to their protein partners via a mechanism called coupled folding and binding. Some IDPs form alpha helices when bound to their protein partners. We observed a set of cancer associated IDPs where the helical binding segments of IDPs are flanked by prolines on both the sides. …

Investigating The Toxicity And Accumulation Of 2,4-Dichlorophenoxyacetic Acid (2,4-D) And Glyphosate In Eisenia Fetida, Caitlin Lazurick, Nicole Lidzbarski, Rachel Owings, Jeff Brotherton, Edna Steele

Journal of the South Carolina Academy of Science

Glyphosate, the main ingredient in Roundup^®, is the most widely used herbicide in the world. It is also used in combination with another effective herbicide, 2,4-D, in the formulation called Enlist Duo^®. The EPA approved the use of Enlist Duo^® on certain crops including those genetically modified to be resistant to both herbicides. The predicted significant increase in the use of these herbicides raised concerns from the general public because both compounds have been classified as possibly or probably carcinogenic. Since herbicides are applied directly to vegetation, the safety of organisms that come in contact …

Photosensing And Thermosensing By Phytochrome B Require Both Proximal And Distal Allosteric Features Within The Dimeric Photoreceptor, E Sethe Burgie, Adam N. Bussell, Shu-Hui Lye, Tong Wang, Weiming Hu, Katrice E. Mcloughlin, Erin L. Weber, Huilin Li, Richard D. Vierstra

Biology Faculty Publications & Presentations

Phytochromes (Phys) encompass a diverse collection of bilin-containing photoreceptors that help plants and microorganisms perceive light through photointerconversion between red light (Pr) and far-red light (Pfr)-absorbing states. In addition, Pfr reverts thermally back to Pr via a highly enthalpic process that enables temperature sensation in plants and possibly other organisms. Through domain analysis of the Arabidopsis PhyB isoform assembled recombinantly, coupled with measurements of solution size, photoconversion, and thermal reversion, we identified both proximal and distal features that influence all three metrics. Included are the downstream C-terminal histidine kinase-related domain known to promote dimerization and a conserved patch just upstream …

Differential Uptake Of Gold Nanoparticles By 2 Species Of Tadpole, The Wood Frog (Lithobates Sylvaticus) And The Bullfrog (Lithobates Catesbeianus), Lucas B. Thompson, Gerardo L.F. Carfagno, Kurt Andresen, Andrea J. Sitton, Taylor B. Bury, Laura L. Lee, Kevin T. Lerner, Peter P. Fong

Biology Faculty Publications

Engineered nanoparticles are aquatic contaminants of emerging concern that exert ecotoxicological effects on a wide variety of organisms. We exposed cetyltrimethylammonium bromide–capped spherical gold nanoparticles to wood frog and bullfrog tadpoles with conspecifics and in combination with the other species continuously for 21 d, then measured uptake and localization of gold. Wood frog tadpoles alone and in combination with bullfrog tadpoles took up significantly more gold than bullfrogs. Bullfrog tadpoles in combination with wood frogs took up significantly more gold than controls. The rank order of weight-normalized gold uptake was wood frogs in combination > wood frogs alone > bullfrogs in combination …

Mechanisms And Regulation Of Resection In Dna Damage Response, Sharad C. Paudyal

Arts & Sciences Electronic Theses and Dissertations

Deoxyribonucleic acid (DNA) encodes genetic information essential for cell survival and function. However, it is constantly under assault from endogenous and exogenous damaging agents that not only threaten our own survival but also affect the faithful transmission of genetic information to our offspring. Double-strand breaks (DSBs) are one of the most hazardous forms of DNA damage, which if unrepaired or improperly repaired could lead to plethora of systemic human diseases including cancer. To deal with this problem, cells have evolved with a mechanism called DNA damage response (DDR) to detect, signal, and repair the breaks by inducing multiple cellular events. …

Performing A Genetic Screen To Identify Factors That Promote Lncrna-Dependent Gene Repression, Chrishan Fernando, Cecilia Yiu, Sara Cloutier, Siwen Wang, Elizabeth Tran

The Summer Undergraduate Research Fellowship (SURF) Symposium

Long non-coding RNAs (lncRNAs) were once thought not to have useful functions in organisms but rather to be products of aberrant transcription. However, roles are being found for lncRNAs in beneficial processes such as controlling gene expression. In some of these cases, lncRNAs form R-loops in vivo. R-loops are nucleic acid structures consisting of hybridized strands of single-stranded DNA (ssDNA) and single-stranded RNA (ssRNA) as well as the displaced strand of ssDNA. Formation of these R-loops is important for gene regulation by the lncRNAs. However, factors that promote formation of lncRNA R-loops are not known. The gene PHO84 is being …

Cellular And Molecular Targets Of Menthol Actions, Murat Oz, Eslam El Nebrisi, Keun-Hang Susan Yang, Frank Christopher Howarth, Lina T. Al Kury

Mathematics, Physics, and Computer Science Faculty Articles and Research

Menthol belongs to monoterpene class of a structurally diverse group of phytochemicals found in plant-derived essential oils. Menthol is widely used in pharmaceuticals, confectionary, oral hygiene products, pesticides, cosmetics, and as a flavoring agent. In addition, menthol is known to have antioxidant, anti-inflammatory, and analgesic effects. Recently, there has been renewed awareness in comprehending the biological and pharmacological effects of menthol. TRP channels have been demonstrated to mediate the cooling actions ofmenthol. There has been new evidence demonstrating thatmenthol can significantly influence the functional characteristics of a number of different kinds of ligand and voltage-gated ion channels, indicating that at …

Autophagy Inhibition In Pain: Role Of A Microrna, Andrea Stevens

D.U.Quark

Neuropathic pain caused by peripheral nerve injury (PNI) leads to the activation and infiltration of microglial cells and to a neuroinflammatory-induced pain state. miRNAs and autophagy are two main factors and/or mechanisms which have the ability to alter the pain state. In this study, miR-195 was shown to be markedly increased after PNI and associated with the pain phenotype. In addition, inhibition of autophagy in vivo led to p62 accumulation, decreased production of LC3, and inhibition of ATG14.

Hsp70 Conformational Plasticity Allows For Expansive Chaperone Role, Megan Bean

D.U.Quark

The Hsp70 system is an essential component of chaperone activity in many organisms. Hsp70 functions include: protein folding, aggregation prevention, trafficking, and enzyme regulation. Hsp70’s ability to bind such a vast array of substrates suggests wide range of conformational plasticity. By utilizing a single mode optical tweezers technique, Mashaghi1 et al., confirms previous theories Hsp70 binds and stabilizes extended peptide segments but also partially folded and near-native protein.

Spatiotemporal Regulation Of Atg1 Kinase Activation In Selective Autophagy, Ning Sun

D.U.Quark

Autophagy is a potent intracellular degradation system and thus its activation requires exquisite regulation to maintain cellular homeostasis. Atg1, a serine-threonine protein kinase, is essential in both selective and non-selective autophagy. New findings suggest that in selective autophagy, Atg1 is activated at the vacuole by convergence of two independent recruitment pathways to prevent aberrant autophagy induction.

The General Amino Acid Permease Gap1 Is Regulated Differentially By Torc1 Activation And Inhibition, Ray Bowman

D.U.Quark

How does cell signaling in response to extracellular stressors impact the trafficking of membrane proteins? In particular, the TORC1 complex plays a key role in this process and while some details of this system have reported, in a recent Journal of Biological Chemistry publication, Andre’s group has revealed new details of this pathway focusing on the general amino acid permease Gap1 as a model cargo. Andre et al. describe a novel and distinct pathway wherein ubiquitylation and downregulation of Gap1 is regulated not only by amino acid-induced activation of TORC1, but also by numerous sources of TORC1 inhibition and cellular …

Plasmodium Falciparum 26s Proteasome Network: A Mystery Solved, Christina Grogan

D.U.Quark

One ofthe most devastating diseases thatthreatens the world population is malaria. The 26S proteasome complex of the malaria parasite Plasmodium falciparum, which was previously unknown, was characterized by the authors through an affinity purification protocol that isolated functional 26S proteasome complexes. This allowed for the identification of subunit composition and PfUSP14, a proteasomeassociated deubiquitinase. This new understanding presents a potential target to disrupt protein regulation in thequest for effective antimalarial strategies.

Growth Trade-Offs Accompany The Emergence Of Glycolytic Metabolism In Shewanella Oneidensis Mr-1, Lon Chubiz, Christopher Marx

Biology Department Faculty Works

Bacteria increase their metabolic capacity via the acquisition of genetic material or by the mutation of genes already present in the genome. Here, we explore the mechanisms and trade-offs involved when Shewanella oneidensis, a bacterium that typically consumes small organic and amino acids, rapidly evolves to expand its metabolic capacity to catabolize glucose after a short period of adaptation to a glucose-rich environment. Using whole-genome sequencing and genetic approaches, we discovered that deletions in a region including the transcriptional repressor (nagR) that regulates the expression of genes associated with catabolism of N-acetylglucosamine are the common basis for evolved glucose metabolism …

Growth Trade-Offs Accompany The Emergence Of Glycolytic Metabolism In Shewanella Oneidensis Mr-1, Lon M. Chubiz, Christopher J. Marx

Lon Chubiz

Estrogen-Activated Mdm2 Disrupts Mammary Tissue Architecture Through A P53-Independent Pathway, Nandini Kundu, Angelika Brekman, Jun Yeob Kim, Gu Xiano, Chong Gao, Jill Bargonetti

Publications and Research

The Cancer Genome Atlas (TCGA) data indicate that high MDM2 expression correlates with all subtypes of breast cancer. Overexpression of MDM2 drives breast oncogenesis in the presence of wild-type or mutant p53 (mtp53). Importantly, estrogen-receptor positive (ER+) breast cancers overexpress MDM2 and estrogen mediates this expression. We previously demonstrated that this estrogen-MDM2 axis activates the proliferation of breast cancer cell lines T47D (mtp53 L194F) and MCF7 (wild-type p53) in a manner independent of increased degradation of wildtype p53 (ie, p53-independently). Herein we present data supporting the role of the estrogen-MDM2 axis in regulating cell proliferation and mammary tissue architecture of …

Altered Na, K- Atpase Isoform Expression In Artemia Franciscana In Response To Hypersaline Environments, Jessica Drenth

Theses and Dissertations

The Na,K-ATPase (NKA) is an essential membrane pump that helps to establish cell ion gradients, and regulate intracellular salt in many organisms. One such species, Artemia franciscana (brine shrimp), extreme halophiles which live in hypersaline environments, expresses 2 distinct α-catalytic subunits of the NKA. One of these subunits, α2-(KK), has two key lysine substitutions located within the cation binding sites. Prior work has demonstrated this specific subunit may be directly involved in brine shrimp adaptation to their extreme environments. However, the precise molecular and physiological effects of α2-(KK) have not been entirely elucidated. I determined through immunohistochemistry that my initial …

Epigenetic Regulation Of Salicylic Acid-Mediated Plant Defense, Phillip Key

Senior Theses

Plant pathogens remain a significant threat to the stability of modern agricultural systems, and the investigation of mechanisms to improve the security of food resources has led to the partial characterization of plant immune response. With this progress, there is a newfound ability to analyze the relative pathogen resistance capability of specifically modified organisms, and in doing so, it is possible to identify individual alterations that might play a role in creating a more robust immune response. In this study, ten Arabidopsis thaliana mutants were infiltrated with Pseudomonas syringae pv. morsprunorum alongside positive and negative control Col-0 Wild-Type and npr1-2. …

A Study On The Interactions Of Trehalose With Model Folate Compounds, Carolyn R Ware

Chancellor’s Honors Program Projects

No abstract provided.

Inquiry Into Perilipin-5a Expression In Triacylglycerol Rich Vs Normal Fed Mouse Tissue, Kobi Agyepong

Undergraduate Honors Thesis Projects

The steep rise in both childhood and adult obesity over the past three decades has moved to the forefront of public consciousness in recent years. This development has generated a marked increase in general health awareness and lifestyle changes for a vast number of individuals, most notably in the form of increased physical activity and diet alterations. The latter point is especially salient in a biochemical context, because of the myriad factors that can result in “fat accumulation”. Chief among these factors is the Perilipin 5A gene, (known as PLIN5A) which encodes the protein Perilipin 5A of the Perilipin family …

Mechanisms Of Ikbke Activation In Cancer, Sridevi Challa

USF Tampa Graduate Theses and Dissertations

Cancer is the second leading cause of death in the USA and it is expected to surpass heart diseases making it important to understand the underlying mechanisms of cancer. The efforts to target single signaling molecule showed little success in increasing the patient survival and it can be due to increased compensation for cell survival by alternative pathway activations. Hence comprehensive understanding of the alternative signaling pathways may help us treat cancer better. Chronic inflammation is attributed to increased risk of cancer and emerging studies show the growing importance of both canonical and non-canonical IκB kinases such as IKKα, IKKβ, …

Cyclipostins And Cyclophostin Analogs As Promising Compounds In The Fight Against Tuberculosis, Phuong Nguyen, Vincent Delorme, Anaïs Bénarouche, Benjamin Martin, Rishi Paudel, Giri Gnawali, Abdeldjalil Madani, Rémy Puppo, Valérie Landry, Laurent Kremer, Priscille Brodin, Christopher Spilling, Jean-François Cavalier, Stéphane Canaan

Chemistry & Biochemistry Faculty Works

A new class of Cyclophostin and Cyclipostins (CyC) analogs have been investigated against Mycobacterium tuberculosis H37Rv (M. tb) grown either in broth medium or inside macrophages. Our compounds displayed a diversity of action by acting either on extracellular M. tb bacterial growth only, or both intracellularly on infected macrophages as well as extracellularly on bacterial growth with very low toxicity towards host macrophages. Among the eight potential CyCs identified, CyC 17 exhibited the best extracellular antitubercular activity (MIC50 = 500 nM). This compound was selected and further used in a competitive labelling/enrichment assay against the activity-based probe Desthiobiotin-FP in order …

Cyclipostins And Cyclophostin Analogs As Promising Compounds In The Fight Against Tuberculosis, Phuong Chi Nguyen, Vincent Delorme, Anaïs Bénarouche, Benjamin P. Martin, Rishi Paudel, Giri R. Gnawali, Abdeldjalil Madani, Rémy Puppo, Valérie Landry, Laurent Kremer, Priscille Brodin, Christopher D. Spilling, Jean-François Cavalier, Stéphane Canaan

Christopher Spilling

Arsenite Resistance Of Euglena Mutabilis, Nicole Loumarinett Rosendo Mercado, Doug G. Cole (Mentor)

Idaho Conference on Undergraduate Research

Euglena are photosynthetic unicellular protozoa. Commonly found in rivers, lakes and ponds, some Euglena are found in toxic environments, like areas of acid mine drainage where they can grow at low pH and in the presence of heavy metals and metalloids such as arsenite (e.g. Euglena mutabilis). The goal of this research is to determine if an Idaho Euglena isolate (SG6) belongs to the E. mutabilis species and to compare it’s level of arsenite resistance with other E. mutabilis strains. As part of the methodology, we have developed microtiter plate assays in which the cells are …

Phospholipase Dζ Enhances Diacylglycerol Flux Into Triacylglycerol, Wenyu Yang, Geliang Wang, Jia Li, Philip Bates, Xuemin Wang, Douglas Allen

Biology Department Faculty Works

Plant seeds are the primary source of triacylglycerols (TAG) for food, feed, fuel, and industrial applications. As TAG is produced from diacylglycerol (DAG), successful engineering strategies to enhance TAG levels have focused on the conversion of DAG to TAG. However, the production of TAG can be limited by flux through the enzymatic reactions that supply DAG. In this study, two Arabidopsis phospholipase Dζ genes (AtPLDζ1 and AtPLDζ2) were coexpressed in Camelina sativa to test whether the conversion of phosphatidylcholine to DAG impacts TAG levels in seeds. The resulting transgenic plants produced 2% to 3% more TAG as a component of …

Phospholipase Dζ Enhances Diacylglycerol Flux Into Triacylglycerol, Wenyu Yang, Geliang Wang, Jia Li, Philip David Bates, Xuemin Wang, Douglas K. Allen

Xuemin (Sam) Wang

Understanding The Mechanism Of Oxidative Stress Generation By Oxidized Dopamine Metabolites: Implications In Parkinson's Disease, Nihar Mehta

Wayne State University Dissertations

Oxidation of dopamine to toxic metabolites is considered to be one of the prime factors involved in the death of dopaminergic neurons in Parkinson’s disease. Some dopamine oxidation products have the capability to redox cycle in the presence of molecular oxygen, further contributing to oxidative stress. Therefore, our aim here was to study the redox cycling of dopamine oxidized metabolites and elucidate the underlying mechanism by which they cause oxidative stress.

Redox reactions involve transfer of one or more electrons between two compounds

resulting in either oxidation or reduction. In redox cycling, a compound undergoes

alternate oxidation and reduction, transferring …