Life Sciences Commons^™

Metabolic Heterogeneity And The Roles Of Cody And Ccpa In Central Metabolism And S. Aureus Biofilm Formation., Logan L. Bulock

Theses & Dissertations

Staphylococcus aureus is a metabolically versatile human pathogen, causing disease in many areas of the body. Its versatility can be attributed to the fact that it utilizes a variety of tools to adapt to many different environments, including toxins to scavenge from the host and multiple transporters to compete for its preferred carbon sources. S. aureus can also survive in harsh conditions through biofilm development, which are notoriously recalcitrant to antibiotics and immune defenses. Biofilms exhibit marked heterogeneity, with division of labor for production of matrix components and differential gene expression among various niches within the biofilm.

In this study, …

Metabolic Regulation During Extraembryonic Endoderm Differentiation, Mohamed Gatie

Electronic Thesis and Dissertation Repository

The inner cell mass undergoes orchestrated cellular divisions resulting in the formation of the epiblast (EPI) and primitive endoderm (PrE). Understanding the process of cell fate specification is crucial to appreciate the intricacies of proper embryonic development. While the mouse embryo is an excellent model, limitations do exist with number, technical challenges, and accessibility, therefore, in my thesis I employed two cell-based models to recapitulate the EPI-PrE fate in vitro. Many signaling pathways have been implicated in this lineage decision, metabolism and its downstream products have been recently regarded as a driver of lineage commitment. Using various biochemical, molecular, …

Influence Of Additive Aiv-2000 And Pre-Wilted Big Bale On Silage Quality, Animal Performance And Rumen Metabolism, Jonas Jatkauskas, V. Vrotniakienė

IGC Proceedings (1997-2023)

Silage treatment with AIV-2000 or making of silage big bales resulted in a higher level of lactic acid and organic matter digestibilities and reduced concentrations of butyric acid and ammonia-N. Feeding AIV-2000 treated and big bale silages increased weight gains of young fattening bulls by, respectively, 5.44 and 6.77% in comparison with the ordinary made silage. AIV-2000 treated and big bale silages affected microflora activity in the rumen. Infusoria count was higher by 13.5 and 30.34% (P < 0.05), VFA concentration increased by 0.39 and 8.45%, the pH value decreased by 0.05 and 0.1 unit, the content of total nitrogen was by 14.67 and 18.73 mg/100 ml, protein nitrogen by 14.12 and 16.63 mg/100 ml and non-protein nitrogen by 0.53 and 1.39 mg/100 ml higher, respectively for AIV-2000 and big bale groups in comparison with the control group.

Editorial: The Metabolism Of The Neuron-Glia Unit, Yannick Poitelon, Lance A. Johnson, Marie-Ève Tremblay

Physiology Faculty Publications

No abstract provided.

Apoε4 Lowers Energy Expenditure In Females And Impairs Glucose Oxidation By Increasing Flux Through Aerobic Glycolysis, Brandon C. Farmer, Holden C. Williams, Nicholas A. Devanney, Margaret A. Piron, Grant K. Nation, David J. Carter, Adeline E. Walsh, Rebika Khanal, Lyndsay E. A. Young, Jude C. Kluemper, Gabriela Hernandez, Elizabeth J. Allenger, Rachel Mooney, Lesley R. Golden, Cathryn T. Smith, J. Anthony Brandon, Vedant A. Gupta, Philip A. Kern, Matthew S. Gentry, Josh M. Morganti, Ramon C. Sun, Lance A. Johnson

Physiology Faculty Publications

BACKGROUND: Cerebral glucose hypometabolism is consistently observed in individuals with Alzheimer's disease (AD), as well as in young cognitively normal carriers of the Ε4 allele of Apolipoprotein E (APOE), the strongest genetic predictor of late-onset AD. While this clinical feature has been described for over two decades, the mechanism underlying these changes in cerebral glucose metabolism remains a critical knowledge gap in the field.

METHODS: Here, we undertook a multi-omic approach by combining single-cell RNA sequencing (scRNAseq) and stable isotope resolved metabolomics (SIRM) to define a metabolic rewiring across astrocytes, brain tissue, mice, and human subjects expressing APOE4.

RESULTS: Single-cell …

The Regulation Of Plasmodium Falciparum Metabolism By Haloacid Dehalogenase Proteins, Philip Frasse

Arts & Sciences Electronic Theses and Dissertations

Malaria is an enormous financial and public health burden for much of the world, infecting over 200 million and killing over 400,000 people every year. While much progress has been made combating malaria in the past few decades, those advances have slowed in recent years, partially due to the emergence of resistance to all known antimalarials used to date. To achieve the goal of eliminating malaria as a major global health problem, new therapeutics need to be developed, targeting novel categories of parasite biology. One poorly understood area of parasite biology is the regulation of various metabolic pathways. We have …

Link Between Muscle And Whole-Body Energetic Responses To Exercise, Christopher M.T. Hayden

Masters Theses

Substantial evidence exists regarding how skeletal muscles use energy and how this affects muscular performance. What remains unclear is how characteristics of muscle energetics affect whole-body energetics during daily living, and what effects this may have on mobility. The goal of this study was to determine the associations between muscle and whole-body energetics including the relationships between: 1) muscle PCr depletion (∆PCr) in response to light intensity isotonic contractions and the oxygen deficit at the onset of a 30-min treadmill walk (30MTW), and, 2) muscle oxidative capacity and excess post-exercise oxygen consumption (EPOC; 30MTW), respiratory exchange ratio (RER; 30MTW), and …

Characterization And Modulatory Influence Of Pyruvate Kinase Muscle Isoforms 1 And 2 Within The Murine Pluripotent Continuum, Joshua G. Dierolf

Electronic Thesis and Dissertation Repository

Mouse embryonic stem cells (mESCs) and mouse epiblast stem cells (mEpiSCs) represent opposite ends of a pluripotency continuum, respectively referred to as naïve and primed pluripotent states. A third, recently discovered intermediate state has been described as the ‘formative state’. Metabolism has been traditionally regarded as a by-product of cell fate; however, recent evidence now supports metabolism as promoting stem cell fate. Pyruvate kinase muscle isoforms 1 and 2 (PKM1 and PKM2) catalyze the final, rate limiting step of glycolysis generating adenosine triphosphate (ATP) and pyruvate; however, the precise role(s) of these isozymes in naïve, formative, and primed pluripotency is …

Non-Reductionist Science: Assessing Metabolism And Entropy With Systems Theory And Hegelian Logic, Tre Schumacher

Undergraduate Research

This paper will offer Hegelian logic, its connection with systems theory, and how it can serve as a replacement for reductionism in the sciences. First, the connection will be made between formal logic and reductionism. Second, systems theory will be introduced as an alternative to reductionism. Third, Hegelian logic and its connection with systems theory will be demonstrated. Fourth, a non-reductionist mode of science will be offered, wherein Hegelian logic and systems theory can work alone or together, in replacement of reductionism and formal logic. Last, a brief sample of this mode of science will be shown in an examination …

Physiological And Metabolic Strain Differences In Response To Constant Light In Male Mice, Hannah V. Deane

Honors Program Theses and Projects

Circadian rhythms, located in all organisms, is an innate natural clock system driving daily cycles in behavior and metabolism. This clock entrains to daily cycles via regular exposure to light:dark cycles. When light exposure is altered, it is known to cause alterations behavior and metabolism because of its role in regulating bodily function. Constant light (LL) is emerging as a predominant circadian disruption due to prolonged exposure to light at night during night-shift work, and the use of TVs and smartphones at night and throughout the night. To understand how different organisms respond to constant light, two comparative studies were …

Decreased Activity Of Phosphofructokinase-1 In Flight Muscle Cells Of Hawk Moth Manduca Sexta With Age, Owen G. Alvine

Honors Thesis

The phosphofructokinase-1 (PFK-1) enzyme is important for the catalyzation and regulation of glycolysis, especially in muscle. Investigating age-related changes in PFK-1 activity will provide insights into the metabolism shifts in muscle cells of our muscle aging model. The hawk moth, Manduca sexta, was chosen as the model organism because of its unique endothermic, synchronous flight muscles that are more analogous to vertebrates than invertebrate species. We hypothesized that PFK-1 activity will increase in muscle cells of aged moths due to dysregulation of the mitochondria. This was predicted to change the method of energy production, by hindering oxidative phosphorylation, making glycolysis …

Catabolism Of Bcaas And Application, Skylar Arellano-Myers

Honors Thesis

Over the past 150 years, amino acids have been found and researched in the nutrition biochemistry field. Over these years, three have been identified; leucine, valine and isoleucine; to make up the branch chain amino acids (BCAAs) that play a crucial role on the anaerobic and aerobic energy systems. The metabolism of BCAAs is a highly complicated process that is regulated by the activation of the alpha-keto acids dehydrogenase complex (BCKDH complex) to complete the catabolic reaction. With exercise, it has been found to increase the metabolism of BCAAs by increasing the BCKDH complex, which will decrease the fatigue and …

How Acetylation Regulates Metabolic Enzyme Function During Environmental Shifts, Jared Canonigo

Biological Sciences Undergraduate Honors Theses

Organisms such as Saccharomyces cerevisiae can regulate the mechanisms of proteins through post-translational modification. These modifications play a vital role in functional proteomic activity because they can regulate protein activity, localization, and interaction with other cellular molecules. Such modifications include phosphorylation, methylation, and acetylation. The metabolic mechanisms of yeast became of keen interest to our lab because our lab noticed many stress defense proteins were being acetylated during stress heat shock. Notably, Adh1p and Adh2p showed both an increase and a decrease in acetylation at two lysine residues (K315 and K314) overtime during heat shock respectively, though the exact function …

Interregulation Between Msaabcr Operon And Ccpe To Determine Staphylococcal Metabolism And Virulence, Erin R. Cox

Honors Theses

Staphylococcus aureus is a complex human pathogen that causes problems in both healthcare and community settings. Staphylococcus aureus is a gram-positive, sphere shaped bacterium that usually colonizes in the nasal cavity of healthy individuals. Staphylococcus aureus infections are a growing health concern due to its ability to produce virulence factors, such as pigmentation, protease production, and capsule formation. Two regulators in S. aureus virulence factors are msaABCR, which is a newly characterized operon, and ccpE. In order to determine the interaction between these two regulators in regulating virulence and metabolism in S. aureus, ccpE and ccpE/ …

Study Of The Role Of The Msaabcr Operon In Tricarboxylic Acid Cycle Activity And Persister Cell Formation In Staphylococcus Aureus, Karsen Motter

Honors Theses

Staphylococcus aureus is an important human pathogen that causes wide arrays of infections ranging from minor skin infections to lethal systemic conditions such as infective endocarditis, osteomyelitis, sepsis and pneumonia. These systemic diseases are often difficult to treat due to the presence of persister cells. Persister cells are a phenotypic variant of the bacterial population that exhibit extreme and transient antibiotic tolerance accompanied by a transient halt in growth. Upon cessation of antibiotic treatment, however, persisters resume growth which results in recurrence of infections. This characteristic of persister cells therefore displays high clinical significance. In this study, we show the …

A Computational Analysis Of Selective Metabolism Of Bupropion By Cytochrome P450 2b6, Alyssa Santos

Honors Scholar Theses

Bupropion is an antidepressant and smoking cessation aid that is extensively metabolized by cytochrome P450 (CYP) 2B6. It is a highly lipophilic chiral drug that undergoes stereoselective metabolism with preference for the (S)-enantiomer. Despite chemical reasons for why bupropion can be metabolized by other CYP isozymes, clinically, bupropion is preferentially metabolized by CYP2B6, and at certain concentrations, CYP2E1, CYP2C19, and CYP3A4. A computational analysis with simulated molecular docking was performed using two different scoring algorithms to analyze the specific amino acid interactions between bupropion and various CYP isozymes. Trials were run using one stereoisomer of bupropion (R …

Differential Gene Expression In Starvation Selected Drosophila Melanogaster, Katherine Schultz

UNLV Theses, Dissertations, Professional Papers, and Capstones

Fruit flies that have been selected for starvation resistance can be used in experimental studies to study physiological processes. Both their genomes and their phenotypes, especially metabolism, change significantly as a result of artificial selection. Starvation selected flies develop slower and are larger due to higher lipid content as adults. We used RNAseq to study gene expression in third instar larval fat body tissue from selected and control lines at the same chronological time point, when the fed control (“FC”) lines were wandering, and the starvation selected (“SS”) lines were in the third larval instar but not yet wandering due …

Investigating A Novel Function For Phosphoserine Aminotransferase 1 (Psat1) In Epidermal Growth Factor Receptor (Egfr)-Mediated Lung Tumorigenesis., Rumeysa Biyik-Sit

Electronic Theses and Dissertations

Phosphoserine aminotransferase 1 (PSAT1) catalyzes the second enzymatic step within the serine synthetic pathway (SSP) and its expression is elevated in numerous human cancers, including non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutant NSCLC is characterized by activating mutations within its tyrosine kinase domain and accounts for 17% of lung adenocarcinomas. Although elevated SSP activity has been observed in EGFR-mutant lung cancer cells, the involvement of PSAT1 in EGFR-mediated oncogenesis is still unclear. Here, we explore a putative non-canonical function for PSAT1 using biochemical approaches to elucidate unknown interacting proteins and genomic RNA-seq profiling to identify cellular …

Construction And Analysis Of Three Multi-Partite Synthetic Microbial Communities, Alexander J. Lazzara, Jacob K. Fanning

Honors Theses

Microbial Communities are of interest to molecular biologists hoping to understand the nature of metabolic interactions between co-existing, or possibly mutualistic, organisms. These interactions are ubiquitous in nature, but understanding the molecular mechanisms involved remains challenging and not well understood. Here, we design three tri-partite microbial circuits based on possible interactions among involved microbes, which are discussed and may suggest mutualistic interactions. Carbon and nitrogen molecular pathways and the intracellular metabolism of each microbe is discussed. We present minimal growth media that will ensure that organisms utilize available resources, which may originate from metabolic processes in neighboring microbes, simulating a …

Evolution And Selection: From Suppression Of Metabolic Deficiencies To Bacteriophage Host Range And Resistance, Daniel Kurt Arens

Theses and Dissertations

The evolution and adaptation of microorganisms is so rapid it can be seen in the time frame of days. The root cause for their evolution comes from selective environmental pressures that see organisms with beneficial mutations survive otherwise deadly encounters or outperform members of its population who fail to adapt. This does not always result in strict improvement of the individual as in the case of antibiotic resistant bacteria who often display fitness tradeoffs to avoid death (see Reviews [1-3]). For example, when an ampicillin resistance gene (ampC) containing plasmid that is occasionally found in the wild was transformed into …

Carbon Dots For Specific “Off-On” Sensing Of Co2+ And Edta For In Vivo Bioimaging, Xiangping Wen, Guangming Wen, Wenyan Li, Zhonghua Zhao, Xine Duan, Wenjun Yan, John F. Trant, Yingqi Li

Chemistry and Biochemistry Publications

Fluorescent carbon dots (CDs) were hydrothermally synthesized from a mixture of frozen tofu, ethylenediamine and phosphoric acid in an efficient 64% yield. The resulting CDs exhibit good water solubility, low cytotoxicity, high stability, and excellent biocompatibility. The CDs selectively and sensitively detect Co2+ through fluorescent quenching with a detection limit of 58 nM. Fluorescence can be restored through the introduction of EDTA, and this phenomenon can be used to quantify EDTA in solution with a detection limit of 98 nM. As both analytes are detected by the same CD platform, this is an “off-on” fluorescence sensor for Co2+ and EDTA. …

Metabolic Reprogramming By Dna Tumour Viruses, Martin Prusinkiewicz

Electronic Thesis and Dissertation Repository

Viruses are the etiological agents of approximately 12% of human cancers. However, only a subset of viral infections eventually progress to cancer. As obligate intracellular parasites, viruses create a host-cell environment that is amenable to virus replication. These changes to host-cell processes during infection are enacted by virally-encoded proteins that act as molecular hubs. When these processes intersect with pathways that encourage the development of cancer, such as the p53 tumour suppressor pathway, these virally-encoded molecular hub proteins function as viral oncoproteins. One major requirement of both virus infected cells and rapidly growing cancer cells is an altered metabolism that …

Dark Chocolate Supplementation Elevates Resting Energy Expenditure In Exercise Trained Females, Katie M. Presler, Michael Webster

International Journal of Exercise Science

International Journal of Exercise Science 14(2): 250-259, 2021. Several recent reports have indicated positive health and exercise benefits of (-)-epicatechin-rich cocoa products. This study investigated the influence of dark chocolate (DC) supplementation on resting and steady state exercise metabolism in a group of athletically fit females. Using a randomized, single-blind design, 18 exercise trained female subjects were assigned to a 30-d supplementation with either 20g· d^-1 of 70% DC (n = 9) or a calorically matched white chocolate (WC) (n = 9). Pre-supplementation (PRE), subjects underwent indirect calorimetry assessment for resting energy expenditure (REE) and exercise energy …

Caffeine Modulation Of Attention And Focus In Task Performance, Claudia R. Berger

Dissertations, Theses, and Capstone Projects

Caffeine has been a heavily researched drug for decades given its prevalence in global consumption, as well as its large impacts on metabolic and executive function research alike. The present study aims to combine a behavioral study (Experiment 1) with a feasibility study (Experiment 2) to test the impacts of variable caffeine consumption on task performance. For both studies, participants filled out a questionnaire regarding caffeine use. Experiment 1 examined whether caffeine modulated attention in an online behavioral task in which participants were asked to identify a target (e.g., female “ahpa”). Participants were tested twice once after consuming 12 ounces …

The Effects Of Temperature And Body Size On The Metabolism And Hypoxia Tolerance Of White Abalone (Haliotis Sorenseni) And Red Abalone (H. Rufescens), Stephanie Fan

Theses

In 2001, white abalone, Haliotis sorenseni, became the first marine invertebrate to be listed under the U.S. Endangered Species Act. Allee effects due primarily to overharvesting and disease resulted in individuals being too far apart for successful fertilization. Despite the fishery closure in 1996, H. sorenseni still shows no signs of recovery. Today, the White Abalone Recovery Consortium (WARC), a group that includes federal and state agencies, aquaculture organizations, academic institutions, and public aquaria, is working to recover this endangered species back from the brink of extinction.

In order to better understand the metabolic demands and hypoxia tolerance of the …

Regional N-Glycan And Lipid Analysis From Tissues Using Maldi-Mass Spectrometry Imaging, Alexandra E. Stanback, Lindsey R. Conroy, Lyndsay E. A. Young, Tara R. Hawkinson, Kia H. Markussen, Harrison A. Clarke, Derek B. Allison, Ramon C. Sun

Neuroscience Faculty Publications

N-glycans and lipids are structural metabolites that play important roles in cellular processes. Both show unique regional distribution in tissues; therefore, spatial analyses of these metabolites are crucial to our understanding of cellular physiology. Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) is an innovative technique that enables in situ detection of analytes with spatial distribution. This workflow details a MALDI-MSI protocol for the spatial profiling of N-glycans and lipids from tissues following application of enzyme and MALDI matrix.

For complete details on the use and execution of this protocol, please refer to Drake et al. (2018) and Andres et al. (2020).

Acetic Acid Supplementation: Effect On Resting And Exercise Energy Expenditure And Substrate Utilization, Kolton M. Cobb, Domenico A. Chavez, Jonathan D. Kenyon, Zachary J. Hutelin, Michael Webster

International Journal of Exercise Science

International Journal of Exercise Science 14(2): 222-229, 2021. The purpose of this study was to investigate the influence of acetic acid (apple cider vinegar; ACV) supplementation on resting and exercise energy expenditure and substrate utilization. Using a randomized, double blind, crossover design, 16 healthy subjects were supplemented for 4 d with either ACV (30-ml/d) mixed in 1 L of a non-nutritive lemon-flavored drink or a placebo (PLA). They were then assessed via indirect calorimetry for resting energy expenditure (REE) and substrate utilization. This was immediately followed by the assessment of steady state cycling exercise energy expenditure at 40 W (EEE-40) …

Homeostatic T Cell Receptor Interactions With Self-Peptide Tune Cd4+ T Cell Function, Juliet Marie Bartleson

Arts & Sciences Electronic Theses and Dissertations

Homeostatic T Cell Receptor Interactions with Self-Peptide Tune CD4+ T Cell Function

by

Juliet Marie Bartleson

Doctor of Philosophy in Biology and Biomedical Sciences

Immunology

Washington University in St. Louis, 2021

Professor Paul M. Allen, Chair

Mature CD4+ T cells circulate throughout peripheral secondary lymphoid organs using their T cell receptor (TCR) to surveil peptide presented on major histocompatibility complex class II molecules (pMHC) in search of cognate, antigenic peptide. In the absence of an immune challenge, however, the TCR is continuously interacting with self-pMHC, which induces a relatively weak TCR signal known as tonic signaling. These homeostatic TCR:self-pMHC interactions …

Mitochondria Exert Age-Divergent Effects On Recovery From Spinal Cord Injury, Andrew N. Stewart, Katelyn E. Mcfarlane, Hemendra J. Vekaria, William M. Bailey, Stacey A. Slone, Lauren A. Tranthem, Bei Zhang, Samir P. Patel, Patrick G. Sullivan, John C. Gensel

Physiology Faculty Publications

The extent that age-dependent mitochondrial dysfunction drives neurodegeneration is not well understood. This study tested the hypothesis that mitochondria contribute to spinal cord injury (SCI)-induced neurodegeneration in an age-dependent manner by using 2,4-dinitrophenol (DNP) to uncouple electron transport, thereby increasing cellular respiration and reducing reactive oxygen species (ROS) production. We directly compared the effects of graded DNP doses in 4- and 14-month-old (MO) SCI-mice and found DNP to have increased efficacy in mitochondria isolated from 14-MO animals. In vivo, all DNP doses significantly exacerbated 4-MO SCI neurodegeneration coincident with worsened recovery. In contrast, low DNP doses (1.0-mg/kg/day) improved tissue …

In Vivo Optical Metabolic Imaging Of Long-Chain Fatty Acid Uptake In Orthotopic Models Of Triple-Negative Breast Cancer, Megan C. Madonna, Joy E. Duer, Joyce V. Lee, Jeremy Williams, Baris Avsaroglu, Caigang Zhu, Riley Deutsch, Roujia Wang, Brian T. Crouch, Matthew D. Hirschey, Andrei Goga, Nirmala Ramanujam

Biomedical Engineering Faculty Publications

Targeting a tumor’s metabolic dependencies is a clinically actionable therapeutic approach; however, identifying subtypes of tumors likely to respond remains difficult. The use of lipids as a nutrient source is of particular importance, especially in breast cancer. Imaging techniques offer the opportunity to quantify nutrient use in preclinical tumor models to guide development of new drugs that restrict uptake or utilization of these nutrients. We describe a fast and dynamic approach to image fatty acid uptake in vivo and demonstrate its relevance to study both tumor metabolic reprogramming directly, as well as the effectiveness of drugs targeting lipid metabolism. Specifically, …