Biochemistry, Biophysics, and Structural Biology Commons^™

Using Nmr Spectroscopy And Computational Chemistry To Confirm The Structure Of Novel Antibiotic Nocamycin O, Stephanie Lewis

CMC Senior Theses

In recent years, many medically promising antibiotics have been discovered in nature, especially in insect-microbe symbioses. One of the better-studied examples of this kind of defensive relationship is that of fungus-growing ants and the antibiotic-producing Actinobacteria. These bacteria produce several defensive chemicals with myriad uses, including one antibiotic that inhibits the growth of several bacterial strains, including other Actinobacteria. This antibiotic (known as nocamycin O) is a promising candidate for medicinal use due to its similarities to bacterial RNA polymerase inhibitors tirandamycin and streptolydigin, which inhibit several human pathogens. The determination of the structure of nocamycin O will be an …

Female And Male-Controlled Livestock Holdings Impact Pastoralist Food Security And Women’S Dietary Diversity, Henriette Gitungwa, Christopher Gustafson, E.Y. Jimenez, E. Wesley F. Peterson, M. Mwanzalila, Asha Makweta, E. Komba, R.R. Kazwala, J.A.K. Mazet, Elizabeth Vanwormer

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: Food insecurity is a global problem that requires a One Health approach. As many households in low- and middle-income nations rely on crops and livestock that they produce to meet their household’s needs, food security and nutrition are closely linked to the health of animals and the environment. Resources controlled by women are more often allocated to uses that benefit the entire household, such as food, health, and educating children, than men’s resources. However, studies of gender control of resources among pastoralist societies are scant. We examined the effect of female and male control of livestock resources on food …

Use Of Small Molecule Fanconi Anemia Pathway Inhibitors As Sensitizing Agents To Laromustine., Sam W. Marchant

Honors Theses

Laromustine is an experimental chemotherapeutic sulfonyl hydrazine prodrug shown in clinical trials to be effective against acute myeloid leukemia. The mechanism of action of laromustine involves interstrand crosslinking, via chloroethylation, and enzyme inhibition, caused by carbamoylation. The work described herein aims to investigate whether inhibition of the replication-dependent interstrand crosslink repair Fanconi Anemia pathway further sensitizes cells to laromustine. By measuring metabolic activity immediately after drug exposure, we find laromustine to be equally as cytotoxic towards Fanconi Anemia deficient and wild type cells. However, through clonogenic assays we show Fanconi Anemia mutations sensitize cells to laromustine’s anti-proliferative effect. Furthermore, we …

Functional Characterization Of Threonine 49 Phosphorylation Of Cytochrome C, Antoine Khobeir

Wayne State University Theses

Cytochrome c (Cytc) is a pivotal multifunctional mitochondrial protein that serves as a single electron carrier between complexes III and IV of the electron transport chain. It has important roles in both cellular respiration and apoptosis. The novel Thr49 (T49) phosphorylation of Cytc likely affects mitochondrial respiration, membrane potential, ROS production, ATP production, and apoptosis. Based on the functional characterization of previously mapped phosphorylation sites (Tyr97, Tyr48, Thr28, Ser47, Thr58) of the lab, we hypothesize that T49 phosphorylation will lead to controlled respiration, optimal intermediate mitochondrial membrane potential, lower ROS production, and inhibition of apoptosis compared to unphosphorylated Cytc. Here …

Novel Role Of Endoplasmic Reticulum-Associated Degradation In The Regulation Of Ceruloplasmin, Stephen William Hippleheuser

Wayne State University Theses

Ceruloplasmin (Cp) is a secreted ferroxidase produced by the hepatocytes that assists in the transport of iron throughout the human body. In human aceruloplasminemia patients, due to Cp deficiency excess intracellular iron buildup leads to ailments like liver cirrhosis, neurodegeneration, and blindness. We recently found that the biogenesis of Cp in the endoplasmic reticulum (ER) is regulated by a principal ER quality-control process, ER-associated degradation (ERAD). ERAD clears misfolded ER proteins for cytosolic proteasomal degradation, with the Sel-1 suppressor of lin-12-like (Sel1L)-HMG-CoA reductase degradation 1 (Hrd1) protein complex representing the most conserved branch in mammals. Interestingly, we found that Sel1L-Hrd1 …

College Of Natural Sciences 2021 Year-End Publication, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

Page 2 Welcome, Table of Contents
Page 3 Our Departments: Highlights From 2021
Page 4 Overview of the College
Page 5 Overview of Bold & Blue
Pages 6, 7 Announcing the First Endowed Professorship in the College of Natural Sciences
Page 8 Spooky Science, Astronomy Outreach, SDSU Chemistry Research Features on Journal Cover
Page 9 Students Win Business Plan Competition With Aims to Improve Shelf Life of Produce, Summer Researchers
Page 10 NIH Grant Helps Unravel Rare Inflammatory Genetic Disorders, International Excellence in South Dakota
Page 11 The Next Frontier of Science Education: Virtual Reality, SDSU Researchers Uncover how Cancer …

Metabolite Profile And Biological Activities Of Crude Early Immature Durian Durio Zibethinus Fruit Extracts, Putthamas Pewlong

Chulalongkorn University Theses and Dissertations (Chula ETD)

Durian (Durio zibethinus) is a popularly consumed fruit in Thailand. To maintain the quality of fruit including size and taste, lots of early immature durian fruit (30-45 days after anthesis) were thinned. Therefore, the fruit at this stage is considered as an agricultural waste and there is no study focusing on this waste yet. The aim of the present study was to investigate the metabolite profile and biological activities related to human skin and hair dermal papilla cells. Four groups of primary metabolites (sugars, organic acids, amino acids, and miscellaneous) were annotated using GC-MS, meanwhile HPLC-Q-TOF-MS/MS analysis was performed to …

Lonidamine Is A Novel Inhibitor Of Fatty Acid Oxidation, Tianhai He

Theses and Dissertations

In this thesis project, we examined the hypothesis that lonidamine is an effective inhibitor of FAO in mammalian cells, underling its inhibitory effects on bioenergetic production and anti-cancer action. We compared its effects on FAO and glycolysis in multiple human cancer cell lines of different lineages.

Characterization Of A Label-Free Fluorescent Assay For Point Mutation Discrimination Based On Split Aptamer Probes, Shannon A. Beaton

Honors Undergraduate Theses

Due to the misuse of antibiotics, multi-drug resistant (MDR) bacteria have become more rampant in our society; these MDR have given rise to diseases that are not readily curable. One such agent is the Mycobacterium tuberculosis complex, which is a causative agent of tuberculosis (TB). Timely diagnostics of the bacterial infection and detection of bacterial drug-susceptibility profiles helps to initiate the necessary treatment in a timely fashion and to limit transmission of the disease. For more affordable detection of bacterial diseases, such as TN, tag-free split aptamer probes are advantageous. This proposal aims at designing split aptamer probes for detection …

Photoreceptor Phosphodiesterase (Pde6): Activation And Inactivation Mechanisms During Visual Transduction In Rods And Cones, Rick H. Cote

Faculty Publications

Rod and cone photoreceptors of the vertebrate retina utilize cGMP as the primary

intracellular messenger for the visual signaling pathway that converts a light stimulus into an electrical response. cGMP metabolism in the signal-transducing photoreceptor outer segment reflects the balance of cGMP synthesis (catalyzed by guanylyl cyclase) and degradation (catalyzed by the photoreceptor phosphodiesterase, PDE6). Upon light stimulation, rapid activation of PDE6 by the heterotrimeric G-protein (transducin) triggers a dramatic drop in cGMP levels that lead to cell hyperpolarization. Following cessation of the light stimulus, the lifetime of activated PDE6 is also precisely regulated by additional processes. This review summarizes …

Photoreceptor Phosphodiesterase (Pde6): Structure, Regulatory Mechanisms, And Implications For Treatment Of Retinal Diseases, Rick H. Cote, Richa Gupta, Michael J. Irwin, Xin Wang

Faculty Publications

The photoreceptor phosphodiesterase (PDE6) is a member of large family of Class I phosphodiesterases responsible for hydrolyzing the second messengers cAMP and cGMP. PDE6 consists of two catalytic subunits and two inhibitory subunits that form a tetrameric protein. PDE6 is a peripheral membrane protein that is localized to the signaling-transducing compartment of rod and cone photoreceptors. As the central effector enzyme of the G-protein coupled visual transduction pathway, activation of PDE6 catalysis causes in a rapid decrease in cGMP levels that results in closure of cGMP-gated ion channels in the photoreceptor plasma membrane. Because of its importance in the phototransduction …

Interactions Of Post-Pks Enzymes Of The Mithramycin Biosynthetic Pathway, Ryan Wheeler

Theses and Dissertations--Pharmacy

Combinatorial biosynthesis is a powerful tool for generating new, more active drug analogues to combat disease. But in order for combinatorial biosynthesis to be employed to its full potential, a deep understanding of the enzymes that produce the parent molecule must be had. The goals of the work presented in this thesis are to characterize the reaction catalyzed by MtmW, the final enzyme in the mithramycin (MTM) biosynthetic pathway, and to discover the interaction between MtmW and MtmOIV.

MtmW is an aldol-ketoreductase responsible for reducing the most distal carbonyl on the MTM pentyl side chain. It forms an octamer that …

Abc Transporters In Glioblastoma: Anticancer Drug Transport And Transporter Regulation At The Blood-Brain Barrier, Julia A. Schulz

Theses and Dissertations--Pharmacy

Glioblastoma is one of the deadliest cancers, with a median survival of only one year. Even after aggressive treatment consisting of surgical resection, radiation, and chemotherapy, most glioblastoma patients suffer from tumor recurrence within 6-9 months. One reason for treatment failure of anticancer drugs is the blood-brain barrier that protects the brain by impeding xenobiotic uptake from the blood. To this end, efflux transporters at the human blood-brain barrier, such as P-glycoprotein (ABCB1) and Breast Cancer Resistance Protein (ABCG2), prevent many compounds, including anticancer drugs, from entering the brain. Thus far, approaches to deliver anticancer drugs across the blood-brain barrier …

An Integrative Analysis On The Role Of Notch1 And Notch3 In Musculoskeletal Disease, Haydee Magdalena Torres

Electronic Theses and Dissertations

Notch signaling is an evolutionarily conserved signaling pathway involved in cell fate decisions and cell renewal of multiple systems, including skeletal and muscle homeostasis. As the multifunctional nuclear complex of Notch1 is essential for its pathological function, identifying these interacting partners represents a potentially broad range of druggable vulnerabilities. We have completed a BioID proteomics study and found a large set of nuclear proteins associated with NOTCH1, including transcriptional regulators and epigenetic modulators, of which Histone Deacetylase 1 (HDAC1) is a promising interacting partner of Notch1. Our Cytoscape analysis predicted HDAC1 to be a top critical node in an activated …

The Role Of Inflammasome In Vascular Remodeling Following Injury, Ted Amadi

Honors Theses

The purpose of the project presented in this thesis is to assess the contribution of inflammasome activation in mediating vascular wall remodeling that occurs following carotid artery injury due to decreased blood flow. To examine this, we used a mouse model of carotid artery ligation in mice lacking the expression of a key mediator of the inflammasome signaling pathway. Following ligation, we completed a histological assessment to compare the degree of the neointima formation and expression of inflammasome related proteins in both injured and the non-injured contralateral carotid artery in both wild-type (WT) and Caspase 1 knockout mice (Cas1 -/-).

Characterization Of Bpa Sensitive Strains In C. Elegans, Giulianna I. Escobar

Honors Theses

Bisphenol A (BPA) has been present in our environment since 1891 when it was first synthesized by Aleksandr Dianin. BPA has since been a topic of interest due to the possibility of diseases associated in human consumption of the chemical. Interestingly, Caenorhabditiselegans, commonly known as C.eleganshave shown to be able to tolerate the chemical. Thisorganism is an advantageous model organism for research since they are simple organisms to study, cheap, produce a large brood size, and have a short life cycle. Previously a forward genetic screen was done to isolate 2000 healthy strains in order to determine which strains showed …

'Induction Of Apoptosis, Cytotoxicity And Radiosensitization By Novel 3,4-Dihydroquinazolinone Derivatives, Eman Ramadan, Amira Khalil

Pharmacy

Twenty new quinazolinone derivatives bearing a piperonyl moiety were designed and synthesized. The structures of the target compounds were in agreement with the microanalytical and spectral data. Compounds 4-10, 13, 14 and 17-27 were screened for their cytotoxic activity against HepG-2 and MCF-7 cancer cell lines. The target compounds showed IC₅₀ in the range of 2.46-36.85 µM and 3.87-88.93 µM for HepG-2 and MCF-7, respectively. The promising compounds 7, 19, 26 and 27 were selected to measure their EGFR inhibitory activity. The IC₅₀ values of the promising compounds were in the range of 146.9-1032.7 nM for EGFR in …

Post-Translational Modification And Degradation Mechanisms Of The Aryl Hydrocarbon Receptor, Yujie Yang

University of the Pacific Theses and Dissertations

The aryl hydrocarbon receptor (AHR) is a transcription factor first discovered to be activated by exogenous ligands, such as dioxins, and helps promote downstream gene (e.g. CYP1A1) transcription to metabolize the toxicants. With the reports of various AHR targets genes, the expression levels and activities of AHR have been implicated in many physiological and pathological situations. Understanding how AHR protein level is regulated would provide more information to target AHR. AHR stays in the cytosol in the absence of ligand in a complex with HSP90, p23 and XAP2. After ligand activation, AHR translocates into the nucleus, fulfilling its transactivation function …

Soil Moisture And Porosity Affects The Abundance And Distribution Of Ageratum Houstonianum, Sahar Fattani, Christabel-Anne Forka, Monique Garcia, Thao Huynh, Torre Merricks, Morgan Robinson, Charcacia Sanders

Pursue: Undergraduate Research Journal

Introduction: Ageratum houstonianum is an herbaceous, drought-tolerant plant also known as Blue billygoat weed. It grows well in drained soil and shaded areas. Soil moisture and porosity are two abiotic factors that affect the abundance and distribution of A. houstonianum. An ideal condition for plants to grow includes a greater amount of soil moisture and porosity. Higher porosity would mean that there is a greater number of pores, which would result in more significant plant nutrients because of its ability to retain more water. The purpose of this research was to see how soil moisture and porosity based on …

Comparison Of Standard And Environmental Dna Methods For Estimating Chinook Salmon Smolt Abundance In The Klamath River, California, Doyle Joseph Coyne

Cal Poly Humboldt theses and projects

Evaluating abundance of juvenile salmonids is critical to conservation and management. Current abundance estimation involves use of rotary screw traps and mark-recapture studies. Use of environmental DNA (eDNA) in water samples offers a noninvasive and less expensive approach that may potentially improve or eventually replace traditional monitoring. Here I evaluate the utility of eDNA to predict weekly abundance estimates of outmigrating Chinook salmon (Oncorhynchus tshawytscha) smolts in the Klamath River, California. A total of 15 water samples were collected per week over the 17-week smolt outmigration in both 2019 and 2020. Chinook salmon eDNA concentration in each water …

Sars-Cov-2: An Investigation On Mutagenicity And Its Effects On Infectivity And Mortality, Tyler Elliott Silverwood

Honors Theses and Capstones

SARS-CoV-2, the etiological agent of the COVID-19 pandemic, has rapidly become a worldwide public health concern. Classified as a betacoronavirus, it is the third human coronavirus (HCoV) to emerge in the 21st century that causes severe disease, alongside SARS-CoV and MERS-CoV. The genome consists of open reading frames encoding accessory proteins and four structural proteins, including the spike protein which is a key determinant of host cell tropism. Mutations within the genome, particularly the spike gene, have been linked in-vitro to increased binding affinity to the human receptor angiotensin-converting enzyme 2 (hACE2), increased fitness in human hosts, and immune evasion. …

Biocompatible And Multifunctional Trityl Spin Probes For Electron Paramagnetic Resonance Spectroscopy, Teresa D. Gluth

Graduate Theses, Dissertations, and Problem Reports (ETD)

The primary objective of my thesis was to develop and utilize a biocompatible multifunctional trityl spin probe for concurrent measurement of pO₂, pH_e, and [P_i] in vivo by electron paramagnetic resonance (EPR) spectroscopy (Chapter 2). My first goal was to synthesize the proposed probe we are terming HOPE71. Secondly, HOPE71 was characterized by X-band and L-band EPR spectroscopy. Next, the biocompatibility of HOPE71 was assessed through an albumin binding test, cytotoxicity assays, and in vivo intravenous tolerance. Then, the use of HOPE71 to measure the target parameters was demonstrated in a breast cancer …

An Investigation On The Regulation Of The Tweak–Fn14–Nf-Kb Pathway, Jawahar Khetan

Doctoral Dissertations

“Dysregulation of inflammatory pathways is strongly implicated in cancers and autoimmune diseases. The most consequential of these pathways involves the nuclear translocation of NF-kB, a transcription factor that induces the transcription of multiple proteins associated with cell survival, inflammation, proliferation and death. It is activated when the fibroblast growth factor-inducible 14 kDa protein (Fn14), a trimeric receptor recruits its ligand, TWEAK. Studies have shown that Fn14 is over-expressed in many tumors, the aggressiveness of which is often correlated with the degree of upregulation. Furthermore, TWEAK-Fn14 activation has been shown to result in persistent NF-kB activation. Using a mechanistic model of …

Impact Of The Histidine‐Containing Phosphocarrier Protein Hpr On Carbon Metabolism And Virulence In Staphylococcus Aureus, Linda Pätzold, Anne-Christine Brausch, Evelyn-Laura Bielefeld, Lisa Zimmer, Greg A. Somerville, Markus Bischoff, Rosmarie Gaupp

School of Veterinary and Biomedical Sciences: Faculty Publications

Carbon catabolite repression (CCR) is a common mechanism pathogenic bacteria use to link central metabolism with virulence factor synthesis. In gram‐positive bacteria, catabolite control protein A (CcpA) and the histidine‐containing phosphocarrier protein HPr (encoded by ptsH) are the predominant mediators of CCR. In addition to modulating CcpA activity, HPr is essential for glucose import via the phosphotransferase system. While the regulatory functions of CcpA in Staphylococcus aureus are largely known, little is known about the function of HPr in CCR and infectivity. To address this knowledge gap, ptsH mutants were created in S. aureus that either lack the open reading …

An Evaluation Of The Anti-Carcinogenic Response Of Major Isothiocyanates In Non-Metastatic And Metastatic Melanoma Cells, Melina Mitsiogianni, Sotiris Kyriakou, Ioannis Anestopoulos, Dimitrios T. Trafalis, Maria V. Deligiorgi, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidi

School of Veterinary and Biomedical Sciences: Faculty Publications

Malignant melanoma is one of the most deadly types of solid cancers, a property mainly attributed to its highly aggressive metastatic form. On the other hand, different classes of isothiocy- anates, a class of phytochemicals, present in cruciferous vegetables have been characterized by considerable anti-cancer activity in both in vitro and in vivo experimental models. In the current study, we investigated the anti-cancer response of five isothiocyanates in an in vitro model of melanoma consisting of non-metastatic (A375, B16F-10) and metastatic (VMM1, Hs294T) malignant melanoma as well as non-melanoma epidermoid carcinoma (A431) and non-tumorigenic melanocyte-neighboring keratinocyte (HaCaT) cells. Our aim …

Il-10 As A Th2 Cytokine: Differences Between Mice And Humans, Mahima T. Rasquinha, Meghna Sur, Ninaad Lasrado, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

The discovery of interleukin (IL)-10 more than 30 years ago marked the beginning of our understanding of how cytokines regulate immune responses, based on cross-regulation between T helper (Th)1 and Th2 cytokines. Although multiple cell types were shown to produce IL-10, its identity as a Th2 cytokine remained strong since it was rigidly associated with Th2 clones in mice, whereas both Th1 and Th2 clones could secrete IL-10 in humans. However, as new Th1/Th2 cell functionalities emerged, anti-inflammatory action of IL-10 gained more attention than its inhibitory effect on Th1 cells, which may occur as an indirect consequence of suppression …

Auxin-Induced Degradation Of Dream Proteins, Lin-9 And Lin-54, In Caenorhabditis Elegans, Karli E. Chosa

Dissertations, Master's Theses and Master's Reports

The Dp, Retinoblastoma, E2F, And MuvB (DREAM) complex mediates transcriptional repression and is highly conserved throughout a number of species, including vertebrates, Drosophila melanogaster, and Caenorhabditis elegans. Differing from mammalian DREAM, C.elegans DRM, appears to act solely in a repressive role, with the MuvB subcomplex (LIN-9, LIN-37, LIN-52, LIN-53, and LIN-54) playing a key role in the repression of genes. In this study, we use the auxin-inducible degron (AID) system, an effective, fast-acting, tool used in the degradation of degron-tagged proteins to individually deplete two key proteins of the MuvB subcomplex, LIN-9 and LIN-54, in C. elegans. The …

Applications Of Machine Learning In Microbial Forensics, Ryan B. Ghannam

Dissertations, Master's Theses and Master's Reports

Microbial ecosystems are complex, with hundreds of members interacting with each other and the environment. The intricate and hidden behaviors underlying these interactions make research questions challenging – but can be better understood through machine learning. However, most machine learning that is used in microbiome work is a black box form of investigation, where accurate predictions can be made, but the inner logic behind what is driving prediction is hidden behind nontransparent layers of complexity.

Accordingly, the goal of this dissertation is to provide an interpretable and in-depth machine learning approach to investigate microbial biogeography and to use micro-organisms as …

Profiling Of Fda-Approved And Clinical Trial Drugs Revealed Shared Cytotoxicity And Collateral Sensitivity In Resistant (H69ar) And Non-Resistant (H69) Small Cell Lung Cancer Cells. (Drug Repurposing In Cancer Chemotherapy), Pius Reyderg Agyemang

Electronic Theses and Dissertations

Some cancers are capable of “spitting out” drugs being fed to them, metaphorically speaking, becoming resistant to what were previously effective chemotherapeutics. In small-cell lung cancer (SCLC), an overexpression of a membrane protein (MRP1) and its transport activity can lead to chemotherapy failure. However, this study showed that certain drugs are selectively cytotoxic (exhibit collateral sensitivity) to MRP1-overexpressed SCLC (H69AR) cells. In this study, three drugs (Erlotinib, Pyrimethamine, Fludarabine) were identified to exhibit a dose-dependent collateral sensitivity on H69AR with IC50 values of ~3.5 μM, ~2 μM, and ~20 μM respectively. Halting the transport activity of the MRP1 with 25 …

Dietary Protein Content And Digestibility Influences Discrimination Of Amino Acid Nitrogen Isotope Values In A Terrestrial Omnivorous Mammal, John P. Whiteman, Mauriel Rodriguez Curras, Kelli L. Feeser, Seth D. Newsome

Biological Sciences Faculty Publications

RATIONALE: Ecologists increasingly determine the δ¹⁵N values of amino acids (AA) in animal tissue; "source" AA typically exhibit minor variation between diet and consumer, while "trophic" AA have increased δ¹⁵N values in consumers. Thus, trophic-source δ¹⁵N offsets (i.e., Δ¹⁵N_T-S) reflect trophic position in a food web. However, even minor variation in δ¹⁵N_{source AA} values may influence the magnitude of offset that represents a trophic step, known as the trophic discrimination factor (i.e., TDF_T-S). Diet digestibility and protein content can influence the δ¹⁵N values …