Biochemistry Commons^™

Positron Emission Tomography In Oncology And Environmental Science, Samantha Delaney

Dissertations, Theses, and Capstone Projects

The last half century has played witness to the onset of molecular imaging for the clinical assessment of physiological targets. While several medical imaging modalities allow for the visualization of the functional and anatomical properties of humans and living systems, few offer accurate quantitation and the ability to detect biochemical processes with low-administered drug mass doses. This limits how physicians and scientists may diagnose and treat medical issues, such as cancer, disease, and foreign agents.

A promising alternative to extant invasive procedures and suboptimal imaging modalities to assess the nature of a biological environment is the use of positron emission …

A Review Of Rheb Activation Of Mtorc1 And The Great Mystery Of One Missing Gef, Jack Gregory

Senior Honors Theses

The mTORC1 pathway is involved in the regulation of cell growth and translation. The pathway has a complex web of activators and inhibitors to activate mTORC1. mTORC1 is regulated via a small GTPase called Rheb, which interacts directly with mTORC1. This GTPase and its GTPase activating protein (GAP), TSC1/2, have been widely studied to understand how the variety of regulators of mTORC1 interact with these proteins. Despite this, the guanine nucleotide exchange factor (GEF) of Rheb has yet to be identified. This review broadly analyzes Rheb and mTORC1, their structures, regulations, and interactions, and explores the mystery of the missing …

A Combination Of Generated Hydrogen Sulfide And Nitric Oxide Activity Has A Potentiated Protectant Effect Against Cisplatin Induced Nephrotoxicity, Faria Khurshid, Javeid Iqbal, Fiaz Ud Din Ahmad, Arslan Hussain Lodhi, Abdul Malik, Suhail Akhtar, Azmat Ali Khan, Marvi Imam Bux, Mohammed Younis

Biomedical Sciences Faculty Publications

Aim: Hydrogen sulfide and nitricoxide possess cytoprotective activity and in vivo, they are generated from exogenous sodium hydrosulfide and L-arginine respectively. Cisplatin is a major chemotherapeutic agent used to treat cancer and has a high incidence of nephrotoxicity as a side effect. The study aim was to explore the effects of NaHS and L-arginine or their combination on cisplatin induced nephrotoxicity in rats. Methods: Wistar Kyoto rats were given a single intraperitoneal dose of cisplatin (5 mg/kg) followed either by NaHS (56 μmol/kg, i. p.), L-arginine (1.25 g/L in drinking water) or their combination daily for 28-days. Post-mortem plasma, urine …

The Purification And Thermal Stability Of The Peroxidase Enzyme In Cucurbita Moschata, Garen Hamner

Senior Honors Theses

Peroxidases are enzymes that catalyze the reduction of hydrogen peroxide to water while oxidizing organic substrates and are valuable in spheres like industrial and medical applications and histochemistry. Limitations still exist in the use of the well-studied horseradish peroxidase for certain activities due to limitations like poor thermal stability, thus the search for novel peroxidases that can overcome these limitations is an active area of research. Butternut squash peroxidase (Cucurbita moschata) (BSP) shows promise due to significant activity being found in the skin and apparent enhanced thermal stability, but an efficient purification scheme for it is lacking, as well as …

Hgs-3 The Influence Of A Tandem Cycling Program In The Community On Physical And Functional Health, Therapeutic Bonds, And Quality Of Life For Individuals And Care Partners Coping With Parkinson’S Disease, Leila Djerdjour, Jennifer L. Trilk

SC Upstate Research Symposium

Purpose Statement: Several studies have shown that aerobic exercise can have a positive impact on alleviating symptoms experienced by individuals with Parkinson's disease (PD). Despite this evidence, the potential benefits of exercise for both PD patients and their care partners (PD dyad) remain unexplored. This research project investigates the effectiveness, therapeutic collaborations, and physical outcomes of a virtual reality (VR) tandem cycling program specifically designed for PD dyads.

Methods: Following approval from the Prisma Health Institutional Review Board, individuals with PD were identified and screened by clinical neurologists. The pre-testing measures for PD dyads (N=9) included emotional and cognitive status …

Using Artificial (Ai) To Predict A Structure Of Protein Complex, Yiqing Zang

SACAD: John Heinrichs Scholarly and Creative Activity Days

Proteins play pivotal roles in essential life processes and elucidating their three-dimensional (3D) structures is crucial for understanding their functions. AlphaFold2, an advanced artificial intelligence-based method developed by Google DeepMind, has emerged as a promising tool for predicting protein structures. In this study, we evaluated the predictive capabilities of AlphaFold2. Our findings highlight AlphaFold2's efficacy in providing valuable insights into protein structure prediction, albeit with certain limitations. While AlphaFold2 represents a significant advancement in the field, its utility is best realized when integrated with complementary experimental approaches. Consequently, combining the strengths of AlphaFold2 with experimental validation remains essential for achieving …

Discovery Of A Small-Molecule Inhibitor That Traps Polθ On Dna And Synergizes With Parp Inhibitors, William Fried, Mrityunjay Tyagi, Leonid Minakhin, Gurushankar Chandramouly, Taylor Tredinnick, Mercy Ramanjulu, William Auerbacher, Marissa L Calbert, Timur Rusanov, Trung Hoang, Nikita Borisonnik, Robert Betsch, John Krais, Yifan Wang, Umeshkumar Vekariya, John Gordon, George Morton, Tatiana Kent, Tomasz Skorski, Neil Johnson, Wayne Childers, Xiaojiang Chen, Richard Pomerantz

Department of Biochemistry and Molecular Biology Faculty Papers

The DNA damage response (DDR) protein DNA Polymerase θ (Polθ) is synthetic lethal with homologous recombination (HR) factors and is therefore a promising drug target in BRCA1/2 mutant cancers. We discover an allosteric Polθ inhibitor (Polθi) class with 4-6 nM IC₅₀ that selectively kills HR-deficient cells and acts synergistically with PARP inhibitors (PARPi) in multiple genetic backgrounds. X-ray crystallography and biochemistry reveal that Polθi selectively inhibits Polθ polymerase (Polθ-pol) in the closed conformation on B-form DNA/DNA via an induced fit mechanism. In contrast, Polθi fails to inhibit Polθ-pol catalytic activity on A-form DNA/RNA in which the enzyme binds in …

The Impact Of Mutations In The Arabidopsis Apetela (Ap3) Gene, Hazel R. Frans, Tara Phelps-Durr

SACAD: John Heinrichs Scholarly and Creative Activity Days

The purpose of this research is to understand the molecular functioning of the Arabidopsis thaliana Apetela (Ap3) gene. We created mutations in two sites of the gene, AP3-3 and AP3-5. These are predicted to change AP3 protein structure, which may result in a mutated flower. Analyzing the effects of new mutations allows an understanding of protein formation both in plants and humans.

Parp2 Promotes Break Induced Replication-Mediated Telomere Fragility In Response To Replication Stress, Daniela Muoio, Natalie Laspata, Rachel L Dannenberg, Caroline Curry, Simone Darkoa-Larbi, Mark Hedglin, Shikhar Uttam, Elise Fouquerel

Department of Biochemistry and Molecular Biology Faculty Papers

PARP2 is a DNA-dependent ADP-ribosyl transferase (ARTs) enzyme with Poly(ADP-ribosyl)ation activity that is triggered by DNA breaks. It plays a role in the Base Excision Repair pathway, where it has overlapping functions with PARP1. However, additional roles for PARP2 have emerged in the response of cells to replication stress. In this study, we demonstrate that PARP2 promotes replication stress-induced telomere fragility and prevents telomere loss following chronic induction of oxidative DNA lesions and BLM helicase depletion. Telomere fragility results from the activity of the break-induced replication pathway (BIR). During this process, PARP2 promotes DNA end resection, strand invasion and BIR-dependent …

A Comparison Of In Vitro Studies Between Cobalt(Iii) And Copper(Ii) Complexes With Thiosemicarbazone Ligands To Treat Triple Negative Breast Cancer, Duaa R. Alajroush, Chloe B. Smith, Brittney F. Anderson, Ifeoluwa T. Oyeyemi, Stephen J. Beebe, Alvin A. Holder

Undergraduate Research Symposium

Triple negative breast cancer (TNBC) is one of the most aggressive forms of breast cancer, and disproportionately affects African American women. TNBC cells lack the common hormone receptors that many pre-existing cancer treatments target. Fortunately, metal-based complexes with thiosemicarbazone ligands have gained significant attention for their potential as anti-cancer agents. Cobalt(III) complex ([Co(phen)2(MeATSC)](NO3)3•1.5H2O•C2H5OH]) and Copper(II) complex ([Cu(acetylethTSC)Cl]Cl•0.25C2H5OH) specifically have properties of high toxicity, which can contribute to decreased cancer cell activity. The effects of these complexes are currently being investigated on cancerous and non-cancerous breast cell lines. The cytotoxic effect of the cobalt(lll) complex and the copper(ll) complex was analyzed …

High Resolution Mass Spectrometry As A Platform For The Analysis Of Polyoxometalates, Their Solution Phase Dynamics, And Their Biological Interactions., Daniel T. Favre

Doctoral Dissertations

Polyoxometalates (POMs) are a class of inorganic molecule of increasing interest to the inorganic, bioinorganic and catalytic communities among many others. While their prevalence in research has increased, tools and methodologies for the analysis of their fundamental characteristics still need further development. Decavanadate (V10) specifically has been postulated to have several unique properties that have not been confirmed independently. Mass spectrometry (MS) and its ability to determine the composition of solution phase species by both mass and charge is uniquely well suited to the analysis of POMs. In this work we utilized high-resolution mass spectrometry to characterize V10 in aqueous …

The Impact Of A Non-Ionic Adjuvant To The Persistence Of Pesticides On Produce Surfaces, Daniel Barnes

Masters Theses

Adjuvants can enhance the performance of the pesticide active ingredients in many ways including decreasing surface tension and reducing evaporation. Understanding how adjuvants effect pesticide behavior (e.g., surface persistence) is crucial for developing effective pesticide formulations, as well as facilitating the development of effective approaches to reduce pesticide residues from the surface of fresh produce post-harvest. The objective of this study is to investigate the effect of a non-ionic surfactant, Surf-Ac 910, on the persistence of two model pesticides, thiabendazole and phosmet on apple surfaces. The result shows that the addition of Surf-Ac 910 increased both the maximum wetted area …

Coomassie Brilliant Blue Dye As A Method For Analyzing Fracture Markings In Bone, Abigail Hoffmeister, David Harutunyan, Matthew Aizawa, Everett Baker, Brandon Mendoza, Chase Freeman, Siran Iskanian

Seaver College Research And Scholarly Achievement Symposium

Coomassie Brilliant Blue Dye is a dye commonly used to stain proteins. Because of its ability to adhere to proteins, this research has focused on perfecting a method of dyeing a fractured flat bone in order to most accurately observe and analyze fracture markings within the trabecular layer. Stereoscopic microscopy was the chosen technique of analysis for this research because of its proven effectiveness in glass and ceramic fractography to observe varying depths. In order to most effectively apply stereoscopic microscopy to this research, the following variables were manipulated to maximize color contrast in the trabecular layer in order to …

Two Dot1 Enzymes Cooperatively Mediate Efficient Ubiquitin-Independent Histone H3 Lysine 76 Tri-Methylation In Kinetoplastids, Victoria Frisbie, Hideharu Hashimoto, Yixuan Xie, Francisca De Luna Vitorino, Josue Baeza, Tam Nguyen, Zhangerjiao Yuan, Janna Kiselar, Benjamin Garcia, Erik Debler

Department of Biochemistry and Molecular Biology Faculty Papers

In higher eukaryotes, a single DOT1 histone H3 lysine 79 (H3K79) methyltransferase processively produces H3K79me2/me3 through histone H2B mono-ubiquitin interaction, while the kinetoplastid Trypanosoma brucei di-methyltransferase DOT1A and tri-methyltransferase DOT1B efficiently methylate the homologous H3K76 without H2B mono-ubiquitination. Based on structural and biochemical analyses of DOT1A, we identify key residues in the methyltransferase motifs VI and X for efficient ubiquitin-independent H3K76 methylation in kinetoplastids. Substitution of a basic to an acidic residue within motif VI (Gx₆K) is essential to stabilize the DOT1A enzyme-substrate complex, while substitution of the motif X sequence VYGE by CAKS renders a rigid active-site …

The Effect Of Ethanol Treatment On The Protein Content Of Difi Exosomes, Kenzie Rushing

Belmont University Research Symposium (BURS)

Colorectal cancer (CRC) is the second most common cause of cancer death in the United States in both men and women combined, second only to lung cancer.1 CRC metastasis is the primary cause of mortality largely due to therapy resistant cancer cells.2 Therefore, detection before metastasis is of great importance and could potentially lead to earlier detection and decreased mortality. Extracellular vesicles (EVs), including exosomes, are lipid bound vesicles secreted by cells3 that are involved in cell-cell communication and have been found to promote CRC progression and metastasis.4 The proteome of exosomes is thought to reflect that of the originating …

Analysis Of Botulinum Toxin A And Interacting Proteins In Skeletal Muscle Cells: An Investigation Into The Mechanisms Of Botulinum Toxin A As A Treatment For Chronic Exertional Compartment Syndrome, Lauren R. Kee

ELAIA

Background Chronic exertional compartment syndrome (CECS) is a condition in which muscle tissue expands against the surrounding fascia during activity and is compressed along with the nerves and blood vessels within the muscle compartment, leading to abnormally high intracompartmental pressure (ICP) and debilitating pain. Treatment typically includes fasciotomy, which results in significant levels of CECS recurrence; however, botulinum toxin A (BoNT-A) injection has recently been seen to decrease both ICP and pain through an unknown mechanism with little to no recurrence. Methods In this study, PyRosetta was used to model the probability of docking interaction between BoNT-A light or heavy …

Evaluation Of Ergosterol And Its Metabolites As Lxr Agonists And Their Anticancer Potential In Colon Cancer, Yogain Taank, Navneet Agnihotri

Research Symposium

Purpose: Aberrant cholesterol homeostasis is a well-recognized hallmark of cancer and implicated in metastasis and chemotherapeutic resistance, the two major causes of cancer associated mortality. Liver X receptors (LXRs) are the key transcription factors that induce cholesterol efflux via enhancing the expression of ABCA1 and ABCG1.

Methods: Molecular docking and dynamic simulation studies were done to assess the binding affinity and stability of the receptor ligand complexes. Activation of LXRs was evaluated using the luciferase reporter assay. qRT-PCR and western blotting was done to analyse the mRNA and protein expression of cholesterol homeostasis genes. Flow cytometric analysis was carried out …

Differentially Disrupted Spinal Cord And Muscle Energy Metabolism In Spinal And Bulbar Muscular Atrophy, Danielle Debartolo, Frederick Arnold, Y Liu, Elana Molotsky, Hsin-Yao Tang, Diane Merry

Department of Biochemistry and Molecular Biology Faculty Papers

Prior studies showed that polyglutamine-expanded androgen receptor (AR) is aberrantly acetylated and that deacetylation of the mutant AR by overexpression of nicotinamide adenine dinucleotide-dependent (NAD+-dependent) sirtuin 1 is protective in cell models of spinal and bulbar muscular atrophy (SBMA). Based on these observations and reduced NAD+ in muscles of SBMA mouse models, we tested the therapeutic potential of NAD+ restoration in vivo by treating postsymptomatic transgenic SBMA mice with the NAD+ precursor nicotinamide riboside (NR). NR supplementation failed to alter disease progression and had no effect on increasing NAD+ or ATP content in muscle, despite producing a modest increase of …

Antioxidant Properties Of Kombucha Beverage Infused With Ganoderma Lucidum And Green Tea From Camellia Sinensis (L.) Kuntze With Several Fermentation Times, Rizki Rabeca Elfirta, Pamungkas Rizki Ferdian, Iwan Saskiawan, Tri Hadi Handayani, Kayla Faza Gustafri Mandalika, Rini Riffiani, Kasirah Kasirah, Ukhradiya Magharaniq Safira Purwanto

Karbala International Journal of Modern Science

Kombucha is a functional beverage produced through the fermentation of infused tea or Camelia sinensis (L.) Kuntze (CS) by a symbiotic culture of bacteria and yeast. Apparently, the substrate of kombucha can be substituted to enhance its functional properties. Ganoderma lucidum (GL) is a potential substrate reported to have health benefits. This study aims to evaluate antioxidant properties by comparing different formulations and fermentation times. The formulations prepared in the present study varied in the compositions of GL and CS substrates, namely F1 (100% GL), F2 (75% GL: 25% CS), F3 (50% GL: 50% CS), F4 (25% GL: 75% CS), …

Raw Nmr Data For Tripeptides, David J. Michaelis, Scott R. Burt, Mariur Rodriguez Moreno, Nye C. Johnson, Christopher B. Stewart, Mary L. Setelin, Adam X. Wayment, Braxton M. Felix

ScholarsArchive Data

This data set contains primary data for 50 tripeptides that were generated as part of an advanced undergraduate laboratory experience in solid phase peptide synthesis. The raw data can be processed sing NMR interpretation software and can be used as problems for exams and quizzes or as supplementary materials for a laboratory experience