Biochemistry, Biophysics, and Structural Biology Commons^™

Restructuring The Gut Microbiota By Intermittent Fasting Lowers Blood Pressure, Huanan Shi, Bojun Zhang, Taylor Abo-Hamzy, James W Nelson, Chandra Shekar R Ambati, Joseph F Petrosino, Robert M Bryan, David J Durgan

Faculty, Staff and Students Publications

Rationale:

In recent years, it has been demonstrated that a pathological change in the gut microbiota, termed gut dysbiosis, can be an underlying factor for the development of hypertension. Prevention of this dysbiosis can attenuate or abolish hypertension. Translational mechanisms to prevent gut dysbiosis as well as understanding of the mechanisms linking gut dysbiosis to hypertension are lacking.

Objective:

We first examined the efficacy of intermittent fasting (IF) in altering the gut microbiota and lowering blood pressure (BP). Next, we utilized a multi-omics approach to examine microbial influenced metabolites that may serve as the link between the gut microbiota and …

Computational Modeling, Energy State Calculations, And Determination Of The Barriers To Rotation Of Atropisomeric Β-Carbolines, Lorenzo Battistoni

Chemistry & Biochemistry Student Scholarship

Major: Biochemistry
Faculty Mentor: Dr. Seann Mulcahy

Axially chiral molecules that have high barriers to rotation about a single bond are called atropisomers. This project aims to expand information on atropisomeric β-carbolines by utilizing computational chemistry to generate energy profiles and determine the barriers to rotation of a library of atropisomeric β-carboline compounds using the program Spartan. Various substituents on the atropisomeric β-carboline scaffold can impact steric strain, electronic effects, and intramolecular hydrogen bonding in the molecule. These factors can impede bond rotation. We will be able to determine which atropisomeric β-carbolines are the best suited to synthesize experimentally using …

An Investigation Of K2 Mycobacteriophage Lysin A Proteins, Ethan Dionne

Chemistry & Biochemistry Student Scholarship

Major: Biochemistry
Faculty Mentor: Dr. Kathleen Cornely, Chemistry and Biochemistry

Investigations Into The Cellular Target Of 4-Trifluoromethoxy Chalcone Via Darts Method, Jordan Stacy

Undergraduate Theses

Cellular drug target discovery is an important step in any drugs journey from bench to bedside. This is true for our lab's molecule of interest, the Chalcone. The Chalcone molecule and its derivatives have been identified as small, plant-derived secondary metabolites that, when interacting with human cancer cell lines, trigger apoptotic pathways leading to varying levels of cell death. One derivative, 4-Trifluoromethoxy Chalcone (4TFM), was identified through screenings as inducing the highest death rate in A549 cancer cells, in conjunction with having the lowest IC50, making it a good candidate to use in searching for the currently unknown cellular target …

Control Of Pre-Replicative Complex During The Division Cycle In Chlamydomonas Reinhardtii, Amy E. Ikui, Noriko Ueki, Kresti Pecani, Frederick R. Cross

Publications and Research

DNA replication is fundamental to all living organisms. In yeast and animals, it is triggered by an assembly of pre-replicative complex including ORC, CDC6 and MCMs. Cyclin Dependent Kinase (CDK) regulates both assembly and firing of the pre-replicative complex. We tested temperature-sensitive mutants blocking Chlamydomonas DNA replication. The mutants were partially or completely defective in DNA replication and did not produce mitotic spindles. After a long G1, wild type Chlamydomonas cells enter a division phase when it undergoes multiple rapid synchronous divisions (‘multiple fission’). Using tagged transgenic strains, we found that MCM4 and MCM6 were localized to the nucleus throughout …

Antibacterial And Antioxidant Potential Of A Novel Plant, Eriodictyon Californicum, And Its Healing Abilities, Allie Richards

Undergraduate Theses

Our body is under constant attack of oxidative stress (OS). OS is a crucial factor in the pathogenesis and progression of various chronic diseases such as diabetics, rheumatoid arthritis, myocardial infarction, cardiovascular diseases, stroke, cancer, Alzheimer’s disease, Parkinson’s disease, aging and more. The main cause of OS is free radicals, which are continuously generated in our body during normal metabolic processes. These free radicals have the potential to damage any of our key biomolecules. To protect ourselves from the toxic effect of free radicals the human body has a built-in army of antioxidants that play an important role in the …

Effects Of Curcumin And Its Different Formulations In Preclinical And Clinical Studies Of Peripheral Neuropathic And Postoperative Pain: A Comprehensive Review, Paramita Basu, Camelia Maier, Arpita Basu

Kinesiology and Nutrition Sciences Faculty Research

Lesion or disease of the somatosensory system leads to the development of neuropathic pain. Peripheral neuropathic pain encompasses damage or injury of the peripheral nervous system. On the other hand, 10–15% of individuals suffer from acute postoperative pain followed by persistent pain after undergoing surgeries. Antidepressants, anticonvulsants, baclofen, and clonidine are used to treat peripheral neuropathy, whereas opioids are used to treat postoperative pain. The negative effects associated with these drugs emphasize the search for alternative therapeutics with better efficacy and fewer side effects. Curcumin, a polyphenol isolated from the roots of Curcuma longa, possesses antibacterial, antioxidant, and anti-inflammatory properties. …

Europium Sulfide Nanoprobes Predict Antiretroviral Drug Delivery Into Hiv-1 Cell And Tissue Reservoirs, Jonathan Herskovitz, Mahmudul Hasan, Jatin Machhi, Insiya Mukadam, Brendan M. Ottemann, James R. Hilaire, Christopher Woldstad, Joellyn Mcmillan, Yutong Liu, Javier Seravalli, Anandakumar Sarella, Howard E. Gendelman, Bhavesh D. Kevadiya

Department of Biochemistry: Faculty Publications

Background: Delivery of long-acting nanoformulated antiretroviral drugs (ARVs) to human immunodeficiency virus type one cell and tissue reservoirs underlies next generation antiretroviral therapeutics. Nanotheranostics, comprised of trackable nanoparticle adjuncts, can facilitate ARV delivery through real-time drug tracking made possible through bioimaging platforms. Methods: To model HIV-1 therapeutic delivery, europium sulfide (EuS) nanoprobes were developed, characterized and then deployed to cells, tissues, and rodents. Tests were performed with nanoformulated rilpivirine (NRPV), a non-nucleoside reverse transcriptase inhibitor (NNRTI) used clinically to suppress or prevent HIV-1 infection. First, CD4+ T cells and monocyte-derived macrophages were EuS-treated with and without endocytic blockers to identify …

The Analysis Of Folate-Dependent Transcription Factor Zinc Finger Protein 410, Feifan Xu

Senior Honors Theses

A previous study that introduced dietary folate to mice in the form of folic acid to determine if gene activity would be altered based on this biological molecule demonstrated that mice without folic acid had cognition deficits, and this phenomenon was correlated with altered gene expression in their brains. The included bioinformatic analysis revealed two main transcription factors that bind to proteins in the nucleus, and one is known as the Zinc Finger Protein 410 (Zfp410). Due to the lack of literature explaining the function of this transcription factor, this project is intended to analyze Zfp410 in detail from scratch. …

216— Loss Of Function Mutation For Tp53 Does Not Rescue The Chaf1bNt2 Small-Eye Phenotype In Danio Rerio, Alex Parks

GREAT Day Posters

In Zebrafish, the chromosome assembly factor 1b (chaf1b) gene is in part responsible for the development of the eye. In homozygous chaf1bt24412 mutants retinal cell death is promoted through cell-death promoting activity of the gene, tumor suppressor protein p53 (tp53), resulting in a small-eye phenotype. Another allele chaf1bnt2, was found to also result in the small-eye phenotype when in a homozygous state. We found that knockdown of Tp53 protein via morpholino antisense oligonucleotide injection of 1-2 cell stage embryos failed to rescue retinal cell death of chaf1bnt2 homozygous mutants as detected by TUNEL labeling. Because morpholinos may fail to fully …

A High-Androgen Microenvironment Inhibits Granulosa Cell Proliferation And Alters Cell Identity, Renee M. Mcfee, Sarah M. Romereim, Alexandria P. Snider, Adam F. Summers, William E. Pohlmeier, Scott G. Kurz, Robert A. Cushman, John S. Davis, Jennifer R. Wood, Andrea S. Cupp

School of Veterinary and Biomedical Sciences: Faculty Publications

A naturally occurring bovine model with excess follicular fluid androstenedione (High A4), reduced fertility, and polycystic ovary syndrome (PCOS)-like characteristics has been identified. We hypothesized High A4 granulosa cells (GCs) would exhibit altered cell proliferation and/or steroidogenesis. Microarrays of Control and High A4 GCs combined with Ingenuity Pathway Analysis indicated that High A4 GCs had cell cycle inhibition and increased expression of microRNAs that inhibit cell cycle genes. Granulosa cell culture confirmed that A4 treatment decreased GC proliferation, increased anti-Müllerian hormone, and increased mRNA for CTNNBIP1. Increased CTNNBIP1 prevents CTNNB1 from interacting with members of the WNT signaling pathway thereby …

Using The Lambert Function To Map Enzyme Kinetics, Melissa Gouge

ONU Student Research Colloquium

In an academic setting, enzyme kinetics are introduced by analysis of the initial rates using the Michalis-Menten model. To better understand enzyme kinetics, a complete time course analysis will provide a larger set of information. The use of the integrated form of the rate equation allows for a beginning glance at the mechanism of reaction. With this, the Lambert Ω function can be used to analyze the integrated rate equations. There are two different branches of the Lambert Ω function, a negative branch and a positive branch. For each branch there is a unique expanded series approximation used for analysis …

The Effect Of Cadmium On Ovarian Adenocarcinoma Cell Lines: An Investigation Of The Possible Mechanism Of Action, Haley Todd

Undergraduate Theses

Cadmium, a heavy metal and carcinogen, is an environmental and workplace contaminate. As a known endocrine disruptor, it can mimic the proliferative effects of estrogen and is classified as a metalloestrogen. While the proliferative effect of estrogen on cancerous cell growth has been well established, the effects of cadmium have not been fully examined. To determine if cadmium stimulates growth in two human ovarian adenocarcinoma cell lines, OVCAR3 and SKOV3, cells were treated for 48 hours with varying concentrations of cadmium, 0.001 µM – 10 µM, and growth was measured using a cell proliferation assay. Both cell lines showed a …

Vitamin D3 Induces Mesenchymal-To-Endothelial Transition And Promotes A Proangiogenic Niche Through Igf-1 Signaling, Lei Chen, Anweshan Samanta, Lin Zhao, Nathaniel R. Dudley, Tanner Buehler, Robert J. Vincent, Jeryl Hauptman, Magdy Girgis, Buddhadeb Dawn

School of Medicine Faculty Research

Biological Sciences; Physiology; Molecular Biology; Cell Biology

Crispr/Cas9-Induced Fad2 And Rod1 Mutations Stacked With Fae1 Confer High Oleic Acid Seed Oil In Pennycress (Thlaspi Arvense L.), Brice A. Jarvis, Trevor B. Romsdahl, Michaela G. Mcginn, Tara J. Nazarenus, Edgar B. Cahoon, Kent D. Chapman, John C. Sedbrook

Department of Biochemistry: Faculty Publications

Pennycress (Thlaspi arvense L.) is being domesticated as an oilseed cash cover crop to be grown in the off-season throughout temperate regions of the world. With its diploid genome and ease of directed mutagenesis using molecular approaches, pennycress seed oil composition can be rapidly tailored for a plethora of food, feed, oleochemical and fuel uses. Here, we utilized Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 technology to produce knockout mutations in the FATTY ACID DESATURASE2 (FAD2) and REDUCED OLEATE DESATURATION1 (ROD1) genes to increase oleic acid content. High oleic acid (18:1) oil is valued for its oxidative stability that is …

Tocilizumab In Hospitalized Patients With Severe Covid-19 Pneumonia, Ivan O Rosas, Norbert Bräu, Michael Waters, Ronaldo C Go, Bradley D Hunter, Sanjay Bhagani, Daniel Skiest, Mariam S Aziz, Nichola Cooper, Ivor S Douglas, Sinisa Savic, Taryn Youngstein, Lorenzo Del Sorbo, Antonio Cubillo Gracian, David J De La Zerda, Andrew Ustianowski, Min Bao, Sophie Dimonaco, Emily Graham, Balpreet Matharu, Helen Spotswood, Larry Tsai, Atul Malhotra

Faculty, Staff and Students Publications

BACKGROUND: Coronavirus disease 2019 (Covid-19) is associated with immune dysregulation and hyperinflammation, including elevated interleukin-6 levels. The use of tocilizumab, a monoclonal antibody against the interleukin-6 receptor, has resulted in better outcomes in patients with severe Covid-19 pneumonia in case reports and retrospective observational cohort studies. Data are needed from randomized, placebo-controlled trials.

METHODS: In this phase 3 trial, we randomly assigned patients who were hospitalized with severe Covid-19 pneumonia in a 2:1 ratio receive a single intravenous infusion of tocilizumab (at a dose of 8 mg per kilogram of body weight) or placebo. Approximately one quarter of the participants …

The Context-Dependent Impact Of Integrin-Associated Cd151 And Other Tetraspanins On Cancer Development And Progression: A Class Of Versatile Mediators Of Cellular Function And Signaling, Tumorigenesis And Metastasis, Sonia F. Erfani, Hui Hua, Yueyin Pan, Binhua P. Zhou, Xiuwei H. Yang

Molecular and Cellular Biochemistry Faculty Publications

As a family of integral membrane proteins, tetraspanins have been functionally linked to a wide spectrum of human cancers, ranging from breast, colon, lung, ovarian, prostate, and skin carcinomas to glioblastoma. CD151 is one such prominent member of the tetraspanin family recently suggested to mediate tumor development, growth, and progression in oncogenic context- and cell lineage-dependent manners. In the current review, we summarize recent advances in mechanistic understanding of the function and signaling of integrin-associated CD151 and other tetraspanins in multiple cancer types. We also highlight emerging genetic and epigenetic evidence on the intrinsic links between tetraspanins, the epithelial-mesenchymal transition …

Funtionalization Of Morphologically Different Nanoclays For Enhanced Mechanical Properties, Malachi Kent

Honors College Theses

Nanoclays are microscopic clays that are comprised of layered nanoparticle aluminosilicates that are naturally arranged in several morphologies. Halloysite nanotubes (HNT) are hollow, double-layered tubes, bentonite (BNT) clays are trapezoidal platelets, and nanosilica or silica dioxide (SiO₂) are spherical. These nanoclays were chosen for sustainable purposes as they are naturally derived and for economical purposes because of their cheap commercial availability. In this study, the nanoclays are functionalized with an epoxy organosilane group through reflux conditions at 120 °C for 24 hours. The pristine and functionalized nanoclays were extensively characterized with infrared radiation (IR) spectroscopy, scanning electron microscope …

Studies Of The Rectification Behavior Of The Pdt Ligand And The Active Site Of Msrp, Laura J. Ingersol

Chemistry and Chemical Biology ETDs

Molybdenum (Mo) is an essential element that plays an important role in global nitrogen, carbon, and sulfur cycles with a critical role in human metabolism and ecological balance. It becomes catalytically active when complexed with the pyranopterin dithiolene ligand (PDT), forming the nearly ubiquitous molybdenum cofactor (Moco). The complex biosynthetic pathway of Moco, its presence in all three domains of life, and its role as a constituent cofactor in the last universal common ancestor (LUCA) all point toward the importance of the PDT in the development of life on Earth. Molybdoenzymes catalyze the two-electron oxidation or reduction of substrates that …

Project Alien, Rebecca Mccallin, Madelyn Hoying, Alex Evans, Matthew Nestler, Karli Rae Sutton, Garett Craig, Lucia Secaia Del Cid, Alexander Guy, Rachel Fernandez, Amanda Trusiak, Paige Aley, Ingabire Gakwerere, Nina Dorfner, Maria Mosbacher, Mary Flavin, Selvin Hernandez, Audrey Steen, Benjamin Kazimer

Undergraduate Research and Scholarship Symposium

Project ALIEN is a comprehensive plan to send humans to Mars to look for life on the Martian surface while exploring the viability and adaptability of terrestrial microbes in Martian atmospheric conditions. ALIEN will use a ballistic capture trajectory to get to Mars and stay in aerostationary orbit for a 30-day surface mission, during which two surface crewmembers will perform a variety of experiments to achieve the mission’s goals of Martian microbial discovery within brines of the Gale Crater and terrestrial microbe adaptability and viability to Martian conditions. Experimentation is based on the presumption that Martian microbes are metabolically similar …