Biochemistry, Biophysics, and Structural Biology Commons^™

Effects Of Post-Translational Histone Modifications On Transcription Rate, Jacob Hunter, Steven Johnson, Aaron Bohn, Sarah Ricks, Sarah Hodson, David Bates, Steven M. Johnson

Library/Life Sciences Undergraduate Poster Competition 2024

DNA structure and organization in eukaryotic cells significantly impacts the regulation of geneexpression, cellular properties and overall behavior. At the most fundamental unit of this organization,~147 bp of DNA wraps 1.7 times around a histone octamer core, forming a collective unit called thenucleosome. Positioning and occupancy of nucleosomes around promoter elements of genes is knownto be a strong regulator of transcription in eukaryotic nuclei. Post-translational modifications (PTM’s) tothe protruding N-terminal tails of histone proteins are known to influence chromatin structure and thusgene expression; however, relatively little is known about the residual effect of histone PTM’s ontranscription rate.

Design To Data For Mutants Of Β-Glucosidase B From Paenibacillus Polymyxa: E26k, I170y, And V398n, Carter Ahlstedt, Annika Bennett, Daniel Kaluka

Lux et Fides: A Journal for Undergraduate Christian Scholars

Protein modeling aids in developing novel protein configurations that are critical in, for example, the pharmaceutical and environmental industries. However, the predictive capabilities of the protein modeling algorithms are limited due to a lack of experimental data on structure and function. To bridge this gap, Seigel Lab at UC Davis developed the Design to Data (D2D) program to catalog thermal stability and catalytic efficiency data sets on β-glucosidase B (BglB) variants. Over 300 BglB variants have been characterized. However, there are over 8400 possible BglB single-point mutations. We utilized Foldit software to design BglB mutants E26K, I170Y, and V398N. The …

Effects Of Diminazene Aceturate On Drosophila Melanogaster: A Lipidomic Analysis, Gabriela Suarez

USF Tampa Graduate Theses and Dissertations

Pesticides are agents designed to eradicate living organisms to preserve agricultural needs.¹ Today the most commonly used pesticides are termed “modern pesticides”, they are characterized by lower lipophilicity and limited stability, making them less time persistent in the environment. Among these modern pesticides are organophosphorus, urea, phenoxy alkanoic, triazine, chloroacetanilide, and glyphosate-based pesticides.² The issue faced with most of these pesticides is that they affect more than just the targeted pest and pose a danger to not only humans, but also entire ecosystems.^1,3,4 While there are many different types of pesticides, insecticides show the most variance and …

Design Of The Strive-Ipf Trial- Study Of Therapeutic Plasma Exchange, Rituximab, And Intravenous Immunoglobulin For Acute Exacerbations Of Idiopathic Pulmonary Fibrosis, Tejaswini Kulkarni, Gerard J Criner, Daniel J Kass, Ivan O Rosas, Mary Beth Scholand, Daniel F Dilling, Ross Summer, Steven R Duncan

Faculty, Staff and Students Publications

BACKGROUND: Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) affect a significant proportion of patients with IPF. There are limited data to inform therapeutic strategies for AE-IPF, despite its high mortality. We discuss the rationale and design of STRIVE-IPF, a randomized, multi-center, open-label Phase IIb clinical trial to determine the efficacy of combined therapeutic plasma exchange (TPE), rituximab, and intravenous immunoglobulin (IVIG), in comparison to treatment as usual (TAU), among patients with acute IPF exacerbations.

METHODS: The STRIVE-IPF trial will randomize 51 patients among five sites in the United States. The inclusion criteria have been designed to select a study population …

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 …

Remodeling Anaplastic Thyroid Cancer's Aggressive Profile And Metabolic Signature By Natural Alkaloid Berberine, Tara Elizabeth Jarboe

NYMC Student Theses and Dissertations

Anaplastic thyroid cancer is a rare, fatal cancer with a five-year survival of 4%. Universally diagnosed at stage IV, anaplastic thyroid cancer is characterized by its lack of differentiation, rapid proliferative rate, highly inflammatory tumor microenvironment, and metabolic dysregulation. Refractory to all established therapies, anaplastic thyroid cancer requires a novel therapeutic approach that targets all of these drivers of anaplastic thyroid cancer carcinogenesis. We propose natural alkaloid berberine as a therapeutic with multitarget efficacy to alter mitochondrial metabolism and reprogram anaplastic thyroid cancer’s aggressive phenotype. Our in vitro model uses monocyte cell line U937, anaplastic thyroid cancer cell lines T238 …

The Polyglutamine Domain Is The Primary Driver Of Seeding In Huntingtin Aggregation, Adam Skeens, Chathuranga Siriwardhana, Sophia E. Massinople, Michelle M. Wunder, Zachary L. Ellis, Kaitlyn M. Keith, Tyler Girman, Shelli L. Frey, Justin Legleiter

Chemistry Faculty Publications

Huntington’s Disease (HD) is a fatal, neurodegenerative disease caused by aggregation of the huntingtin protein (htt) with an expanded polyglutamine (polyQ) domain into amyloid fibrils. Htt aggregation is modified by flanking sequences surrounding the polyQ domain as well as the binding of htt to lipid membranes. Upon fibrillization, htt fibrils are able to template the aggregation of monomers into fibrils in a phenomenon known as seeding, and this process appears to play a critical role in cell-to-cell spread of HD. Here, exposure of C. elegans expressing a nonpathogenic N-terminal htt fragment (15-repeat glutamine residues) to preformed htt-exon1 fibrils induced …

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

[Archive] 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 …

Identification Of A Novel Target For Declustering Supernumerary Centrosomes In Triple Negative Breast Cancer, Priyanga J

Theses and Dissertations

Triple-negative breast cancer (TNBC) confers considerable interventional challenge owing to its massive heterogeneity, aggression and metastatic prowess. These facets are attributed to chromosomal instability (CIN), a feature consequent to TNBC cell’s ability to harbor more than two centrosomes (supernumerary centrosomes; SNCs).

In principle, if a normal cell possesses SNCs, uneven pull forces are generated consequent to multipolar spindle, which activates cellular surveillance. This ensures error-free mitosis by either repairing the error or, in an irreparable condition, driving cells to death. This averts the possibility of aneuploidy (fundamental to tumorigenesis).

Unfortunately, TNBC cells, despite harboring SNCs, have devised a survival strategy …

Preliminary Investigation Of Differences In Host Mitochondria Membrane Potential During Toxoplasma Gondii Infection, Bryan L. Ortega

USF Tampa Graduate Theses and Dissertations

Toxoplasma gondii is an obligate intracellular protozoan with a broad host range of hosts, including various warm-blooded mammals, including humans. While infections can often be asymptomatic in immunocompetent individuals, they can pose significant risks to those who are immunocompromised, as well as pregnant women. Toxoplasmosis represents a significant burden on public health in the United States, with over 800,000 annual infections reported, often leading to severe complications such as symptomatic eye disease and congenital infections. Recent attention has developed regarding its potential association with human neuropathies such as Alzheimer's disease, dementia, and mood disorders. This project investigated differences in host …

Identification Of Novel Small Molecule Inhibitors Of Twin Arginine Translocation (Tat) Pathway And Their Effect On The Control Of Campylobacter Jejuni In Chickens, Loïc Deblais, Mary Drozd, Anand Kumar, Janet Antwi, James Fuchs, Rahul Khupse, Yosra A. Helmy, Gireesh Rajashekara

School of Veterinary and Biomedical Sciences: Faculty Publications

Introduction: Control of Campylobacter from farm to fork is challenging due to the frequent emergence of antimicrobial-resistant isolates. Furthermore, poultry production systems are known reservoirs of Campylobacter. The twinarginine translocation (Tat) pathway is a crucial bacterial secretion system that allows Campylobacter to colonize the host intestinal tract by using formate as the main source of energy. However, Tat pathway is also a major contributing factor for resistance to copper sulfate (CuSO₄).

Methods: Since mammals and chickens do not have proteins or receptors that are homologous to bacterial Tat proteins, identification of small molecule (SM) inhibitors …

Metatranscriptomic Insights Into The Interaction Between Microcystis Blooms And Hydrogen Peroxide, Taylor L. Hancock

USF Tampa Graduate Theses and Dissertations

For this dissertation I studied the interactions of hydrogen peroxide and cyanobacterial harmful algal blooms (cHABs) dominated by Microcystis in the Caloosahatchee River, FL. Specifically, I examined how taxonomic and functional succession relates to both natural hydrogen peroxide dynamics and hydrogen peroxide added to the environment as a cHAB treatment. Chapter 2 investigated how taxonomic succession and gene expression patterns relate to blooms and associated elevated hydrogen peroxide concentrations. The results showed that gene expressions related to cyanobacterial growth were positively correlated with hydrogen peroxide. The genes identified included enzymes capable of hydrogen peroxide generation which were expressed by blooming …

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 …

Kidney Function Trajectories And Right Heart Failure Following Lvad Implantation, Carl P Walther, Andrew B Civitello, Harveen K Lamba, Nandan K Mondal, Sankar D Navaneethan

Faculty, Staff and Students Publications

BACKGROUND: Preoperative kidney dysfunction is a risk factor for right heart failure (RHF) after implantation of a left ventricular assist device (LVAD). However, characteristic kidney function trajectories before and after post-LVAD RHF are uncertain, so we investigated this.

METHODS AND RESULTS: We identified individuals who received primary continuous-flow LVAD implantation from July 1, 2014 to December 31, 2017 in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) data set. Incident RHF was ascertained using the INTERMACS definition at 1 and 3 months and classified as transient or persistent. Kidney function trajectories before and after RHF onset, and relationships of …

A Potential Role Of Urinary P75ecd As A Biomarker For Amyotrophic Lateral Sclerosis In An American Cohort, Swati Dhasmana, Anupam Dhasmana, Sheema Khan, Acharan S. Narula, Murali Yallapu, Subhash Chauhan

Research Symposium

Background: Neurological disorders present a unique complexity compared to other diseases, involving multiple risk factors, causes, treatments, and outcomes. These disorders often exhibit various molecular and morphological changes indicative of disruptions in cellular plasticity and resilience. The pathogenesis of many neurological disorders remains unclear, necessitating ongoing investigations. Amyotrophic lateral sclerosis (ALS) exemplifies an idiopathic and fatal neurodegenerative disease marked by the degeneration of upper and lower motor neurons. The average life expectancy post-diagnosis is a mere 36 months, primarily attributed to respiratory muscle denervation.The persistent challenges in ALS clinical trials and the absence of effective therapeutic options have intensified interest …

Development Of An Integrated Workflow For Nucleosome Modeling And Simulations, Ran Sun

Doctoral Dissertations

Nucleosomes are the building blocks of eukaryotic genomes and thus fundamental to to all genetic processes. Any protein or drug that binds DNA must either cooperate or compete with nucleosomes. Given that a nucleosome contains 147 base pairs of DNA, there are approximately 4^147 or 10^88 possible sequences for a single nucleosome. Exhaustive studies are not possible. However, genome wide association studies can identify individual nucleosomes of interest to a specific mechanism, and today's supercomputers enable comparative simulation studies of 10s to 100s of nucleosomes. The goal of this thesis is to develop and present and end-to-end workflow that serves …

Structure-Based Targeting Of The Nemo:Ikk Interaction For Canonical Nf-Κb Inhibition, Amy Kennedy

Dartmouth College Ph.D Dissertations

The NF-κB pathway is important for cell survival and proliferation, inflammation, and innate immunity, and its dysregulation is a common theme in many cancers, autoimmune disorders, and other disease states. The protein-protein interaction between the scaffolding protein NEMO and the kinase IKK in the NF-κB pathway represents a compelling target for selective NF-κB inhibition because it occurs only in the canonical branch of the NF-κB pathway. Disruption of the NEMO:IKK interaction has been established for decades in the literature as a safe and effective way to selectively inhibit overactivation of the canonical branch of the NF-κB pathway. The benchmark in …

Ellagic Acid Inhibits Α-Synuclein Propagation And Alleviates The Neurotoxicity By Enhancing Autophagic Flux In Animal Model Of Parkinson’S Disease, Nada Akram Abdellatif

Theses

Parkinson’s Disease (PD) is the second most common neurological disorder pathologically characterized by loss of dopaminergic neurons in the Substantia Nigra pars compacta (SNc) as well as the formation of Lewy bodies composed mainly of α-synuclein (α-syn) aggregates. It has been documented that abnormal aggregation of α-syn is one of the major causes of developing PD. Ellagic Acid (EA) is a widely known dietary supplement found in pomegranates as well as a plethora of berries and nuts. EA has been shown to prevent α-syn aggregates’ toxicity in cellular model of PD. In the current study we aim to evaluate whether …

Dna-Pkcs Rnaseq Data: Dna-Pkcs Wilde-Type Or Kinase-Dead Protein Regulate Basal And Etoposide-Induced Gene Expression Changes, Amanda Ashley

Chemistry & Biochemistry: Datasets

No abstract provided.