Biochemistry, Biophysics, and Structural Biology Commons^™

Anti-Colon Cancer Effect Of Origanum Majorana Essential Oil, Asma Nasser Rashed Alrashedi

Biology Theses

Plants have been shown to be an excellent source of new drugs, including anticancer agents. Origanum majorana commonly known as marjoram is a plant that is known to possess different therapeutic values including antioxidant andantimicrobial activities.

Our research team has previously tested the ethanolic extract of O. majorana on triple negative breast cancer and published the findings. The ethanolic extract promoted mitotic arrest at G2/M phase, induced apoptosis as well as inhibition of migration and metastasis. The promising potential of the ethanolic extract encouraged us to test the effects of O. majorana essential oil on human colon cancer cell lines. …

Toxicological Assessment Of Nanomaterials: The Role Of In Vitro Raman Microspectroscopic Analysis, Esen Efeoglu, Marcus Maher, Alan Casey, Hugh Byrne

Articles

The acceleration of nanomaterials research has brought about increased demands for rapid analysis of their bioactivity, in a multi-parametric fashion, to minimise the gap between potential applications and knowledge of their toxicological properties. The potential of Raman microspectroscopy for the analysis of biological systems with the aid of multivariate analysis techniques has been demonstrated. In this study, an overview of recent efforts towards establishing a ‘label-free high content nanotoxicological assessment technique’ using Raman microspectroscopy is presented. The current state of the art for cellular toxicity assessment and the potential of Raman microspectroscopy are discussed, and the spectral markers of the …

Role Of The Snf2 Homolog, Irc20, In Yeast Genome Maintenance, Deena Mohamed Galal Eldin Ahmed

Theses

In eukaryotes, DNA is wrapped around histone proteins forming a highly compact structure, the chromatin. All DNA-based processes must occur within the complex organization of the chromatin, and this requires modulation of its structure when needed. This is accomplished by covalent histone modifications that alter histone-DNA contacts, as well as through the actions of ATP-dependent chromatin remodelers. These multi-subunit complexes play major roles in transcription regulation, replication and repairing DNA damage. This thesis aims to characterize a poorly studied member of the SWI/SNF family of ATPases/helicases, Irc20, from Saccharomyces cerevisiae. Previously, Irc20 has been shown to be involved in …

Prediction Of Lncrna-Disease Associations Based On Inductive Matrix Completion, Chengqian Lu, Mengyun Yang, Feng Luo, Fang-Xiang Wu, Min Li, Yi Pan, Yaohang Li, Jianxin Wang

Computer Science Faculty Publications

Motivation: Accumulating evidences indicate that long non-coding RNAs (lncRNAs) play pivotal roles in various biological processes. Mutations and dysregulations of lncRNAs are implicated in miscellaneous human diseases. Predicting lncRNA–disease associations is beneficial to disease diagnosis as well as treatment. Although many computational methods have been developed, precisely identifying lncRNA–disease associations, especially for novel lncRNAs, remains challenging.

Results: In this study, we propose a method (named SIMCLDA) for predicting potential lncRNA– disease associations based on inductive matrix completion. We compute Gaussian interaction profile kernel of lncRNAs from known lncRNA–disease interactions and functional similarity of diseases based on disease–gene and gene–gene onotology …

Tracing Actin Filament Bundles In Three-Dimensional Electron Tomography Density Maps Of Hair Cell Stereocilia, Salim Sazzed, Junha Song, Julio Kovacs, Willi Wriggers, Manfred Auer, Jing He

Computer Science Faculty Publications

Cryo-electron tomography (cryo-ET) is a powerful method of visualizing the three-dimensional organization of supramolecular complexes, such as the cytoskeleton, in their native cell and tissue contexts. Due to its minimal electron dose and reconstruction artifacts arising from the missing wedge during data collection, cryo-ET typically results in noisy density maps that display anisotropic XY versus Z resolution. Molecular crowding further exacerbates the challenge of automatically detecting supramolecular complexes, such as the actin bundle in hair cell stereocilia. Stereocilia are pivotal to the mechanoelectrical transduction process in inner ear sensory epithelial hair cells. Given the complexity and dense arrangement of actin …

Mxin Differentially Regulates Monomeric And Oligomeric Species Of The Shigella Type Three Secretion System Atpase Spa47, Heather B. Case, Nicholas E. Dickenson

Chemistry and Biochemistry Faculty Publications

Shigella rely entirely on the action of a single type three secretion system (T3SS) to support cellular invasion of colonic epithelial cells and to circumvent host immune responses. The ATPase Spa47 resides at the base of the Shigella needle-like type three secretion apparatus (T3SA), supporting protein secretion through the apparatus and providing a likely means for native virulence regulation by Shigella and a much needed target for non-antibiotic therapeutics to treat Shigella infections. Here, we show that MxiN is a differential regulator of Spa47 and that its regulatory impact is determined by the oligomeric state of the Spa47 ATPase, with …

Progress Toward Synthetically Simplified Natural Anticancer Peptide, David W. Kastner, Steven L. Castle

Library/Life Sciences Undergraduate Poster Competition 2018

Yaku’amide A was isolated in late 2010 from the deep-sea sponge Ceratopsion sp. and exhibits potent inhibitory activity against 39 human cancer cell lines via a potentially novel mode of action. However, the total synthesis requires many steps and produces low yields. In this study, we determined two simpler YA analogues that may retain its anticancer properties and can be synthesized in larger quantities. The analogues replace dehydroisoleucine with either dehydroethylnorvaline or dehydrovaline.

Cold Atmospheric Plasma Induces Atp-Dependent Endocytosis Of Nanoparticles And Synergistic U373mg Cancer Cell Death, Zhonglei He, Kangze Liu, Eline Manaloto, Alan Casey, George P. Cribaro, Hugh Byrne, Furong Tian, Carlos Barcia, Gillian Conway, Patrick J. Cullen, James Curtin

Articles

Gold nanoparticles (AuNP) have potential as both diagnostic and therapeutic vehicles. However, selective targeting and uptake in cancer cells remains challenging. Cold atmospheric plasma (CAP) can be combined with AuNP to achieve synergistic anti-cancer cytotoxicity. To explore synergistic mechanisms, we demonstrate both rate of AuNP uptake and total amount accumulated in U373MG Glioblastoma multiforme (GBM) cells are signifcantly increased when exposed to 75kV CAP generated by dielectric barrier discharge. No signifcant changes in the physical parameters of AuNP were caused by CAP but active transport mechanisms were stimulated in cells. Unlike many other biological efects of CAP, long-lived reactive species …

Structural Determinants For The Interactions Of Chemically Modified Nucleic Acids With The Stabilin‑2 Clearance Receptor, Hans Gaus, Colton M. Miller, Punit P. Seth, Edward N. Harris

Department of Biochemistry: Faculty Publications

The Stabilin receptors are systemic clearance receptors for some classes of chemically modified nucleic acid therapeutics. In this study, the recombinant human secreted ecto-domain of the small isoform of Stabilin-2 (s190) was purified from cell culture and evaluated for direct binding with a multitude of antisense oligonucleotides (ASOs) using a fluorescence polarizationbased assay. The tested ASOs varied in their backbone composition, modification of the ribose 2′ position, overall length of the oligo, and sequence of the nucleotide bases. A fully phosphorothioate (PS) ASO with a 5−10−5 pattern of flanking 2′-O-methoxyethyl modifications was then used to test the effects …

Self-Oligomerization Regulates Stability Of Survival Motor Neuron Protein Isoforms By Sequestering An ScfSlmb Degron, Kelsey M. Gray, Kevin A. Kaifer, David Baillat, Ying Wen, Thomas R. Bonacci, Allison D. Ebert, Amanda C. Raimer, Ashlyn M. Spring, Sara Ten Have, Jacqueline J. Glascock, Kushol Gupta, Gregory D. Van Duyne, Michael J. Emanuele, Angus I. Lamond, Eric J. Wagner, Christian L. Lorson, A. Gregory Matera

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Spinal muscular atrophy (SMA) is caused by homozygous mutations in human SMN1. Expression of a duplicate gene (SMN2) primarily results in skipping of exon 7 and production of an unstable protein isoform, SMNΔ7. Although SMN2 exon skipping is the principal contributor to SMA severity, mechanisms governing stability of survival motor neuron (SMN) isoforms are poorly understood. We used a Drosophila model system and label-free proteomics to identify the SCF^Slmb ubiquitin E3 ligase complex as a novel SMN binding partner. SCF^Slmb interacts with a phosphor degron embedded within the human and fruitfly SMN YG-box oligomerization domains. …

Increased Liver Tumor Formation In Neutral Sphingomyelinase-2-Deficient Mice, Liansheng Zhong, Ji Na Kong, Michael B. Dinkins, Silvia Leanhart, Zhihui Zhu, Stefka D. Spassieva, Haiyan Qin, Hsuan-Pei Lin, Ahmed Elsherbini, Rebecca Wang, Xue Jiang, Mariana N. Nikolova‑Karakashian, Guanghu Wang, Erhard Bieberich

Physiology Faculty Publications

Sphingolipids are key signaling lipids in cancer. Genome-wide studies have identified neutral SMase-2 (nSMase2), an enzyme generating ceramide from SM, as a potential repressor for hepatocellular carcinoma. However, little is known about the sphingolipids regulated by nSMase2 and their roles in liver tumor development. We discovered growth of spontaneous liver tumors in 27.3% (9 of 33) of aged male nSMase2-deficient (fro/fro) mice. Lipidomics analysis showed a marked increase of SM in the tumor. Unexpectedly, tumor tissues presented with more than a 7-fold increase of C₁₆-ceramide, concurrent with upregulation of ceramide synthase 5. The fro/fro liver tumor, …

Insights Into The Cellular Trafficking Of Perilipin 5, Hannah M. Bailey

Undergraduate Honors Thesis Projects

Perilipins are a family of five proteins found on the surface of lipid storage droplets in nearly all tissues. These proteins act as cofactors for lipases and scaffolding for other proteins involved in lipid metabolism. In addition to the lipid droplet surface, members of the perilipin family have been found in the cytosol, endoplasmic reticulum, plasma membrane and mitochondria. The localization of these proteins is in part due to the phosphorylation state of the perilipin in question. Many other biological processes occur through kinase pathways, which have numerous cellular outcomes. Recently, perilipin 5 has been shown to localize to the …

Design, Synthesis, Application Of Biodegradable Polymers, Mussie Gide

USF Tampa Graduate Theses and Dissertations

Bacterial infections have posed a serious threat to the public health due to the significant rise of the infections caused by antibiotic-resistant bacteria. There has been considerable interest in the development of antimicrobial agents which mimic the natural HDPs, and among them biodegradable polymers are newly discovered drug candidates with ease of synthesis and low manufacture cost compared to synthetic host defense peptides. Herein, we present the synthesis of biocompatible and biodegradable polymers including polycarbonate polymers, unimolecular micelle hyperbranched polymers and dendrimers that mimic the antibacterial mechanism of HDPs by compromising bacterial cell membranes. The developed amphiphilic polycarbonates are highly …

The Effect Of Ammonia On The Germination And Outgrowth Of Bacillius Globigii, Joseph B. Kunicki

Theses and Dissertations

This research investigated the germination and outgrowth of Bacillus globigii in the presence of ammonia in laboratory scale experiments. Germination was measured by monitoring the release of dipicolinic acid, an organic compound present in bacterial spores, while outgrowth was measured using phase-bright microscopy and semi-automated counting procedures. The ammonia-N concentrations investigated generally did not cause statistically significant differences in the initial 1-hr germination rates or the average 3-hr outgrowth rates of Bacillus globigii spores in batch style experiments. The average 1-hr germination rates observed in the absence of ammonia-N was 0.0258 hr^-1 for the water and buffer controls and …

Investigating The Synthesis Of 1,3,4-Oxadiazoles Via A Novel Two-Step-One-Pot Cyclodehydration Reaction, Brittney Sowers

Undergraduate Honors Thesis Projects

The given research will investigate synthetic strategies and differential functionalization of 1,3,4- oxadiazoles in hopes of obtaining moderate to high yields. Particularly, the effects of electron withdrawing on oxadiazoles will reveal more information about possible mechanistic details and reaction optimization.

The research in this report is a part of a lager research effort being investigated by Dr. Robin Grote. This research is ongoing and has evolved from its start in the Grote Lab. Previously, the Grote Lab has focused on the formation of a patented heterocycle that contained an amino-pyrazine functional group. Currently, our research has shifted focus to the …

Profiling Prostate Cancer Therapeutic Resistance, Cameron A. Wade, Natasha Kyprianou

Urology Faculty Publications

The major challenge in the treatment of patients with advanced lethal prostate cancer is therapeutic resistance to androgen-deprivation therapy (ADT) and chemotherapy. Overriding this resistance requires understanding of the driving mechanisms of the tumor microenvironment, not just the androgen receptor (AR)-signaling cascade, that facilitate therapeutic resistance in order to identify new drug targets. The tumor microenvironment enables key signaling pathways promoting cancer cell survival and invasion via resistance to anoikis. In particular, the process of epithelial-mesenchymal-transition (EMT), directed by transforming growth factor-β (TGF-β), confers stem cell properties and acquisition of a migratory and invasive phenotype via resistance to anoikis. Our …

5-Lipoxygenase (5-Lox)-5-Lipoxygenase Activating Protein (Flap)-Nanodisc Complex: A Model For The 5-Lox-Flap Interaction, Erin Elizabeth Schexnaydre

LSU Doctoral Dissertations

Leukotrienes (LT) are lipid mediators of the inflammatory response that play important roles in diseases such as asthma and atherosclerosis. Leukotriene A4 (LTA₄) is synthesized from arachidonic acid (AA) by 5-lipoxygenase (5-LOX) with the help of 5-lipoxygenase activating protein (FLAP), a trimeric nuclear transmembrane protein. Exactly how 5-LOX and FLAP interact is not well understood, however FLAP is essential for the production of leukotrienes in vivo. I used nanodiscs (NDs), engineered membrane systems, as a tool to study the 5-LOX-FLAP interaction. FLAP was incorporated into NDs with a phospholipid composition to mimic of the nuclear membrane. Structural features …

A Chimeric Nucleobase - Phenylazo Derivative As An Intrinsic Nucleobase Quencher, Gyeongsu Park, Timothy Martin-Chan, Amer El Samm, Robert H.E. Hudson

Western Research Forum

Molecular beacons are important bioanalytical probes which are most often

constructed from a single-stranded oligonucleotide which has been labeled at

opposite termini with a fluorophore and a quencher. When the fluorophore and

quencher are in close proximity, no fluorescence is observed due to FRET

(Fluorescence Resonance Energy Transfer). DABCYL (4-dimethylaminoazobenzene-

4'-carboxylic acid) has been used as a quencher in the molecular beacon to absorbs

excitation energy from a fluorophore and to dissipate the energy as heat. However,

DABCYL is unable to form a base-pair and is conventionally placed as an overhanging

residue. This produces a derivative wherein the chromophore has …

Role Of Pu.1 And C/Ebpα In Remodelling The Interleukin (Il)-1Β Enhancer-Promoter Interaction, Woohyun Cho, Soon-Duck Ha, Sung Ouk Kim

Western Research Forum

Background: IL-1b is a potent inflammatory cytokine promptly expressed in activated myeloid immune cells. Among various transcription factors, PU.1 and CCAAT/enhancer-binding protein alpha (C/EBPa) play a key role in the lineage commitment of myeloid cells. To date, however, the exact mechanisms by which these lineage-determining transcription factors employ to regulate the expression of myeloid-specific genes remains elusive; thus, this study explores the role of PU.1 and C/EBPa in remodelling the chromatin conformation that allows ample production of IL-1b.

Methods: To examine the mechanism of these lineage-determining transcription factors, production of IL-1b and enhancer-promoter interactions were analyzed in non-myeloid B16-BL6 cells …

Developing Novel Therapeutics For Bacterial Lung Infections, Brandon J. Baer, Ruud Veldhuizen, Cory Yamashita

Western Research Forum

Background: Bacterial lung infections are leading causes of death worldwide. Unfortunately, increasing resistance to antibiotics and the inflammation often accompanying these infections are leading to poor outcomes despite antibiotic intervention. Complicating treatment further, the tree-like branching structure of the lung makes drug delivery to distal sites of infection difficult. Our research aims to address these challenges by developing new therapeutics and new tools to improve and assess drug delivery, bacterial killing and inflammation. Our therapy combines host defense peptides, which have been shown to kill antibiotic-resistant bacteria and down regulate inflammation, with a pulmonary vehicle, exogenous surfactant, that can improve …