Digital Commons Network^™

Novel Designer Benzodiazepines: Comprehensive Review Of Evolving Clinical And Adverse Effects., Amber N. Edinoff, Catherine A. Nix, Amira S. Odisho, Caroline P. Babin, Alyssa G. Derouen, Salim C. Lutfallah, Elyse M. Cornett, Kevin S. Murnane, Adam M. Kaye, Alan David Kaye

School of Pharmacy Faculty Articles

As tranquilizers, benzodiazepines have a wide range of clinical uses. Recently, there has been a significant rise in the number of novel psychoactive substances, including designer benzodiazepines. Flubromazolam(8-bromo-6-(2-fluorophenyl)-1-methyl-4

Intermediates In Sars-Cov-2 Spike–Mediated Cell Entry, Tara C. Marcink, Thomas Kicmal, Emily Armbruster, Zhening Zhang, Gillian Zipursky, Kate L. Golub, Mohab Idris, Jonathan Khao, Jennifer Drew-Bear, Gael Mcgill, Tom Gallagher, Matteo Porotto, Amédée Des Georges, Anne Moscona

Advanced Science Research Center

SARS-CoV-2 cell entry is completed after viral spike (S) protein–mediated membrane fusion between viral and host cell membranes. Stable prefusion and postfusion S structures have been resolved by cryo–electron microscopy and cryo–electron tomography, but the refolding intermediates on the fusion pathway are transient and have not been examined. We used an antiviral lipopeptide entry inhibitor to arrest S protein refolding and thereby capture intermediates as S proteins interact with hACE2 and fusion-activating proteases on cell-derived target membranes. Cryo–electron tomography imaged both extended and partially folded intermediate states of S2, as well as a novel late-stage conformation on the pathway to …

Editorial: Mitochondria, Metabolism And Cardiovascular Diseases, Jun-Ichiro Koga, Xinghui Sun, Masuko Ushio-Fukai

Department of Biochemistry: Faculty Publications

No abstract provided.

Co-Twin Relationship Quality As A Moderator Of Genetic And Environmental Factors On Urinary Cortisol Levels Among Adult Twins, Joseph A. Schwartz, Scott Jessick, Jessica L. Calvi, Douglas A. Granger

Athletic Performance Research

Previous research has indicated that genetic and environmental factors shape physiological activity. Cortisol levels, in particular, have received significant attention, with studies indicating substantive heritability estimates across various sampling techniques. A related line of research has indicated that genetic and environmental factors that explain variability in cortisol levels may vary across context and experiences by way of gene-environment interactions (G×Es). Despite these findings, a limited number of studies have examined the extent to which interpersonal relationships may operate as a moderator. The current study focused on co-twin relationship quality as a source of moderation, as twins are more likely to …

From The Headlines: A Textual Analysis Of Social Polarization And Discord In Times Of Pandemic Across A Century In The United States, Alexa Demarco

Undergraduate Honors Theses

Within the past century, three major pandemics have affected the United States – the Spanish Flu, AIDS, and COVID-19. Each of these pandemics has tested the capabilities of the public health sector and the social resilience of the population. Scientists have studied the viruses and implemented public health measures to limit viral transmission, but the social responses to these preventative measures proved to be difficult to predict and control. The dissonance and polarization between the public health initiatives and the response of the general public in the most recent pandemic was apparent. Was this a pattern in other pandemics? Was …

Comparative Genomics And Virulence Studies Of Streptomyces Soil Rot And Scab Pathogen Species, Natasha Soares

LSU Doctoral Dissertations

Comparative genomic analyses were performed to gain insights into the organization and content of the genome of Streptomyces ipomoeae, the soil rot pathogen that infects sweetpotatoes. Unlike Streptomyces scab pathogens, the thaxtomin phytotoxin gene cluster (txt) in S. ipomoeae does not appear to reside within a genomic island and has diverged from its scab pathogen counterparts. Increased usage of the rare TTA codon, particularly for the txt cluster, suggests greater translational control by the bldA tRNA in S. ipomoeae. Orthologous gene searches and secondary metabolite profiling yielded ortholog groups and metabolite gene clusters that were exclusive …

Role Of Ligand Architecture On Collective Cell Invasion, Amrit Bagchi

McKelvey School of Engineering Graduate Student Theses & Dissertations

Epithelial cell collectives utilize extra-cellular matrix (ECM) fibers to undergo collective migration critical in regeneration, repair and cancer metastasis. However, very little is known about the various factors which determine the ability of cellular collectives to utilize ECM fibers to undergo these critical processes in-vivo. First part of the dissertation focusses on understanding how cell collectives exploit specific properties, like stiffness and fiber length to undergo collective streaming. It is also unclear how cellular forces, cell-cell adhesion, and velocities are coordinated within streams. To independently tune stiffness and collagen fiber length, we developed new hydrogels and discovered invasion-like streaming of …

Ligand- And Strain-Specific Control Of Microbial Communities, Austin Grant Rottinghaus

McKelvey School of Engineering Graduate Student Theses & Dissertations

Microbes naturally coexist in complex, multi-strain communities that are valuable assets for their host. Commensal and probiotic microbes prevent pathogen colonization, reduce the frequency and severity of various ailments, provide essential nutrients, and offer various additional benefits. Understanding the dynamics of and tailoring microbial communities to provide additional beneficial functions is a primary focus of researchers in medicine and agriculture. To date, consortia have primarily been manipulated by supplementing the communities with microbes that were engineered in vitro or by introducing stimuli that alter the metabolism or composition of the community. This method has proven successful, with numerous microbes engineered …

Collaborative Research: Developing Advanced Magnesium Electrolytes Toward Low Cost, High Energy Density Mg Batteries, Tianbiao Liu

Funded Research Records

No abstract provided.

Identification And Characterization Of Genetic Elements That Regulate A C-Di-Gmp Mediated Multicellular Trait In Pseudomonas Fluorescens, Collin Kessler

Electronic Theses and Dissertations

Microbial communities contain densely packed cells where competition for space and resources are fierce. These communities are generally referred to as biofilms and provide advantages to individual cells against immunological and antimicrobial intervention, dehydration, and predation. High intracellular pools of cyclic diguanylate monophosphate (c-di-GMP) cause cells to aggregate during biofilm formation through the production of diverse extracellular polymers. Genes that encode c-di-GMP catalytic enzymes are commonly mutated during chronic infections where opportunists display enhanced resistance to phagocytosis and antibiotics. Our lab uses an emergent multicellular trait in the model organism Pseudomonas fluorescens Pf0-1 to study the emergence of c-di-GMP mutations …

Ewing Sarcoma Transcriptome: Identification Of Foxn3 As A Novel Target Of Ews-Fli1, Natasha Kreiling

Theses & Dissertations

Ewing Sarcoma is an aggressive cancer characterized by a fusion gene formed from a chromosomal translocation between a RNA binding protein and a transcription factor. The most common fusion gene is EWS-FLI1 a potent oncogenic transcription factor responsible for initiating genome instability. EWS-FLI1 promotes tumor growth by dysregulating several genes and pathways. We have identified FOXN3, an important gene in cell cycle control and development, as being suppressed by EWS-FLI1. In the future, a better understanding of FOXN3 and its ability to act as a tumor suppressor in EWS will unravel novel mechanisms of EWS pathogenesis, potential biomarker and drug …

Dysregulation Of Mir-10a Promotes Cancer Features In Cholangiocarcinoma, Matthieu Spriet

Theses & Dissertations

Cholangiocarcinoma is a primary liver cancer of the bile duct epithelium that exhibits microRNA-mediated control of tumor cell signaling. Strides toward new treatment rest on a better defining of cholangiocarcinoma tumor biology including the RNA-based layer of regulation. Additionally, there is a gap in knowledge on microRNA expression in human tissue. While there is RNA-seq data of microRNA expression in tissue, it does not differentiate between cell types, thus leaving unanswered questions about cell specific microRNA biology and expression.

Here, we identify miR-10a as an oncogenic microRNA acting through MAPK signaling. Using cholangiocarcinoma cell lines, we determined miR-10a is an …

Neuropilin-2 In Advanced Prostate Cancer And Its Targeting With Novel Small Molecule Inhibitors, Ridwan Islam

Theses & Dissertations

Despite the development of new therapies, clinical management of advanced metastatic castrationresistant prostate cancer (mCRPC) still remains challenging owing to the emergence of therapy resistance. Resistance to the therapies is driven by both AR and non-AR pathways. Non-AR pathway is characterized by a lineage switch that leads to the development of neuroendocrine-like (NE-like) prostate cancer (PCa), which has a fulminant clinical course due to the lack of effective treatment strategy. Therefore, novel molecular targets need to be identified to develop effective therapeutic regimen to improve the outcomes in advanced PCa patients including NE-like PCa. Recent investigation on advanced PCa patients …

Quantification Of Spent Coffee Ground Extracts By Roast And Brew Method, And Their Utility In A Green Synthesis Of Gold And Silver Nanoparticles, Brian G Yust, Niny Z Rao, Evan T Schwarzmann, Madisyn H Peoples

College of Life Sciences Faculty Papers

Nanotechnology has become increasingly important in modern society, and nanoparticles are routinely used in many areas of technology, industry, and commercial products. Many species of nanoparticle (NP) are typically synthesized using toxic or hazardous chemicals, making these methods less environmentally friendly. Consequently, there has been growing interest in green synthesis methods, which avoid unnecessary exposure to toxic chemicals and reduce harmful waste. Synthesis methods which utilize food waste products are particularly attractive because they add value and a secondary use for material which would otherwise be disposed of. Here, we show that spent coffee grounds (SCGs) that have already been …

Classification Models For 2,4-D Formulations In Damaged Enlist Crops Through The Application Of Ftir Spectroscopy And Machine Learning Algorithms, Benjamin Blackburn

Theses and Dissertations

With new 2,4-Dichlorophenoxyacetic acid (2,4-D) tolerant crops, increases in off-target movement events are expected. New formulations may mitigate these events, but standard lab techniques are ineffective in identifying these 2,4-D formulations. Using Fourier-transform infrared spectroscopy and machine learning algorithms, research was conducted to classify 2,4-D formulations in treated herbicide-tolerant soybeans and cotton and observe the influence of leaf treatment status and collection timing on classification accuracy. Pooled Classification models using k-nearest neighbor classified 2,4-D formulations with over 65% accuracy in cotton and soybean. Tissue collected 14 DAT and 21 DAT for cotton and soybean respectively produced higher accuracies than the …

Qualitative Proteomic And Genomic Analysis Of Klebsiella Pneumoniae Bacteriophage Kaomega, Emilee Carr

Undergraduate Honors Theses

Klebsiella pneumoniae is a Gram-negative Enterobacteriaceae that is a common nosocomial pathogen causing pneumonia, infections in the bloodstream, wound infections, and meningitis. It has developed natural resistance to multiple antibiotics, most notably carbapenems which are often seen as the last line of defense against multi-drug resistant pathogens. Bacteriophages are being investigated as a promising alternative treatment to antibiotics in fighting these resistant pathogens. KaOmega, a Klebsiella pneumoniae bacteriophage, was isolated, sequenced, and annotated to characterize and understand its potential for use in a phage therapy. Characterization included Phyre2 analysis to predict putative protein functions based on structural homology, burst size …

A Mouse Holder For Awake Functional Imaging In Unanesthetized Mice: Applications In 31p Spectroscopy, Manganese-Enhanced Magnetic Resonance Imaging Studies, And Resting-State Functional Magnetic Resonance Imaging, Lindsay C Fadel, Ivany V Patel, Jonathan Romero, I-Chih Tan, Shelli R Kesler, Vikram Rao, S A Amali S Subasinghe, Russell S Ray, Jason T Yustein, Matthew J Allen, Brian W Gibson, Justin J Verlinden, Stanley Fayn, Nicole Ruggiero, Caitlyn Ortiz, Elizabeth Hipskind, Aaron Feng, Chijindu Iheanacho, Alex Wang, Robia G Pautler

Faculty, Staff and Students Publications

Anesthesia is often used in preclinical imaging studies that incorporate mouse or rat models. However, multiple reports indicate that anesthesia has significant physiological impacts. Thus, there has been great interest in performing imaging studies in awake, unanesthetized animals to obtain accurate results without the confounding physiological effects of anesthesia. Here, we describe a newly designed mouse holder that is interfaceable with existing MRI systems and enables awake in vivo mouse imaging. This holder significantly reduces head movement of the awake animal compared to previously designed holders and allows for the acquisition of improved anatomical images. In addition to applications in …

Continuous Fluorescence-Based Endonuclease-Coupled Dna Methylation Assay To Screen For Dna Methyltransferase Inhibitors, Rebecca Switzer, Katie A. Ward, Jessica Medrano

Faculty Journal Articles

DNA methylation, a form of epigenetic gene regulation, is important for normal cellular function. In cells, proteins called DNA methyltransferases (DNMTs) establish and maintain the DNA methylation pattern. Changes to the normal DNA methylation pattern are linked to cancer development and progression, making DNMTs potential cancer drug targets. Thus, identifying and characterizing novel small molecule inhibitors of these enzymes is of great importance. This paper presents a protocol that can be used to screen for DNA methyltransferase inhibitors. The continuous coupled kinetics assay allows for initial velocities of DNA methylation to be determined in the presence and absence of potential …

Association Between Social Vulnerability Index And Cardiovascular Disease: A Behavioral Risk Factor Surveillance System Study, Vardhmaan Jain, Mahmoud Al Rifai, Safi U Khan, Ankur Kalra, Fatima Rodriguez, Zainab Samad, Yashashwi Pokharel, Arunima Misra, Laurence S Sperling, Jamal S Rana, Waqas Ullah, Ankit Medhekar, Salim S Virani

Faculty, Staff and Students Publications

Background Social and environmental factors play an important role in the rising health care burden of cardiovascular disease. The Centers for Disease Control and Prevention developed the Social Vulnerability Index (SVI) from US census data as a tool for public health officials to identify communities in need of support in the setting of a hazardous event. SVI (ranging from a least vulnerable score of 0 to a most vulnerable score of 1) ranks communities on 15 social factors including unemployment, minoritized groups status, and disability, and groups them under 4 broad themes: socioeconomic status, housing and transportation, minoritized groups, and …

A Natural Deep Eutectic Solvent - Protonated L-Proline-Xylitol - Based Stationary Phase For Gas Chromatography, Malwina Momotko, Justyna Łuczak, Andrzej Przyjazny, Grzegorz Boczkaj

Natural Sciences Publications

The paper presents a new kind of stationary phase for gas chromatography based on deep eutectic solvents (DES) in the form of a mixture of L-proline (protonated with hydrochloric acid) as a hydrogen bond acceptor (HBA) and xylitol as a hydrogen bond donor (HBD) in a molar ratio of HBA:HBD 5:1. DES immobilized on a silanized chromatographic support was tested by gas chromatography (GC) in order to determine its resolving power for volatile organic compounds. Studies have demonstrated the suitability of this type of DES as a stationary phase for GC. The Rohrschneider-McReynolds constants were determined for the synthesized DES, …

Perturbation Modeling For Molecular Design Of Protein Tyrosine Kinase Inhibitors Using Unsupervised Machine Learning, Keerthi Krishnan

Computational and Data Sciences (MS) Theses

The field of computational drug discovery and development has grown, with the aid of new computational tools for novel molecule discovery. In specific, generative deep learning models have excelled as tools to aid in navigating the large space of known molecules and in the creation of new molecules. These models are fed various representations of molecules as inputs and learn to perform a variety of things, such as the optimization of these molecules towards a targeted property. Ultimately, these generative learning models allow us to build bridges between chemical and continuous spaces to understand the compromise between invoking small incremental …

Dual Mechanisms Implemented By Lin-28 For Positive Regulation Of Hbl-1 Are Necessary For Proper Development Of Distinct Tissues In Caenorhabditis Elegans, Madeleine Minutillo

Graduate School of Biomedical Sciences Theses and Dissertations

In Caenorhabditis elegans, the heterochronic pathway is comprised of a hierarchy of genes that control the proper timing of developmental events. hbl-1 (Hunchback Like-1) encodes an Ikaros family zinc-finger transcription factor that promotes the L2 stage cell fate events of the hypodermis. The downregulation ofhbl-1 is a crucial step for the transition from the L2 to the L3 stage. There are two known processes through which negative regulation of hbl-1 occurs: suppression of hbl-1 expression by 3 let-7 miRNAs through the hbl-1 3’UTR and inhibition of HBL-1 activity by LIN-46. The mechanisms by which hbl-1 is positively regulated have not …

The Effects Of Stress On The Mammalian Nucleolus And Ribosome Synthesis, Russell T. Sapio

Graduate School of Biomedical Sciences Theses and Dissertations

Ribosomes are responsible for translating every protein in the cell and are essential in all domains of life. Ribosome biosynthesis (RB) takes place in the nucleolus and is an intricate hierarchical process involving over 200 factors, including ribosomal proteins, ribosomal RNA (rRNA), and trans-acting ribosome biogenesis factors (RBFs). Inhibiting RB can disrupt nucleolar integrity, causing ribosomal- and nucleolar-factors to delocalize. This can stabilize the transcription factor p53, which is normally degraded rapidly, ultimately causing cell cycle arrest or apoptosis, through a mechanism termed the nucleolar stress response (NSR). This thesis explores the effects of inhibiting RB post rRNA transcription and …

Identifying A Glucocorticoid-Activated Gpcr That Rapidly And Non-Genomically Increases Camp Levels In Mammalian Cells, Francisco Nunez

Pharmaceutical Sciences (PhD) Dissertations

Glucocorticoids (GCs) are steroid hormones that regulate diverse physiological processes. Synthetic versions of GCs are commonly used to treat inflammatory diseases such as asthma by modulating gene expression to suppressing several inflammatory activities. However, it is estimated that 5-10% of asthmatics are unresponsive to GCs, which may be explained by receptor desensitization and/or the presence of a neutrophilic endotype. One understudied phenomenon of GCs is their ability to induce rapid, non-genomic actions. For example, GCs can acutely modulate calcium concentrations levels, induce smooth muscle relaxation and modulate nitric oxide synthase activity, within minutes and sometimes seconds, which is too rapid …

Investigating Granulopoiesis Of Neutrophils From Myeloblasts In The Bone Marrow Post Novel Anti-Schistosoma Compound Treatment, Sarah Alsuleiman, Paul Davis

Theses/Capstones/Creative Projects

Schistosomiasis, a commonly neglected tropical disease, is a waterborne parasitic worm infection able to infect through direct skin penetration. This disease affects approximately 270 million people worldwide and ranks only second to malaria as a leading infectious disease. Although some possible alternatives are emerging, currently, the most effective drug treatment is praziquantel (PZQ). However, PZQ is only effective against the adult stage of the worm, allowing juvenile worms to progress in the infection. Additionally, Schistosoma worms are developing resistance to this drug as reduced efficacy has been noted. Thus, the need for drug discovery and testing is increased. SA01, a …

Applications Of Nuclear Magnetic Resonance Spectroscopy: From Drug Discovery To Protein Structure And Dynamics., Mark Vincent C. Dela Cerna

Electronic Theses and Dissertations

The versatility of nuclear magnetic resonance (NMR) spectroscopy is apparent when presented with diverse applications to which it can contribute. Here, NMR is used i) as a screening/ validation tool for a drug discovery program targeting the Phosphatase of Regenerating Liver 3 (PRL3), ii) to characterize the conformational heterogeneity of p53 regulator, Murine Double Minute X (MDMX), and iii) to characterize the solution dynamics of guanosine monophosphate kinase (GMPK). Mounting evidence suggesting roles for PRL3 in oncogenesis and metastasis has catapulted it into prominence as a cancer drug target. Yet, despite significant efforts, there are no PRL3 small molecule inhibitors …

Determination Of The Functional Role Of Rab-Ggt In Physcomitrium Patens., Hyun Jin Jung

Electronic Theses and Dissertations

Protein prenylation, a common lipid post-translational modification, is required for growth and development in eukaryotes. Rab geranylgeranylation involves the addition of one or two 20-carbon geranylgeranyl moieties to Rab-GTPase target proteins, which regulate intracellular vesicle trafficking. The reaction is carried out by heterodimeric Rab geranylgeranyltransferase (Rab-GGT), which is composed of two associated α- and β-subunits, with the assistance of an additional protein called Rab escort protein (REP). Loss of function of the Rab-GGT α subunit RGTA1 has not been reported in any plant. While knockout of either of the two β subunits RGTB1 or RGTB2 results in …

Invited Perspective: Existing Rules For Disinfection By-Products Are Good, But They Are Not Enough, Susan D. Richardson

Faculty Publications

No abstract provided.

Amyloid Fibril Formation And Polymorphism : A Critical Role Of Sulfur-Containing Amino Acid Residues, Tatiana Quiñones-Ruiz

Legacy Theses & Dissertations (2009 - 2024)

Protein aggregation that results in the formation of amyloid fibrils has been linked to many neurodegenerative disorders, including Alzheimer’s disease and Parkinson’s disease. The sulfur atoms in methionine (Met) and cysteine (Cys) residues of proteins can be readily oxidized, significantly affecting their properties. Oxidation of sulfur-containing amino acids has recently been shown to affect protein fibrillation. This work presents novel findings on Cys and Met redox reactions that are related to the formation of amyloid fibrils and on the polymorphism of a model fibrillogenic protein, hen egg white lysozyme (HEWL). Biophysical techniques including Raman spectroscopy, atomic force microscopy, electron paramagnetic …

An Ims-Ms/Md Workflow For Determining Higher Order Structure And Dynamics Of Nucleic Acids, Rebecca D'Esposito

Legacy Theses & Dissertations (2009 - 2024)

Ion mobility spectrometry - mass spectrometry (IMS-MS) has potential for the investigation of structure and dynamics in large biopolymers, which will come to full fruition only with a firmer understanding of how to interpret the experimental data. Numerous studies have employed elements of nucleic acid (NA) secondary structure, such as duplexes and hairpins, to explore the relationships between structure, experimental conditions, and actual observations. When combined with molecular dynamics simulations (MDS), IMS-MS can be effectively employed to perform structural elucidation of biomolecules that are not readily amenable to established techniques employed for structural analysis.