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Snake Venom Peptides And Toxin Targeting The Main Protease Of Sars-Cov-2, Breauna Strawder, James Stewart, Mohammad A. Halim

Symposium of Student Scholars

The corona virus began to spread in Wuhan, China which caused it to spread worldwide creating a global pandemic in the beginning of 2020, infecting over 243 million and killing over 4.5 million people worldwide. Significant efforts were made to produce vaccines against the virus, which led the recognition of a few vaccines that has been approved by FDA. These vaccines, Pfizer-BioNTech, Moderna and Johnson & Johnson, which all have efficacy against Covid-19. Despite having vaccines, COVID-19 is still present and infecting millions and killing thousands of people every day. Multiple therapeutic options would allow us to slow down or …

Cell Penetrating Peptide Inhibiting The Main Protease Of Sars-Cov-2, Adam Ashley, James Stewart, Mohammad Halim

Symposium of Student Scholars

As of October 2021, SARS-CoV-2 has infected over 244 million people and killed about 5 million people. The current FDA approved vaccines are effective; however, they lose their effectiveness after a few months of receiving both doses of the vaccine, and it is recommended to get a booster shot six months after receiving the second dose of the vaccine. Therefore, new highly effective, long lasting antiviral agents and strategies are needed to create an alternative treatment for SARS-CoV-2 and the different variants. Previous studies have shown that cell penetrating peptides (CPPs) have led to greater efficiency of intracellular delivery. However, …

The Evolutionary Origins Of Autism Associated Genes And Their Role In Great Ape Socio-Communicative Behavior, Azeeza Abdulrauf

Master of Science in Integrative Biology Theses

Autism Spectrum Disorder (ASD) is a set of neurological disorders characterized by reduced social interactions and deficits in verbal and nonverbal communication. Although there are no clear genetic markers for ASD, studies have found associations between gene single nucleotide polymorphisms (SNPs) and patients diagnosed with ASD. For this study, the focus is on OXTR, AVPR1A, and FOXP2. OXTR is reported to regulate empathy and stress reactivity while AVPR1A is reported to regulate stress management and territorial aggression, as well as social bonding and recognition. FOXP2 is one of the first genes to be associated with both speech and language recognition …

Machine Learning-Based Risk Factor Analysis And Prevalence Prediction Of Intestinal Parasitic Infections, Ahmet Ay

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Verrucous Carcinoma Of The Vulva: Patterns Of Care And Treatment Outcomes., Sara M. Dryden, Leonid B. Reshko, Jeremy T. Gaskins, Scott R. Silva

Faculty Scholarship

Background: Verrucous vulvar carcinoma (VC) is an uncommon and distinct histologic subtype of squamous cell carcinoma (SCC). The available literature on VC is currently limited to case reports and small single institution studies. Aims: The goals of this study were to analyze data from the National Cancer Database (NCDB) to quantitate the incidence of VC and to investigate the effects of patient demographics, tumor characteristics, and treatment regimens on overall survival (OS) in women with verrucous vulvar carcinoma. Methods and results: Patients diagnosed with vulvar SCC or VC between the years of 2004 and 2016 were identified in the NCDB. …

Investigation Of Arabidopsis Extremophyte Relatives, Schrenkiella Parvula And Eutrema Salsugineum Reveals Different Roads Leading To Salt Stress Tolerance, Kieu-Nga Thi Tran

LSU Doctoral Dissertations

How plants adapt to salt stress has been a central question in plant biology for decades. Yet we have not been able to fully understand the molecular networks and genetic mechanisms underlying this complex trait. Most of the genetic work on salinity stress has focused on understanding salt stress responses in the leading, yet a salt-sensitive model Arabidopsis thaliana. With the recent availability of genomes for wild-relatives of A. thaliana, we can now investigate how naturally salt adapted plants may have evolved modified or novel molecular networks to adapt to salt stress. Therefore, my research utilizes a comparative …

Untargeted Lipidomics Of Non-Small Cell Lung Carcinoma Demonstrates Differentially Abundant Lipid Classes In Cancer Vs. Non-Cancer Tissue, Joshua M. Mitchell, Robert M. Flight, Hunter N. B. Moseley

Molecular and Cellular Biochemistry Faculty Publications

Lung cancer remains the leading cause of cancer death worldwide and non-small cell lung carcinoma (NSCLC) represents 85% of newly diagnosed lung cancers. In this study, we utilized our untargeted assignment tool Small Molecule Isotope Resolved Formula Enumerator (SMIRFE) and ultra-high-resolution Fourier transform mass spectrometry to examine lipid profile differences between paired cancerous and non-cancerous lung tissue samples from 86 patients with suspected stage I or IIA primary NSCLC. Correlation and co-occurrence analysis revealed significant lipid profile differences between cancer and non-cancer samples. Further analysis of machine-learned lipid categories for the differentially abundant molecular formulas identified a high abundance sterol, …

Improved Radiation Expression Profiling In Blood By Sequential Application Of Sensitive And Specific Gene Signatures, Eliseos J. Mucaki, Ben C. Shirley, Peter K. Rogan

Biochemistry Publications

Purpose. Combinations of expressed genes can discriminate radiation-exposed from normal control blood samples by machine learning based signatures (with 8 to 20% misclassification rates). These signatures can quantify therapeutically-relevant as well as accidental radiation exposures. The prodromal symptoms of Acute Radiation Syndrome (ARS) overlap those present in Influenza and Dengue Fever infections. Surprisingly, these human radiation signatures misclassified gene expression profiles of virally infected samples as false positive exposures. The present study investigates these and other confounders, and then mitigates their impact on signature accuracy.

Methods. This study investigated recall by previous and novel radiation signatures independently derived …

The Effect Of Disturbance And Invasion On Fungal And Plant Communities Over An Elevational Gradient, Adam N. Trautwig

Doctoral Dissertations

High-elevation ecosystems are at risk of disruption from the future effects of climate change. Sub-alpine meadows are a source of unique plant populations, intraspecific variation of elevationally extreme populations, and vital sources of fresh water resources. We evaluated the whole fungal communities, arbuscular mycorrhizal fungal (AMF) communities, plant communities, and edaphic variables of sub-alpine meadows in undisturbed, disturbed, and disturbed with a non-native member of the Brassicaceae (Thlaspi arvense) plots. In conjunction with measuring the effects of disturbance on native communities we conducted potting experiments on a dominant grass of sub-alpine meadows (Festuca thurberi). We also …

Monitoring Mammals At Multiple Scales: Case Studies From Carnivore Communities, Kadambari Devarajan

Doctoral Dissertations

Carnivores are distributed widely and threatened by habitat loss, poaching, climate change, and disease. They are considered integral to ecosystem function through their direct and indirect interactions with species at different trophic levels. Given the importance of carnivores, it is of high conservation priority to understand the processes driving carnivore assemblages in different systems. It is thus essential to determine the abiotic and biotic drivers of carnivore community composition at different spatial scales and address the following questions: (i) What factors influence carnivore community composition and diversity? (ii) How do the factors influencing carnivore communities vary across spatial and temporal …

Discovering Mechanisms Driving Adaptive Evolution In The Cross-Kingdom Fungal Pathogen Fusarium Oxysporum, Dilay Hazal Ayhan

Doctoral Dissertations

Fusarium oxysporum is a cross-kingdom pathogenic fungus that can cause vascular wilt disease in many economically important plants and local or disseminated infections in humans. Although it lacks a sexual stage in its life cycle, F. oxysporum can adapt to a wide range of hosts because of accessory chromosomes (ACs) which are enriched in host-specific genes and repeat content. This dissertation investigates the mechanisms that drive the adaptive evolution in the cross-kingdom pathogen F. oxysporum using comparative genomics and an experimental evolution approach. The first chapter compares phenotypes and genomes of a plant pathogenic isolate F. oxysporum f. sp. lycopersici …

Human 5’-Tailed Mirtrons Are Processed By Rnasep, Mohammad Farid Zia

Dissertations

Approximately a thousand microRNAs (miRNAs) are documented from human cells. A third appear to transit non-canonical pathways that typically bypass processing by Drosha, the dedicated nuclear miRNA producing enzyme. The largest class of non-canonical miRNAs are mirtrons which eschew Drosha to mature through spliceosome activity. While mirtrons are found in several configurations, the vast majority of human mirtron species are 5’-tailed. For these mirtrons, a 3’ splice site defines the 3’ end of their hairpin precursor while a “tail” of variable length separates the 5’ base of the hairpin from the nearest splice site. How this tail is removed is …

Determining The Primary Dna Substrates Of Shld2'S Ob-Fold Domains, Hari Patchigolla

Holster Scholar Projects

Failure to repair DNA double-stranded breaks leads to cell death. Radiation therapy is commonly used to kill cancer cells by inducing these breaks. However resistance to radiation therapy, due to a hyperactive DNA double-stranded break repair pathway, is a common occurrence that makes cancer patients more prone to relapse. The Shieldin complex is shown to promote DNA-double stranded break repair by binding to DNA at sites of damage. Thus, the objective of this project is to understand the affinity and type of DNA that Shieldin binds to, through gel-shift assays, for the eventual creation of an inhibitor for this protein …

Investigating The Impact Of Land Use On Avian Diversity And Abundance In Areas Surrounding Mabamba Swamp, Uganda, Sydney Marie Jones

Independent Study Project (ISP) Collection

The primary objective of this study was to investigate the impact of wetland-adjacent land use on avian species richness and abundance areas surrounding Mabamba Swamp, Uganda. Four types of land use were investigated: Eucalyptus plantations, wetland-edge agricultural fields, residential areas, and mature secondary forests. A total of 40-morning point counts were conducted for ten days in late November and late December of 2021. One-way ANOVA tests and Tukey’s HSD tests revealed significant differences in mean avian richness and abundance between all sites except residential areas and Nkima Forest. Additionally, Nkima Forest was found to contain the most number of specialist …

A Network-Based Approach For Computational Drug Repurposing On Cancer Data, Ann Reba, Thomas Alexander

Electronic Theses and Dissertations

In this thesis, we are interested in finding the best drugs that can be repurposed for the disease and able to find the adverse effects such drugs that are FDA-Approved. Developing an effective drug can be a time-consuming and expensive crucible method. Network-based machine learning methods are used for predicting a given drug for A that can be used for B. It aims at finding new indications for already existing drugs and therefore increases the available therapeutic choices at a fraction of the cost of new drug development. The perturbation gene expression data corresponding to the MCF7 cell line was …

Deep Learning Applications In Medical Bioinformatics, Ziad Omar

Electronic Theses and Dissertations

After a patient’s breast cancer diagnosis, identifying breast cancer lymph node metastases is one of the most important and critical factor that is directly related to the patient’s survival. The traditional way to examine the existence of cancer cells in the breast lymph nodes is through a lymph node procedure, biopsy. The procedure process is time-consuming for the patient and the provider, costly, and lacks accuracy as not every lymph node is examined. The intent of this study is to develop an artificial neural network (ANNs) that would map genetic biomarkers to breast lymph node classes using ANNs. The neural …

Covid-19 In Silico Drug With Zingiber Officinale Natural Product Compound Library Targeting The Mpro Protein, Renadya Maulani Wijaya, Muhammad Aldino Hafidzhah, Viol Dhea Kharisma, Arif Nur Muhammad Ansori, Arli Aditya Parikesit

Makara Journal of Science

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide pandemic. Ginger (Zingiber officinale) is a rhizome, which is commonly used for culinary and medicinal purposes. In Indonesia, ginger is taken as traditional medicine by processing it into a drink known as jamu. The present study aimed to assess and evaluate the bioactive compounds in ginger that can be used in drug design for treating COVID-19. The crystal structure of the SARS-CoV-2 main protease (M^pro) was generated from a protein sequence database, i.e., Protein Data Bank, …

Discretized Geometric Approaches To The Analysis Of Protein Structures, John Holland

Dartmouth College Ph.D Dissertations

Proteins play crucial roles in a variety of biological processes. While we know that their amino acid sequence determines their structure, which in turn determines their function, we do not know why particular sequences fold into particular structures. My work focuses on discretized geometric descriptions of protein structure—conceptualizing native structure space as composed of mostly discrete, geometrically defined fragments—to better understand the patterns underlying why particular sequence elements correspond to particular structure elements. This discretized geometric approach is applied to multiple levels of protein structure, from conceptualizing contacts between residues as interactions between discrete structural elements to treating protein structures …

Identifying Inhibitors Targeting The Nonstructural Protein 15 And Main Protease Of Coronaviruses Using Molecular Docking And Molecular Dynamics Simulation, Nakoa Kristen Webber

Theses and Dissertations

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2020 has impacted daily life globally for over a year. While multiple vaccines have been authorized for emergency use and one oral medication has entered clinical trials, we are still seeking antiviral drugs for a long-term treatment for SARS-CoV-2 as well as other coronaviruses. Computational drug screenings of two SARS-CoV-2 protein target candidates are presented in this thesis: the nidoviral RNA uridylate-specific endoribonuclease (Nsp15) and the main protease (Mpro) of SARS-CoV-2. Nonstructural proteins of coronaviruses were selected as targets as they are more conserved across coronavirus strains than …

Real-World Evaluation Of Universal Germline Screening For Cancer Treatment-Relevant Pharmacogenes, Megan L. Hutchcraft, Nan Lin, Shulin Zhang, Catherine Sears, Kyle Zacholski, Elizabeth A. Belcher, Eric B. Durbin, John L. Villano, Michael J. Cavnar, Susanne M. Arnold, Frederick R. Ueland, Jill M. Kolesar

Pathology and Laboratory Medicine Faculty Publications

The purpose of this study was to determine the frequency of clinically actionable treatment-relevant germline pharmacogenomic variants in patients with cancer and assess the real-world clinical utility of universal screening using whole-exome sequencing in this population. Cancer patients underwent research-grade germline whole-exome sequencing as a component of sequencing for somatic variants. Analysis in a clinical bioinformatics pipeline identified clinically actionable pharmacogenomic variants. Clinical Pharmacogenetics Implementation Consortium guidelines defined clinical actionability. We assessed clinical utility by reviewing electronic health records to determine the frequency of patients receiving pharmacogenomically actionable anti-cancer agents and associated outcomes. This observational study evaluated 291 patients with …

Random Forest-Integrated Analysis In Ad And Late Brain Transcriptome-Wide Data To Identify Disease-Specific Gene Expression, Xinxing Wu, Chong Peng, Peter T. Nelson, Qiang Cheng

Sanders-Brown Center on Aging Faculty Publications

Alzheimer's disease (AD) is a complex neurodegenerative disorder that affects thinking, memory, and behavior. Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a recently identified common neurodegenerative disease that mimics the clinical symptoms of AD. The development of drugs to prevent or treat these neurodegenerative diseases has been slow, partly because the genes associated with these diseases are incompletely understood. A notable hindrance from data analysis perspective is that, usually, the clinical samples for patients and controls are highly imbalanced, thus rendering it challenging to apply most existing machine learning algorithms to directly analyze such datasets. Meeting this data analysis challenge is …

Bone Quality And Fractures In Women With Osteoporosis Treated With Bisphosphonates For 1 To 14 Years, Hartmut H. Malluche, Jin Chen, Florence Lima, Lucas J. Liu, Marie-Claude Monier-Faugere, David A. Pienkowski

Internal Medicine Faculty Publications

Oral bisphosphonates are the primary medication for osteoporosis, but concerns exist regarding potential bone-quality changes or low-energy fractures. This cross-sectional study used artificial intelligence methods to analyze relationships among bisphosphonate treatment duration, a wide variety of bone-quality parameters, and low-energy fractures. Fourier transform infrared spectroscopy and histomorphometry quantified bone-quality parameters in 67 osteoporotic women treated with oral bisphosphonates for 1 to 14 years. Artificial intelligence methods established two models relating bisphosphonate treatment duration to bone-quality changes and to low-energy clinical fractures. The model relating bisphosphonate treatment duration to bone quality demonstrated optimal performance when treatment durations of 1 to 8 …

Phenotype Bias Determines How Natural Rna Structures Occupy The Morphospace Of All Possible Shapes, Fatme Ghaddar, Dr Kamaludin Dingle, Dr Petr Sulc, Prof Ard A. Louis

Undergraduate Research Symposium

The relative prominence of developmental bias versus natural selection is a long standing controversy in evolutionary biology. Here we demonstrate quantitatively that developmental bias is the primary explanation for the occupation of the morphospace of RNA secondary structure (SS) shapes. By using the RNAshapes method to define coarse-grained SS classes, we can measure the frequencies that non-coding RNA SS shapes appear in nature. Our main findings are firstly that only the most frequent structures appear in nature; the vast majority of possible structures in the morphospace have not yet been explored. Secondly, and perhaps more surprisingly, these frequencies are accurately …

Comprehensive Characterization Of Covid-19 Patients With Repeatedly Positive Sars-Cov-2 Tests Using A Large U.S. Electronic Health Record Database., Xiao Dong, Yujia Zhou, Xiao-Ou Shu, Elmer V Bernstam, Rebecca Stern, David M Aronoff, Hua Xu, Loren Lipworth

Journal Articles

In the absence of genome sequencing, two positive molecular tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) separated by negative tests, prolonged time, and symptom resolution remain the best surrogate measure of possible reinfection. Using a large electronic health record database, we characterized clinical and testing data for 23 patients with repeatedly positive SARS-CoV-2 PCR test results ≥60 days apart, separated by ≥2 consecutive negative test results. The prevalence of chronic medical conditions, symptoms, and severe outcomes related to coronavirus disease 19 (COVID-19) illness were ascertained. The median age of patients was 64.5 years, 40% were Black, and 39% …

Don't Sell Them Short, There's More To Bacterial Natural Products Than Antibiotics, Alison Clare Domzalski

Dissertations, Theses, and Capstone Projects

Recent genomic studies of microbiomes have revealed an overwhelming number of biosynthetic genes of unknown function. Most of these “cryptic” biosynthetic genes are not expressed in laboratory monocultures of individual microbes. Thus, there remains tremendous untapped potential for natural products discovery. Here we employ mixed microbial culture (MMC) as a simple yet powerful approach to awaken cryptic biosynthetic gene clusters. Our preliminary studies demonstrated that arrays of metabolites could be induced in MMCs upon environmental cues, such as surface adhesion. Using this system, we have screened, identified, and isolated bioactive bacterial metabolites, which were characterized structurally and biologically. Of the …

The Structural And Functional Role Of Photosensing In Rgs-Lov Proteins, Zaynab Jaber

Dissertations, Theses, and Capstone Projects

Light provides organisms with energy and spatiotemporal information. To survive and adapt, organisms have developed the ability to sense light to drive biochemical effects that underlie vision, entrainment of circadian rhythm, stress response, virulence, and many other important molecularly driven responses. Blue-light sensing Light-Oxygen-Voltage (LOV) domains are ubiquitous across multiple kingdoms of life and modulate various physiological events via diverse effector domains. Using a small molecule flavin chromophore, the LOV domain undergoes light-dependent structural changes leading to activation or repression of these catalytic and non-catalytic effectors. In silico analyses of high-throughput genomic sequencing data has led to the marked expansion …

In Silico Identification Of A Streptococcus Phage From An Unpasteurized Dairy Product

Symposium of Student Scholars

This study aimed to identify novel phages from a West African dairy product, nunu, to better understand the uncharacterized virosphere of a food microbiome. Nunu is a yogurt-like product from spontaneous fermentation of unpasteurized cow milk without a standardized starter culture. Phages and their bacterial hosts make up a microbiome, where their collective metagenome can be studied in silico, or computationally, after next generation sequencing (NGS). The targeted dataset for our study can be found in the Sequence Read Archives under the accession number of ERX2041567. This study utilized several bioinformatics software tools with customized settings: Kraken2, MetaVelvet, Edena, NCBI-BLAST, …

In Silico Isolation Of A Novel Phage For Food Safety Applications Against Pathogenic E. Coli, Daisy Mcgrath

Symposium of Student Scholars

With the advent of next-generation sequencing (NGS) on metagenomes, the elucidation of all genetic material from microbiomes has prompted a renewed interest towards uncultivated members of the virosphere. We describe the discovery of a novel phage from a metagenomic dataset on the West African fermented dairy product, nunu, with a custom bioinformatics workflow to potentially serve as a biocontrol agent against pathogenic E. coli. Initial dataset of ERR2014814 from NCBI was first subjected to Kraken2 to extract novel sequencing reads for further de novo assembly into contigs by MetaVelvet. Resultant contigs served as potential partial phage genomes, then searched …

The Evolutionary Origins Of Autism Associated Genes And Their Role In Great Ape Socio-Communication, Azeeza Abdulrauf, Martin Hudson, Susan M.E. Smith, Jared P. Taglialatela

Symposium of Student Scholars

Single nucleotide polymorphisms (SNPs) play a major role in socio-communicative behavior. For this study, the focus is on autism associated OXTR, AVPR1A, and FOXP2 SNPs, and the role they play in great apes. Prior research on the OXTR, AVPR1A, and FOXP2 SNPs show that they affect behavior skills such as understanding and controlling emotion, understanding the emotions of others, and communications skills. Great apes, such as bonobos, chimpanzees, and gorillas are the model, since they are our closest relatives in the animal kingdom capable of understanding complex communication. Each gene has at least two SNPS that are investigated in the …

Insights Into Halophilic Microbial Adaptation: Analysis Of Integrons And Associated Genomic Structures And Characterization Of A Nitrilase In Hypersaline Environments, Sarah Sonbol

Theses and Dissertations

Hypersaline environments are extreme habitats that can be exploited as biotechnological resources. Here, we characterized a nitrilase (NitraS-ATII) isolated from Atlantis II Deep brine pool. It showed higher thermal stability and heavy metal tolerance compared to a closely related nitrilase.

We also studied integrons in halophiles and hypersaline environments. Integrons are genetic platforms in which an integron integrase (IntI) mediates the excision and integration of gene cassettes at specific recombination sites. In order to search for integrons in halophiles and hypersaline metagenomes, we used a PCR-based approach, in addition to different bioinformatics tools, mainly IntegronFinder.

We found that integrons and …