Life Sciences Commons^™

Pcb126 Exposure During Pregnancy Alters Maternal And Fetal Gene Expression, Cetewayo S. Rashid, Joshua D. Preston, Sara Y. Ngo Tenlep, Marissa K. Cook, Eric M. Blalock, Changcheng Zhou, Hollie I. Swanson, Kevin J. Pearson

Markey Cancer Center Faculty Publications

Polychlorinated biphenyls (PCBs) are organic pollutants that can have lasting impacts on offspring health. Here, we sought to examine maternal and fetal gene expression differences of aryl hydrocarbon receptor (AHR)- regulated genes in a mouse model of prenatal PCB126 exposure. Female mice were bred and gavaged with 1 μmole/kg bodyweight PCB126 or vehicle control on embryonic days 0 and 14, and maternal and fetal tissues were collected on embryonic day 18.5. Total RNAs were isolated, and gene expression levels were analyzed in both maternal and fetal tissues using the NanoString nCounter system. Interestingly, we found that the expression levels of …

Portable Optical Spectroscopic Assay For Non-Destructive Measurement Of Key Metabolic Parameters On In Vitro Cancer Cells And Organotypic Fresh Tumor Slices, Jing Yan, Carlos Frederico Lima Goncalves, Madison O. Korfhage, Zahid Hasan, Teresa Whei-Mei Fan, Xiaoqin Wang, Caigang Zhu

Markey Cancer Center Faculty Publications

To enable non-destructive metabolic characterizations on in vitro cancer cells and organotypic tumor models for therapeutic studies in an easy-to-access way, we report a highly portable optical spectroscopic assay for simultaneous measurement of glucose uptake and mitochondrial function on various cancer models with high sensitivity. Well-established breast cancer cell lines (MCF-7 and MDA-MB-231) were used to validate the optical spectroscopic assay for metabolic characterizations, while fresh tumor samples harvested from both animals and human cancer patients were used to test the feasibility of our optical metabolic assay for non-destructive measurement of key metabolic parameters on organotypic tumor slices. Our optical …

Structures Of The Insecticidal Toxin Complex Subunit Xpta2 Highlight Roles For Flexible Domains, Cole L. Martin, David W. Chester, Christopher D. Radka, Lurong Pan, Zhengrong Yang, Rachel C. Hart, Elad M. Binshtein, Zhao Wang, Lisa Nagy, Lawrence J. Delucas, Stephen G. Aller

Markey Cancer Center Faculty Publications

The Toxin Complex (Tc) superfamily consists of toxin translocases that contribute to the targeting, delivery, and cytotoxicity of certain pathogenic Gram-negative bacteria. Membrane receptor targeting is driven by the A-subunit (TcA), which comprises IgG-like receptor binding domains (RBDs) at the surface. To better understand XptA2, an insect specific TcA secreted by the symbiont X. nematophilus from the intestine of entomopathogenic nematodes, we determined structures by X-ray crystallography and cryo-EM. Contrary to a previous report, XptA2 is pentameric. RBD-B exhibits an indentation from crystal packing that indicates loose association with the shell and a hotspot for possible receptor binding or a …

The Role Of Vaccination Route With An Adenovirus-Vectored Vaccine In Protection, Viral Control, And Transmission In The Sars-Cov-2/K18-Hace2 Mouse Infection Model, Alexandria Dickson, Elizabeth Geerling, E. Taylor Stone, Mariah Hassert, Tara L. Steffen, Taneesh Makkena, Madeleine Smither, Katherine E. Schwetye, Jianfeng Zhang, Bertrand Georges, M. Scot Roberts, John J. Suschak, Amelia K. Pinto, James D. Brien

Markey Cancer Center Faculty Publications

Introduction: Vaccination is the most effective mechanism to prevent severe COVID-19. However, breakthrough infections and subsequent transmission of SARS-CoV-2 remain a significant problem. Intranasal vaccination has the potential to be more effective in preventing disease and limiting transmission between individuals as it induces potent responses at mucosal sites.

Methods: Utilizing a replication-deficient adenovirus serotype 5-vectored vaccine expressing the SARS-CoV-2 RBD (AdCOVID) in homozygous and heterozygous transgenic K18-hACE2, we investigated the impact of the route of administration on vaccine immunogenicity, SARS-CoV-2 transmission, and survival.

Results: Mice vaccinated with AdCOVID via the intramuscular or intranasal route and subsequently challenged with SARS-CoV-2 showed …

The S1p Receptor 1 Antagonist Ponesimod Reduces Tlr4-Induced Neuroinflammation And Increases Aβ Clearance In 5xfad Mice, Zhihui Zhu, Liping Zhang, Ahmed Elsherbini, Simone M. Crivelli, Priyanka Tripathi, Carmen Harper, Zainuddin Quadri, Stefka D. Spassieva, Erhard Bieberich

Markey Cancer Center Faculty Publications

Background Previously, we showed that the sphingosine-1-phosphate (S1P) transporter spinster 2 (Spns2) mediates activation of microglia in response to amyloid β peptide (Aβ). Here, we investigated if Ponesimod, a functional S1P receptor 1 (S1PR1) antagonist, prevents Aβ-induced activation of glial cells and Alzheimer’s disease (AD) pathology.

Methods We used primary cultures of glial cells and the 5XFAD mouse model to determine the effect of Aβ and Ponesimod on glial activation, Aβ phagocytosis, cytokine levels and pro-inflammatory signaling pathways, AD pathology, and cognitive performance.

Findings Aβ42 increased the levels of TLR4 and S1PR1, leading to their complex formation. Ponesimod prevented the …

Acute Responses To Combined Accentuated Eccentric Loading And Rest Redistribution, Sungwon Chae

Electronic Theses and Dissertations

This dissertation was 2 parts of investigations of various acute responses to high-volume combined accentuated eccentric loading and rest redistribution (AEL + RR). Resistance-trained men (n = 12, 25.6 ± 4.4 years, 1.77 ± 0.06 m, 81.7 ± 11.4 kg) completed a back squat (BS) 1 repetition maximum (1RM) and weight releaser familiarization session. Three BS exercise conditions (sets × repetitions × eccentric/concentric loading) comprised AEL + RR 5: 3 × (5 × 2) × 110/60%, AEL + RR 2: 3 × (2 × 5) × 110/60%, and traditional sets (TS): 3 × (1 × 10) × 60/60% 1RM. The …

Mississippi Career And Technical Education Teachers’ Perception Toward Implementing A Food Science Toolkit Designed To Increase Food Science Curriculum Use In Mississippi, Jasmine D. Hendrix, Wes Schilling, Laura H. Downey, Yan Campbell, Shecoya White

Journal of Human Sciences and Extension

A pilot test implementing a food science toolkit designed to increase student awareness, interest, and knowledge of food science academic and career pathways in Mississippi Career and Technical Education (CTE) courses was conducted to determine teachers’ perceptions of the food science education resources. After implementing the food science toolkit in their CTE course, four teachers individually participated in a semi-structured interview to capture each teacher’s detailed experience implementing the food science toolkit. The results of this study revealed that teachers are interested in teaching food science at the secondary education level to increase student knowledge of food science and enhance …

Heterogeneity Among Harveyi Clade-Specific Virulence Genes And Attribution Of These Genes To Possible Environmental Carriers, Cameron Brown

Biology Theses

In the face of global warming, waterborne pathogens are evolving rapidly and expanding geographically. The Vibrio Harveyi clade encompasses a number of human and aquatic organism pathogens, and due to their physiology, they may benefit from ongoing changes in the temperature, pH, and salinity of the global Ocean. With this, the Southeastern United States might become an accommodating environment for Harveyi clade species, and it is imperative to monitor for their abundance and distribution in the environment. A qPCR assay was developed for the detection and quantification of clade-specific virulence genes toxRvh, hly, toxR, luxR, srp, vhha, vhh, and vhp …

Investigating The Distinct Role Of Pd-L2 In Modulating Human T Cells Responses, Anupallavi Srinivasamani

Dissertations and Theses (Open Access)

INVESTIGATING THE DISTINCT ROLE OF PD-L2 IN MODULATING HUMAN T CELL RESPONSES

Anupallavi Srinivasamani, M.S.

Advisory Professor: Michael A. Curran, Ph.D.

Therapeutic blockade of the Programmed cell death-1 (PD-1) receptor and its ligand Programmed death ligand-1 (PD-L1) has revolutionized the treatment of multiple cancers and made durable tumor regression a possibility in the clinic. PD-1 blockade prolonged progression-free survival and overall survival with lesser high-grade toxicity in patients with advanced melanoma when compared to the other FDA-approved checkpoint blockade target, CTLA-4. Unlike CTLA-4, PD-1 is unique in its ability to regulate T cell functions in lymphoid tissues as well as …

Genetic Analysis Of Crossover Defective Mouse Spermatocytes Reveals Discrete Crossover Precursor Intermediates, Tolkappiyan Prem Kumar

Dissertations and Theses (Open Access)

In healthy, non-replicating somatic cells of diploid organisms, like humans and mice, there are two copies of each chromosome, one from each parent. However, the germ cells of these organisms, the oocytes, and the sperm, have only one copy of each chromosome, thus ensuring that when haploid oocytes and sperm fuse to form a zygote, a diploid number of chromosomes is restored. The reduction of a diploid number of chromosomes to a haploid number of chromosomes takes place during meiosis. The meiotic cell cycle consists of two rounds of cell division, Meiosis I and Meiosis II. Meiosis I create haploid …

Landscape Of Ecdna-Borne Non-Coding Rnas In Glioblastoma, Dexin Yang

Dissertations and Theses (Open Access)

Recent advances in cancer genetics found that strong oncogene transcription can occur on a form of non-chromosome DNAs that is often amplified to tens or hundreds of copies, and that can exist in more than half of cancer types. This type of genetic material was termed extrachromosomal DNA (ecDNA). ecDNA appears to be epigenetically highly accessible and transcriptionally active compared with chromosomal DNA, which may partially underlie their critical roles in driving oncogene overexpression and cancer evolution. However, the full molecular mechanisms and regulators that confer the exceptional transcriptional activity of ecDNA-associated genes are incompletely understood.

Enhancers are key genetic …

Therapeutic Potential Of Prmt5 And Mat2a As Synthetic Lethal Targets In Mtap-Deficient Gbm Tumors, Yasaman Barekatain

Dissertations and Theses (Open Access)

Homozygous deletion of methylthioadenosine phosphorylase (MTAP) is a frequent genetic alteration found in approximately 15% of all human cancers, including glioblastoma, pancreatic cancer, mesothelioma, urothelial bladder carcinoma, and lung squamous cell carcinoma. MTAP is a critical metabolic enzyme in the methionine salvage pathway responsible for the breakdown of methylthioadenosine (MTA). As a result, MTAP-deleted cells cannot metabolize MTA, leading to the accumulation of MTA. High levels of MTA in MTAP-deleted cells partially inhibit the activity of protein arginine methyltransferase 5 (PRMT5), making these cells sensitive to PRMT5 and MAT2A inhibition. Although elevated levels of MTA in …

Acute Manipulation Of Erna Level For Dissecting Its Roles In Transcriptional Regulation, Lanxin Bei

Dissertations and Theses (Open Access)

Enhancers are the central genetic elements controlling cell-type and state specific transcription programs to dictate cell fates during development. Mechanistic understanding of enhancer action is important for both biology and disease research. In the human genome, more than 60k human enhancers were found to produce non-coding transcripts named enhancer RNAs (eRNAs). These created a new challenge to understand enhancer functions, which now are not only DNA elements that promote transcription but also RNA-producing transcription units themselves. Importantly, deregulation of eRNAs was associated with various diseases such as cancer, immune disorders, and neurodegeneration. However, the direct role of eRNAs in transcriptional …

Molecular Mechanisms Behind Sars-Cov-2 Induced Host Genome Restructuring, Erin Simpson

Dissertations and Theses (Open Access)

Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2) has caused unprecedented morbidity and mortality worldwide. There are two pathophysiological hallmarks associated with severe patient outcomes after SARS-CoV-2 acute infection, namely delayed/weakened interferon production and overactive inflammatory responses. Our previous work has shown that these altered immune responses are due, at least in part, to significant alterations in 3D genome organization and epigenetic landscape following SARS-CoV-2 infection that are distinct from and more severe than changes caused by other viral infections or immune stimulants. While these changes at the chromatin level are important for understanding the immune dysregulation seen in some cases …

Unveiling Immune Checkpoint Therapy Resistance Mechanisms In The Tumor Microenvironment Using High-Dimensional Analyses, Swetha Anandhan

Dissertations and Theses (Open Access)

The advent of immune checkpoint therapy (ICT) has transformed cancer treatment, but its effectiveness is limited in certain cancers like pancreatic ductal adenocarcinoma (PDAC), which exhibit resistance to this therapy. To overcome this challenge, it is crucial to understand the underlying mechanisms that determine tumor response to ICT and develop rational therapeutic combinations. The tumor microenvironment (TME), including suppressive myeloid cells, regulatory T cells (Tregs), and cancer-associated fibroblasts (CAFs), plays a pivotal role in ICT responses. Leveraging single-cell technologies, this study explores the role and function of immune subsets in the TME that induce therapy resistance.

Using single-cell RNA sequencing …

Protein L Functionalized Microparticles For Early Detection Of Surface Markers In Heterogeneous Colorectal Lesions, Saleh Ramezani

Dissertations and Theses (Open Access)

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths among both men and women worldwide, a statistic that can be improved with early detection. Increased understanding of the tumor landscape has identified surface antigens that can be utilized to distinguish normal and cancerous tissue lining the colonic lumen. Use of antibodies conjugated to nano/micromaterials offers a means to detect these antigens, however, the heterogeneous nature of tumors makes it unlikely that antibodies against a single antigen will have sufficient sensitivity and specificity to detect all tumors. A versatile micromaterial able to be functionalized with more than one targeting …

Role Of Il-17/Il-17ra Signaling In The Pancreatic Tumor Microenvironment, Susana Castro Pando, Susana Castro Pando

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second leading cause of cancer-related deaths. PDAC is characterized by the early establishment of a highly immunosuppressive fibro-cellular tumor microenvironment (TME). Our research has revealed the important role of IL-17 in the development and progression of pancreatic cancer, yet the specific cellular compartment responsible for IL-17-mediated tumor promotion remains unknown. We generated a transgenic mouse model with pancreatic KrasG12D activation and selective deletion of IL-17RA in the epithelial vs. immune component using either genetic manipulation or bone marrow transplantation. Deletion of IL17RA from the pancreatic epithelial compartment delayed premalignant lesion development …

Investigating The Role Of Il-10 Producing Nkt Cells In Prevention Of Graft Versus Host Disease, Drew Boagni

Dissertations and Theses (Open Access)

The standard curative treatment for hematologic malignancies is allogeneic stem cell transplantation (ASCT), in which the patient’s immune system is replaced with that of a healthy donor. This can lead to cure through the graft versus leukemia (GVL) effect but can also cause graft versus host disease (GVHD), which is characterized by systemic inflammation and organ damage mediated by dysregulated donor T cells. Preclinical studies have shown invariant natural killer T cells (iNKT) cells can prevent GVHD while preserving GVL. iNKT cells are unconventional T cells which recognize glycolipid antigens presented in the context of CD1d. Upon activation, they secrete …

An Interdisciplinary Approach To Online Genetics Education, Pinar Ozmizrak

All Dissertations

This dissertation presents an interdisciplinary approach to online genetics education.

Chapter I provides an overview of remote education and a brief history of genetics. While the COVID-19 pandemic prompted a turn to emergency online education, exposure to this form of delivery has led to increased intentional online education.

Chapter II focuses on computer and technology use in healthcare by nursing students. This study investigated nursing students’ perspectives using a modified version of the Pretest for Attitudes Toward Computers in Healthcare (PATCH) assessment scale to explore students’ ideas about computers and technology in healthcare delivery. According to the PATCH scale, the …

Elucidating Acetate Metabolism: Identification Of Transporters And Enzymes Required For Acetate Utilization In The Fungal Pathogen Cryptococcus Neoformans, Perry L. Kezh

All Dissertations

Cryptococcus neoformans is the leading cause of fungal meningitis world-wide. While exposure to this environmental sporophyte is common during childhood, those who are immune compromised are at risk of infection. Following inhalation, this basidiomycetous fungus subsequently colonizes other organs though hematogenous dissemination, eventually crossing the blood brain barrier and colonizing the brain where it causes as cryptococcal meningitis. Changes in the availability of carbon sources stemming from the movement from soil to the lungs induce changes in fungal metabolism. Specifically, alveolar macrophages, which present a first line of defense against infection, provide a glucose-/amino acid-poor environment. As such, the use …

Evaluating Mitochondrial Dynamics And Bioenergetics In Patient-Derived Human Induced Pluripotent Stem Cells And Differentiated Derivatives Modeling Leigh Syndrome, Fibi Meshrkey

Graduate Theses and Dissertations

Mitochondrial disorders are complex diseases that involve multiple systems and result from mutations and deletions in the mitochondrial genome. Leigh syndrome (LS) is a rare and devastating primary mitochondrial disorder characterized by progressive neuromuscular degeneration. Despite its severe consequences, the clinical genotype pathophysiological underlying LS remains elusive, posing significant challenges for the development of effective therapies. The current study aims to advance our understanding of the pathology and phenotype correlation of LS by evaluating mitochondrial dynamics and bioenergetics in patient-derived human induced pluripotent stem cells (hiPSCs) and their differentiated derivatives, which serve as a reliable model of the disease. Key …

Consumer Valuation Of Rice Quality In Colombia, Juliann Phillips

Graduate Theses and Dissertations

Rice is a crucial contributor to global food security and is an important staple for over half the world’s population. In Colombia, total rice consumption has grown by 25% in the last decade (2011-2021), reaching 1.9 MMT in 2021, yet in 2021 around 15.5 million Colombians were classified as food insecure. Colombia is the third largest rice producer in Latin America, producing 1.8 million metric tons (milled basis) in 2021. Increasing rice consumption coupled with high levels of food insecurity highlights the necessity that rice markets effectively price rice according to consumer preferences. Therefore, the goal of this study focuses …

The Roles Of Estrogen Receptor Alpha-Interacting Rnas And Exosomes In Breast Cancer, And E-Cadherin In Carcinomas, Brihget Catalina Sicairos-Meza

Graduate Theses and Dissertations

Carcinomas are malignancies of epithelial cells and account for >80% of cancer-related deaths. Approximately 75% of breast cancers express estrogen receptor alpha (ERα). ERα promotes breast cancer progression by enhancing cancer cell proliferation. Tamoxifen is commonly used to treat ERα-positive breast cancers but can result in endocrine therapy resistance. The mechanisms underlying endocrine therapy resistance remain elusive. The Du lab recently found that ERα is an RNA-binding protein. However, the significance of the ERα-RNA interaction is unknown. We fractionated ERα-positive MCF7 cells into cytoplasmic and nuclear fractions, followed by immunoprecipitation of ERα with associated RNAs and RNA-sequencing. We identified many …

Lsd1-Mediated Epigenetic Reprogramming Driving Prostate Cancer Progression, Zifeng Wang

Graduate Doctoral Dissertations

Prostate cancer (PCa) is a leading cause of cancer-related deaths in men worldwide. Alterations in epigenetic regulation of gene expression have emerged as key contributors to PCa development, treatment resistance and disease progression. My thesis focuses on investigating the role of lysine-specific demethylase 1 (LSD1), a critical histone modifier, in mediating epigenetic reprogramming that drives PCa progression. The dissertation comprises three projects that elucidate the mechanisms by which LSD1 can regulate PCa progression. The first project shows that LSD1 can activate the PI3K/AKT pathway in PCa cells independent of its well-established androgen receptor (AR) coactivator function. The study identifies the …

The Effects Of Caffeine On Activity Levels And Motor Behaviors In The Honeybee, Apis Mellifera, Johana Castro

Theses and Dissertations

Caffeine is produced by plants as a defense mechanism against herbivores and pathogens. However, caffeine was found in floral nectar, which contradicts nectar's role in attracting pollinators. Interestingly, low concentrations of caffeine were shown to increase alertness and locomotion in mammals and invertebrates, indicating it may enhance the productivity of pollinators. This investigation examined how caffeine affects activity levels and motor behaviors in the honey bee, Apis mellifera. To test overall activity, forager bees were collected and fed 1 M sucrose to satiation. The following day, bees received 10 µl of 1.0 M sucrose alone or with caffeine ranging from …

Increases In Uvr Exposure: Local Adaptation Of A Bdelloid Rotifer, Maribel J. Baeza

Open Access Theses & Dissertations

Aquatic species living in ephemeral habitats without a continual influx of dissolved organic carbon (DOC) are at increased risk of the effects of ultraviolet radiation (UVR) as the climate changes. Climate change is predicted to cause changes in DOC, some habitats will experience extended periods of drought and reduced input from DOC sources, and other environmental features that increase UVR reaching aquatic habitats. UVR can cause damage to cellular structures and biomolecules such as DNA, proteins, and lipids. The pigmented bdelloid Philodina sp. (Philodina) found in rock pools in the Chihuahuan Desert naturally experiences high UVR, yet it appears to …

Diversity And Lifestyle In The Rotifera, Patrick D. Brown

Open Access Theses & Dissertations

Broad questions regarding community assembly and lifestyle evolution remain unanswered. To answer these questions I used rotifers, common primary consumers present in inland waters. Rotiferan presence in nearly all freshwaters makes them an ideal study system to address questions of metacommunity ecology. Additionally, rotifers possess diverse lifestyles, including sessile, swimming, colonial and solitary forms, allowing them to be used as models of lifestyle evolution. In Chapter 1, I address metacommunity ecology by focusing on inland waters of the Chihuahuan Desert as a study system and investigated rotifer community assembly therein through two published works, Brown et al., 2020 and 2021. …

X-Ray Crystal Structure Of E399q,E708q Ecm16 Double Mutant, Gileydis Guillama

Open Access Theses & Dissertations

The use of antibiotics has undoubtedly been a boon for humanity in combating infections and microbial threats. However, their widespread utilization has contributed to the emergence and spread of antibiotic resistance, which now poses a significant public health challenge. Streptomyces bacterium, produce diverse secondary metabolites with antibacterial, antifungal, antiviral, antitumoral, and immunosuppressant activities. Among these compounds is echinomycin, a nonribosomal peptide antibiotic synthesized by Streptomyces lasalocidi, which inhibits DNA replication and transcription by intercalating the DNA duplex at CpG steps. A gene called ecm16 was identified in the echinomycin biosynthetic gene cluster, which provides echinomycin self-resistance. Ecm16 recognizes DNA duplexes …

Immunoreactivity Of The Serotonin-Like And Fmrf-Amide-Like Nervous Systems Of Four Gnesiotrochan Rotifers, Robert Neil Walsmith

Open Access Theses & Dissertations

Reorganization of the nervous system during metamorphosis is a common phenomenon across taxa (species through phyla). In phylum Rotifera, sessile species belonging to the superorder Gnesiotrocha metamorphose from free-swimming larvae into sessile adults. Once mature, gnesiotrochan rotifers display an intricate corona or infundibulum associated with lifestyle modalities and feeding behaviors. Here, I examine serotonin-like immunoreactivity (SLIR) and FMRF-amide-like immunoreactivity (FLIR) of the gnesiotrochans Lacinularia flosculosa, Collotheca ferox, and Acyclus inquietus with a focus on life stage and sex. Based on previous research, I hypothesize that 1) innervation of the larval nervous system will vary according to the lifestyle constraints observed …

Unraveling The Biogenesis And Roles Of Iron-Sulfur Proteins During Nitrogen Fixation By Methanosarcina Acetivorans, Jasleen Saini

Graduate Theses and Dissertations

Iron-sulfur (Fe-S) clusters, the ancient cofactors found in proteins across all life forms, play vital roles in numerous cellular processes. Fe-S clusters exhibit structural diversity, ranging from simple to complex forms. Methanogens are anaerobic archaea that produce methane as a metabolic by-product through methanogenesis, a process dependent on numerous Fe-S proteins. Notably, methanogens are capable of fixing nitrogen (diazotrophy) facilitated by the enzyme complex called nitrogenase, which contains both simple and complex Fe-S clusters. While methanogens possess the largest number of Fe-S proteins, the factors involved in Fe-S cluster biogenesis remain largely unknown. Bacteria possess three distinct and well-characterized Fe-S …