Digital Commons Network^™

Effects Of Angptl3 Deficiency On The Regulation Of Hepatic Lipoprotein Production And Lipid Metabolism, Kendall Helene Burks

Arts & Sciences Graduate Student Theses and Dissertations

Cardiovascular disease is the leading cause of death worldwide. A major treatment goal is to lower plasma lipids, especially low-density lipoprotein cholesterol (LDL), the cardinal risk factor for coronary artery disease (CAD). Patients with familial hypercholesterolemia (FH) experience early-onset CAD due to extremely high LDL. Underdiagnosis and undertreatment of FH are exacerbated by limited therapeutic options. However, one strategy has successfully lowered LDL in FH patients: Inhibition of the hepatically secreted protein Angiopoietin-like protein 3 (ANGPTL3). Despite promising clinical data, the mechanism by which ANGPTL3 inhibition lowers LDL has not been fully described. Although ANGPTL3 has been shown to modulate …

Jarid2-Mediated Reprogramming Of Human Hematopoietic Progenitors For Stem Cell Transplantation, Wentao Han

Arts & Sciences Graduate Student Theses and Dissertations

Hematopoietic stem cell transplantation (HSCT) is a well-established treatment for various hematological disorders. Umbilical cord blood (UCB) has emerged as an alternative source of hematopoietic stem and progenitor cells (HSPCs). However, the limited number of functional repopulating cells in UCB units has encouraged researchers to develop methods to expand them ex vivo. Hematopoiesis is strictly regulated by epigenetic modifiers. JARID2 is a co-factor of the Polycomb Repressive Complex 2 (PRC2), which recruits the complex to specific genomic loci and promotes the deposition of Histone 3 lysine 27 trimethylation (H3K27me3), a repressive epigenetic mark that mediates condensed chromatin packing to silence …

Functional Diversification Of Rice Ago1 Proteins, Rachel Elie Jouni

Arts & Sciences Graduate Student Theses and Dissertations

Global demand for food is outpacing gains from conventional plant breeding. Scientists have turned to molecular crop breeding techniques to increase crop output and mitigate global hunger; however, a common setback in this process is the pleiotropic effects of target genes. We need to develop strategies to specifically modulate desired traits without incurring undesired penalties. Natural evolution frequently balances such tradeoffs through extensive regulation, which we can leverage to produce more specific results. Reproductive development is an important target of breeding efforts due to its direct effect on yield. Rice, a major staple food crop for half the world’s population, …

Targeting Nonsense-Mediated Rna Decay In Splicing Factor Mutant Myeloid Malignancies, Claudia Cabrera

Arts & Sciences Graduate Student Theses and Dissertations

Approximately 50% of patients with myelodysplastic syndromes (MDS) (which frequently progresses to secondary acute myeloid leukemia [AML]), 60% of chronic myelomonocytic leukemia (CMML) and 20% of de novo AML harbor heterozygous somatic mutations in spliceosome genes. We and others have shown that mutations in spliceosome genes U2AF1, SF3B1, SRSF2 and ZRSR2 cause alterations in RNA splicing, leading to production of numerous aberrant RNAs. Interestingly, spliceosome mutant cells are more sensitive to genetic alterations or drugs that further perturb RNA splicing, compared to wild-type cells. The sensitivity of spliceosome mutant cells to further perturbations in RNA splicing raises the possibility that …

Protocol For A Randomized Controlled Trial To Determine If Biomarkers Predict Response To A Pediatric Chronic Pain Symptom Management Program, Rona L Levy, Tasha B Murphy, Margaret M Heitkemper, Miranda A L Van Tilburg, Ann R Mcmeans, Jocelyn Chang, Cynthia Boutte, Katherine Lamparyk, Bruno P Chumpitazi, Robert J Shulman

Children’s Nutrition Research Center Staff Publications

Background/Objectives: Disorders of gut-brain interaction (DGBI), characterized by chronic abdominal pain and significant disability, affect 15-20% of children and adults and continue into adulthood in ~60% of cases. Costs for adults reach USD 30 billion per year, yet effective management strategies are elusive. Studies support using cognitive behavioral therapy (CBT), but abdominal pain only improves in ~40% of patients. Dietary management (low FODMAP diet; LFD) has also shown promise but it is effective in only a similar percentage of patients. Studies suggest that biologic factors (biomarkers) contribute to CBT response. Similarly, gut microbiome composition appears to influence abdominal pain …

Language Mapping During Awake Brain Surgery In A Deaf Patient With A Brain Tumor: Illustrative Case, Ene Chibawanye I, Elizabeth Silva, Kyle Noll, Mariana Bradshaw, Katherine Connelly, Ho-Ling Liu, Ravi Tummala, David Ferson, Frederick F Lang, Vinodh A Kumar

Faculty, Staff and Student Publications

Background: Signed language integrates complex sensorimotor processes involving visual and motor networks. The contribution of language regions such as Broca's and Wernicke's areas during signing is not well established. Here, the authors report the case of a 45-year-old right-handed male with congenital deafness, who communicates using American Sign Language (ASL) and Signed English, presenting with focal seizures. Imaging showed a diffuse infiltrative glioma in the right cerebral hemisphere.

Observations: Remarkably, preoperative functional MRI language activations were bihemispheric and overlapped for both traditional language paradigms and sign paradigms, suggesting that the same cortical regions of the brain are used for language …

Examing The Role Of Complement Signaling In Viral Neuroinflammatory Responses, Marlene Kanmogne

Arts & Sciences Graduate Student Theses and Dissertations

The complement system is an ancient pathway that serves dual roles as a key regulator of neuroinflammation and a critical regulator of neural networks. Few studies have addressed how these two pathways may interact during infection of the central nervous system. While some components of complement are expressed in the healthy developing brain, complement component 3a receptor (C3aR) is a G protein coupled receptor that is expressed by astrocytes, microglia and infiltrating immune cells during inflammatory states. We previously found that C3aR is required for engulfment of synaptic material by activated microglia during neuroinvasive viral infection. Here, we used a …

Acquisition Algorithms For Protein Mass Spectrometry And Their Application To Clinical Proteomics, Nathan Wamsley

Arts & Sciences Graduate Student Theses and Dissertations

Bottom-up protein mass spectrometry aims for the identification and quantification of protein species by proxy of their proteolytic peptides. This dissertation presents methodological advances in three areas of protein mass spectrometry: acquisition methods, clinical appli- cations, and data analysis algorithms. The second chapter presents an optimized internal standard-triggered parallel reaction monitoring (OIS-PRM) method and demonstrates its application to study prognostic biomarkers in head and neck squamous cell carcinoma (HN- SCC). OIS-PRM uses intelligent scan scheduling and real-time monitoring of peptide elution profiles to reduce cycle-times and improve quantitative precision and accuracy. The assay measured NRF2 activation in both cell lines …

Mutant-Specific Analysis Of Tumor Cell Heterogeneity In Glioblastoma, Patrick Desouza

Arts & Sciences Graduate Student Theses and Dissertations

Glioblastoma (GBM) is an aggressive brain tumor driven by the interplay between tumor cell-intrinsic and -extrinsic heterogeneity, enabling rapid evolution. To investigate how canonical GBM mutations promote functional plasticity, we developed an isogenic human neural stem cell (NSC) model of GBM by sequential addition of TERT promoter, TP53, and PDGFRA point mutations. TP53 loss-of-function increased TERT expression during serial mutagenesis, but only triple mutant NSCs reliably formed lethal brain tumors in vivo that recapitulate GBM. Tumor cell evolution triggered stress-related metabolic changes and transitioned toward a neuronal progenitor network driven by transcription factor INSM1. INSM1 is highly expressed in human …

Mechanisms Of Protective Humoral Immunity And Pathogenesis In Alphavirus Infection, Natasha Monir Kafai

Arts & Sciences Graduate Student Theses and Dissertations

Alphaviruses are enveloped, mosquito-transmitted, positive-sense RNA viruses of the Togaviridae family classified into Old and New World groups based on endemic regions and human disease characteristics. Old World alphaviruses, including chikungunya virus preferentially cause arthritogenic disease, whereas New World viruses like Venezuelan equine encephalitis virus (VEEV), Eastern equine encephalitis virus (EEEV), and Western equine encephalitis virus (WEEV) can cause neurological disease. Since the 1920s, VEEV has been responsible for major periodic outbreaks affecting hundreds of thousands of humans and equines in South and Central America. Expansion of mosquito vectors raises concern for possible VEEV reemergence. In addition, VEEV is a …

Proteogenomic Analysis To Inform Causal Gene Prioritization For Human Disease, Daniel Western

Arts & Sciences Graduate Student Theses and Dissertations

Genome-wide association studies (GWAS) have been key in expanding our understanding of the genetic contributions to common diseases. However, these genetic associations frequently fail to clarify causal disease mechanisms, as they often fall in non-coding regions and are difficult to interpret. One solution is to perform a GWAS for the levels of a cellular trait, known as quantitative trait locus (QTL) mapping. Through methods such as colocalization, Mendelian Randomization, and transcriptome/proteome-wide association studies, the QTL variants can be compared to disease GWAS, identifying shared variation between cellular and disease traits. We can then prioritize cellular traits as potential causative, targetable …

Birds Of A Feather: An Integrated Outdoor-Based Bird Study P-3 Curriculum Guide, Erin A. Buzza

Masters Theses/Capstone Projects

In a post-pandemic world that places technology at the at the forefront, educators are searching for ways to help students connect with the natural world. This project aids teachers in tackling this challenge by using the study of birds as a motivation to engage students with the outdoors and local wildlife. To demonstrate how ornithology topics can be used as an integrated thematic unit, research regarding components of ecological literacy is presented. They include nature-based learning, outdoor learning, environmental education, and wildlife education. In addition to these pedagogies, the benefits of incorporating interdisciplinary learning within the classroom are also provided …

Genome Wide Association Study Of Fusarium Wilt Resistance In Spinacia Turkestanica, Sanjaya Gyawali, Gehendra Bhattarai, James C. Correll, Ainong Shi, Lindsey J. Du Troit

Horticulture Faculty Publications and Presentations

Fusarium wilt of spinach, caused by Fusarium oxysporum f. sp. spinaciae (Fos), leads to substantial losses in spinach (Spinacia oleracea) seed production in the only region of the USA suitable for growing spinach seed crops, the maritime Pacific Northwest. Accessions of wild spinach, S. turkestanica, serve as a major source of resistance to multiple spinach diseases. In this study, 84 Spinacia genotypes (all 68 S. turkestanica accessions available publicly and 16 S. oleracea) were evaluated for reactions to Fos at medium and high densities of inoculum comprising a mix of isolates of races 1 and 2, using a factorial experimental …

Prognostic Value Of Serum And Bronchoalveolar Lavage Fluid Galactomannan Levels In Invasive Aspergillosis: An 8-Year Experience At A Tertiary Cancer Center, Saliba Wehbe, Anne-Marie Chaftari, Ray Hachem, Hiba Dagher, Andrea Haddad, Ann Philip, Ying Jiang, Ramia Zakhour, Peter Bakht, Jishna Shrestha, Peter Lamie, Robin Sherchan, Jennifer Makhoul, Patrick Chaftari, Issam I Raad

Faculty, Staff and Student Publications

Background: Invasive aspergillosis (IA) is a life-threatening fungal infection that primarily affects immunocompromised individuals and has high morbidity and mortality rates, necessitating timely diagnosis and treatment. This study aimed to evaluate the prognostic utility of serum and bronchoalveolar lavage (BAL) fluid galactomannan levels, as well as galactomannan kinetics, in patients with IA.

Methods: We retrospectively reviewed the medical records of patients who were diagnosed with proven or probable IA from March 2016 to April 2024 at a tertiary cancer center. The collected data included patient characteristics, baseline and peak galactomannan levels in serum and BAL fluid, galactomannan trends, and …

Volume 11 Full Text, Bjur Staff

Butler Journal of Undergraduate Research

No abstract provided.

Stress And Glucose Regulation In Adults At Risk For Type 2 Diabetes Mellitus: A Secondary Analysis From A Randomized Controlled Trial, Sophia Lysne, Regina Dispa, Brenna Way, Bea Francene Pilnade, Donya Shahamati, Romina Ballesteros, Christopher Acosta, Keren Morales, Esther Adaji, Ohis Egbaidomeh

Undergraduate Research Symposium Posters

Type 2 Diabetes Mellitus (T2DM) is a major public health concern, significantly increasing the risk of cardiovascular diseases (CVDs). Additionally, prediabetes is a critical precursor, as it elevates the risk of developing both T2DM and CVDs. (2)

Recent literature reveals among individuals with severe perceived stress, there is a higher likelihood of HbA1c% levels meeting the criteria for prediabetes (5.7– 6.4%) as compared to those with lower perceived stress. (3)

Studies show that psychological stress has hyperglycemic effects in individuals with T2DM, suggesting that stress is associated with poorer blood glucose control. (4)

Unpaired Virtual Histological Staining Of Tissue From Autofluorescence Using Regularized Cycle-Consistent Adversarial Networks, Zhesi Wen

Theses and Dissertations

We present a regularized CycleGAN with a Dense Residual U-Net to virtually stain autofluorescence images of tissue into H&E-like images. Our method outperforms standard architectures, reduces artifacts, and achieves superior FID scores, enabling efficient, label-free, and accurate digital pathology for unpaired datasets using multi-channel fluorescence inputs.

Know Thyself: A History Of Ancient Neuroscience, Alex Delano

Departmental Honors & Graduate Capstone Projects

Neuroscience is often described as one of the youngest bodies of science, but documented study of the brain begins as early as the Neolithic period. The ancient Mediterranean was a hub for science, mathematics, philosophy, and literature, all disciplines necessary for the study of the brain. Evidence of neurosurgical procedures like trepanation and craniotomy began in the Neolithic period and were practiced and improved upon throughout the ancient Mediterranean. The first detailed studies on brain anatomy were carried out in the 3^rd century BCE in Greece which created a necessary structure for future scientists to build on. While many …

Developing A Trial Unique Sequencing Task For Mice, Yader Gomez, Lilly Hagos, Gage Pompa, Ariana Mitic, Orlando Montiel, Talha Soluoku

Undergraduate Research Symposium Posters

The hippocampus and the anterior cingulate cortex (ACC) play distinct yet complimentary roles in the performance of cognitively demanding tasks.

While rodent models cannot truly capture human cognition, there is a serious need to develop more cognitively demanding rodent tasks to better understand human cognition to develop new tools to fight neurodegeneration.

Sequencing tasks are some of the most difficult for rodents to perform and are notoriously difficult to train.

Cutting edge interactive touch screen technology allows us to test an endless array of sequences, in a sound-controlled enclosure featuring a simple behavioral response for the mice.

Study Aim: To …

Marine Heat Waves Effects On Rocky Intertidal Ecosystem Functioning, Skyler Peterson, S. Schneider, C.L. Webb, A. Leighton

Undergraduate Research Symposium Posters

Severe heat waves may cause long-term changes in marine ecosystems and are expected to increase in magnitude and frequency. Here we use surveys from six localities across a six-year interval (2013-2019) to investigate the effects of heat waves on the functional diversity of rocky intertidal ecosystems (Vancouver Island, Canada).

Functional diversity, the number and types of functions performed by organisms, influences ecosystem stability and health. To assess changes in functional diversity we used analyses of biological traits. Biological traits are measurable properties of organisms that describe their morphology, physiology, and behavior. We quantitatively assessed changes in functional diversity in response …

Competence Protein Comea And Oxidative Stress In Bacillus Subtilis Stationary Phase Mutagenesis, Angeline Roldan, Sam Schauf

Undergraduate Research Symposium Posters

Stationary Phase Mutagenesis is a process where a bacterium can accumulate mutations in the absence of cell division. This may occur via competent DNA uptake and oxidant DNA damage and repair. ComEA is a transmembrane protein in B. subtilis that is required for the transport of exogenous DNA into the cell. (Figure 1)

Preparation And Characterization Of Phthalocyanine Photocatalysts Supported On Mixed Metal Oxides, Malak Alsharhan

Seton Hall University Dissertations and Theses (ETDs)

This research explores the development of hybrid photocatalysts by combining GeO₂ doping of metal oxides with phthalocyanine functionalization to enhance the degradation of Methyl Orange (MO) dye under visible light. Four metal oxide supports, TiO₂, Al₂O₃, SiO₂, and ZrO₂, were tested in their pristine form, then modified with GeO₂ and further functionalized by solution adsorption using two types of zinc phthalocyanines: F₁₆PcZn and F₆₄PcZn.

The degradation of MO was monitored using UV-Vis spectroscopy, and kinetic models were applied to evaluate the reaction rates. The results showed that the bare oxides exhibited little to no photocatalytic performance. GeO₂ doping …

Genomic Characterization Of High-Grade Serous Ovarian Carcinoma Reveals Distinct Somatic Features In Black Individuals, Katherine A Lawson-Michod, Jeffrey R Marks, Lindsay J Collin, David A Nix, Natalie R Davidson, Chad D Huff, Yao Yu, Aaron Atkinson, Courtney E Johnson, Lucas A Salas, Lauren C Peres, Casey S Greene, Joellen M Schildkraut, Jennifer A Doherty

Faculty, Staff and Student Publications

Black individuals experience worse survival after a diagnosis of high-grade serous ovarian carcinoma (HGSC) than White individuals and are underrepresented in ovarian cancer research. To date, the understanding of the molecular and genomic heterogeneity of HGSC is based primarily on the evaluation of tumors from White individuals. In the present study, we performed whole-exome sequencing on HGSC samples from 211 Black patients to identify significantly mutated genes and characterize mutational signatures, assessing their distributions by gene expression subtypes. The occurrence and frequency of somatic mutations and signatures by self-reported race were compared with historic data from The Cancer Genome Atlas …

Longitudinal Profiling Of Circulating Tumor Dna Reveals The Evolutionary Dynamics Of Metastatic Prostate Cancer During Serial Therapy, Yuehui Zhao, Naveen Ramesh, Ping Xu, Emi Sei, Min Hu, Shanshan Bai, Patricia Troncoso, Ana M Aparicio, Christopher J Logothetis, Paul G Corn, Nicholas E Navin, Amado J Zurita

Faculty, Staff and Student Publications

Treatment decisions in metastatic castration-resistant prostate cancer are mostly guided by clinical variables, but efforts to molecularly monitor the disease remain hampered by challenges in acquiring tumor tissue repeatedly. In this study, we simultaneously profiled the genome copy number and exome in longitudinal plasma circulating tumor DNA (ctDNA) acquired before, during, and upon progression to serial treatments with androgen signaling inhibitors and taxane chemotherapy from 60 patients with metastatic castration-resistant prostate cancer (2-10 samples per patient). The genomic data were used to delineate the clonal substructure and evolutionary dynamics of each patient, and an evolutionary dynamic index was developed to …

A History Of Omics Discoveries Reveals The Correlates And Mechanisms Of Loading-Induced Hypertrophy In Adult Skeletal Muscle. 2024 Camps Young Investigator Award Invited Review, Toby L. Chambers, Kevin A. Murach

Health, Human Performance and Recreation Faculty Publications and Presentations

Since the early 2000s, omics approaches to study skeletal muscle hypertrophy consequent to loading (e.g., resistance exercise) have expanded dramatically. Beginning with genomics and transcriptomics, there are now omics datasets from hypertrophying skeletal muscle spanning methylomics, proteomics, and phosphoproteomics, with further integration of single cell/nucleus-specific omics, among others. The purpose of this review is to explore the history of leveraging omics to enable understanding and discovery with respect to loading-induced hypertrophy in adult skeletal muscle. We elaborate on key historical and contemporary studies and findings, highlight specific examples where omics discoveries led to a mechanistic understanding of skeletal muscle growth, …

The Role Of Elongin B In Drosophila Melanogaster Muscle Development, Madelyne Dayan

Student Theses and Dissertations

Muscle atrophy is a result of a number of muscle diseases, as well as aging, disuse, and infections. Muscles weakened in these ways exhibit a characteristic decrease in size, strength, and mobility. The similarities between muscle in humans and Drosophila allow for direct comparisons to be made in vertebrates from studying muscle in Drosophila. Differential gene expression has been shown to play an important role in embryonic muscle development in Drosophila melanogaster. A previous study identified Elongin B (EloB) to be involved in somatic muscle morphogenesis in Drosophila, with mutant embryos displaying severe muscle defects, including thin, mis-attached, and missing …

Parsing Heterogeneity In Depression, Kayla Hannon

Arts & Sciences Graduate Student Theses and Dissertations

Depression is a highly prevalent mental health disorder that often requires treatment. While current treatments are effective for a large portion of patients generally, the exact medication that works for any specific person is unclear, leading to large delays in symptom remittance if at all. This hurdle has motivated substantial efforts to identify markers of depression that might predict treatment outcomes. However, large sources of heterogeneity in depression have stymied progress on identifying robust and replicable neuroimaging markers. Parsing this heterogeneity is crucial but mired with challenges. My dissertation work has elucidated several key barriers in parsing the heterogeneity of …

Role Of The Small Intestinal Microbiota In The Pathogenesis Of Environmental Enteric Dysfunction In Undernourished Children And Mothers, Clara Kao

Arts & Sciences Graduate Student Theses and Dissertations

Undernutrition in women and its propagation in their children remains a major global health challenge. Worldwide, one in five children under five years of age manifests undernutrition as impaired linear growth, or stunting. Stunting, defined as having a length-for-age z-score (LAZ) <-2, is associated with poor developmental outcomes, including impaired neurodevelopment and immune responses. Furthermore, stunting and its long-term sequelae persist across generations, contributing to an intergenerational cycle of undernutrition. Existing nutritional interventions fail to substantially improve stunting, highlighting the need to (i) better understand other factors contributing to stunting and (ii) focus clinical efforts towards treating maternal undernutrition. Environmental enteric dysfunction (EED) is a subclinical inflammatory enteropathy of the small intestine proposed to contribute to stunting. EED is diagnosed histologically by blunted intestinal villi, epithelial barrier disruption and an immunoinflammatory infiltrate in the lamina propria. However, the pathophysiology of EED remains poorly defined. Furthermore, the small intestinal microbiota remains understudied due to difficulties in sampling. Evidence that the small intestinal microbiota contributes to EED pathogenesis comes in part from our collaborative work with colleagues at icddr,b (the International Centre for Diarrhoeal Disease Research, Bangladesh) who oversaw the Bangladesh EED (BEED) study. In this study children, aged 12-18 months residing in an urban slum in the Mirpur district of Dhaka who failed a nutritional intervention for their stunting, underwent esophago-gastroduodenoscopy (EGD) to obtain duodenal mucosal biopsies, aspirates of duodenal luminal fluid and plasma samples. A set of 14 bacteria taxa (defined by 16S rRNA amplicon sequencing) were identified in the duodenal microbiota of >80% of children with EED. Moreover, the absolute abundances of these ‘core taxa’ were positively correlated with duodenal mucosal and systemic inflammation in study participants and negatively correlated with linear growth. Our lab showed that introduction of a consortium of bacteria cultured from these duodenal aspirates, including these core taxa, produced small intestinal inflammation in young adult gnotobiotic, providing …

Table Of Contents And Front Matter, Bjur Staff

Butler Journal of Undergraduate Research

No abstract provided.

The Anorexigenic Peptide Nesfatin-1 Dampens The B Cell Response To Receptor-Mediated Stimulation Through Inhibition Of Nf-Jb Signaling, Tara L. Steffen, Joshua D. Stafford, Colleen R. Bocke, Willis K. Samson, Gina L.C. Yosten

Biological Sciences Faculty Research & Creative Works

Nesfatin-1, a posttranslational product of the protein encoded by the nucleobindin 2 gene (NUCB2), was functionally identified as an appetite regulatory molecule in rat hypothalamic nuclei. In the years following the discovery, those findings have been corroborated and expanded upon, and we now know that nesfatin-1 is expressed throughout peripheral tissues and exerts physiological effects beyond feeding control. Literature indicates that adipose tissue is one of the peripheral sources of NUCB2/nesfatin-1, and in this setting, it has anti-inflammatory effects that have recently been implicated in regulating chronic inflammation associated with diet-induced obesity. Currently, there are gaps in our understanding of …