Digital Commons Network^™

Characterization Of Pulmonary Vascular Remodeling And Microrna-126-Targets In Copd-Pulmonary Hypertension, Khushboo Goel, Nicholas Egersdorf, Amar Gill, Danting Cao, Scott D Collum, Soma S Jyothula, Howard J Huang, Maor Sauler, Patty J Lee, Susan Majka, Harry Karmouty-Quintana, Irina Petrache

Faculty, Staff and Student Publications

BACKGROUND: Despite causing increased morbidity and mortality, pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD) patients (COPD-PH) lacks treatment, due to incomplete understanding of its pathogenesis. Hypertrophy of pulmonary arterial walls and pruning of the microvasculature with loss of capillary beds are known features of pulmonary vascular remodeling in COPD. The remodeling features of pulmonary medium- and smaller vessels in COPD-PH lungs are less well described and may be linked to maladaptation of endothelial cells to chronic cigarette smoking (CS). MicroRNA-126 (miR126), a master regulator of endothelial cell fate, has divergent functions that are vessel-size specific, supporting the survival …

Review: Virtue Information Literacy: Flourishing In An Age Of Information Anarchy, Jessica A. Hawkes

Communications in Information Literacy

Review of Bivens-Tatum, W. (2022). Virtue information literacy: Flourishing in an age of information anarchy. Library Juice Press.

Outcomes In Patients With Poor-Risk Cytogenetics With Or Without Tp53 Mutations Treated With Venetoclax And Azacitidine, Daniel A Pollyea, Keith W Pratz, Andrew H Wei, Vinod Pullarkat, Brian A Jonas, Christian Recher, Sunil Babu, Andre C Schuh, Monique Dail, Yan Sun, Jalaja Potluri, Brenda Chyla, Courtney D Dinardo

Faculty, Staff and Student Publications

PURPOSE: To evaluate efficacy and safety of venetoclax + azacitidine in treatment-naïve patients with acute myeloid leukemia harboring poor-risk cytogenetics and TP53mut or TP53wt.

PATIENTS AND METHODS: We analyzed data from a phase III study (NCT02993523) comparing venetoclax (400 mg orally days 1-28) + azacitidine (75 mg/m2 days 1-7) or placebo + azacitidine, and from a phase Ib study (NCT02203773) of venetoclax + azacitidine. Patients were ineligible for intensive therapy. TP53 status was analyzed centrally; cytogenetic studies were performed locally.

RESULTS: Patients (n = 127) with poor-risk cytogenetics receiving venetoclax + azacitidine (TP53wt = 50; TP53mut = 54) were compared …

3d Imaging Analysis On An Organoid-Based Platform Guides Personalized Treatment In Pancreatic Ductal Adenocarcinoma, Ya'an Kang, Jenying Deng, Jianhua Ling, Xinqun Li, Yi-Ju Chiang, Eugene J Koay, Huamin Wang, Jared K Burks, Paul J Chiao, Mark W Hurd, Manoop S Bhutani, Jeffrey H Lee, Brian R Weston, Anirban Maitra, Naruhiko Ikoma, Ching-Wei D Tzeng, Jeffrey E Lee, Ronald A Depinho, Robert A Wolff, Shubham Pant, Florencia Mcallister, Matthew Hg Katz, Jason B Fleming, Michael P Kim

Faculty, Staff and Student Publications

BACKGROUNDPancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with unpredictable responses to chemotherapy. Approaches to assay patient tumors before treatment and identify effective treatment regimens based on tumor sensitivities are lacking. We developed an organoid-based platform (OBP) to visually quantify patient-derived organoid (PDO) responses to drug treatments and associated tumor-stroma modulation for personalized PDAC therapy.METHODSWe retrospectively quantified apoptotic responses and tumor-stroma cell proportions in PDOs via 3D immunofluorescence imaging through annexin A5, α-smooth muscle actin (α-SMA), and cytokeratin 19 (CK-19) levels. Simultaneously, an ex vivo organoid drug sensitivity assay (ODSA) was used to measure responses to standard-of-care …

Adjuvant Nab-Paclitaxel + Gemcitabine In Resected Pancreatic Ductal Adenocarcinoma: Results From A Randomized, Open-Label, Phase Iii Trial, Margaret A. Tempero, Uwe Pelzer, Eileen M. O'Reilly, Jordan Winter, Do-Youn Oh, Chung-Pin Li, Giampaolo Tortora, Heung-Moon Chang, Charles D. Lopez, Tanios Bekaii-Saab, Andrew H. Ko, Armando Santoro, Joon Oh Park, Marcus S. Noel, Giovanni Luca Frassineti, Yan-Shen Shan, Andrew Dean, Hanno Riess, Eric Van Cutsem, Jordan Berlin, Philip Philip, Malcolm Moore, David Goldstein, Josep Tabernero, Mingyu Li, Stefano Ferrara, Yvan Le Bruchec, George Zhang, Brian Lu, Andrew V. Biankin, Michele Reni

Department of Surgery Faculty Papers

PURPOSE

This randomized, open-label trial compared the efficacy and safety of adjuvant nab-paclitaxel + gemcitabine with those of gemcitabine for resected pancreatic ductal adenocarcinoma (ClinicalTrials.gov identifier: NCT01964430). METHODS

We assigned 866 treatment-naive patients with pancreatic ductal adenocarcinoma to nab-paclitaxel (125 mg/m2) + gemcitabine (1,000 mg/m2) or gemcitabine alone to one 30-40 infusion on days 1, 8, and 15 of six 28-day cycles. The primary end point was independently assessed disease-free survival (DFS). Additional end points included investigator-assessed DFS, overall survival (OS), and safety. RESULTS

Two hundred eighty-seven of 432 patients and 310 of 434 patients completed nab …

Hyperemployment: Alienated Activity, Aestheticized Precarity, And Disillusioned Techno-Optimism, Julie K. Smitka

Publications and Research

This brief reflection aims to typify hyperemployment in the digital economy as social reproduction via alienated activity, illustrate its aestheticization of precarity, and elucidate its perpetuation by techno-optimism.

Mental Health Benefits Of Physical Activity In Older Adults, Adrian Kurt Zitzmann

Master of Science in Nursing Family Nurse Practitioner

Physical activity is the fountain of youth, strengthening both the physical body as well as the mind, leading to better emotional stability and a general sense of well-being. The population over age 65 is nearing retirement age and are transitioning from a high paced work and family life to a slower and less active “empty nest” lifestyle. Among adults over age 65, will implementing an exercise program for 30 minutes per day increase mental well-being? The benefits of physical activity will be supported by gathering a group of older adults ages 65 and up from a local retirement community to …

December 2022 Bulldog Alumni & Friends News, Kari Jones, Garrett King

Bulldog Alumni & Friends News

The SWOSU Foundation, Inc. hosted a dinner last month at White Dog Hill to say farewell to departing Trustees George Cohlmia, Brice Harris, Dianne Hunter, Debbie Shepherd, Nelson Sims, and Judy Wilkes.

The Bidirectional Relationship Between The Circadian Clock And Alzheimer’S Disease, Patrick Sheehan

Arts & Sciences Graduate Student Theses and Dissertations

The circadian clock and inflammation have a well-described bidirectional relationship in the peripheral immune system: the circadian clock regulates inflammatory responses, but inflammation also impacts oscillatory gene transcription controlled by the clock. The purpose of this thesis work is to understand if manipulation of the circadian clock can impact Alzheimer’s disease pathology, and if pathology itself can alter the circadian clock and its outputs. Here, I show that astrocyte-specific disruption of the circadian clock via deletion of the clock gene Bmal1 surprisingly decreased intra-neuronal protein pathologies. Further investigation found that deletion of the circadian clock resulted in a transcriptomic profile …

Single-Cell Massively Parallel Reporter Assays, Siqi Zhao

Arts & Sciences Graduate Student Theses and Dissertations

Our understanding of gene regulation needs to be generalizable as well as specific. A generalizable understanding enables us to transfer our knowledge of one gene to another, and the specificity allows us to understand the precise regulation of gene expression through development. One framework that confers generalizability and specificity is the hierarchical and modular model of gene regulation. To test whether gene regulation is hierarchical and modular requires methods to systematically analyze how different factors collectively control gene expression. This thesis describes the development of two functional genomics methods at single-cell resolution. These methods systematically examined how cellular contexts, chromatin …

A Structural Perspective On Neutralizing Antibodies To Flaviviruses And Coronaviruses, John Michael Errico

Arts & Sciences Graduate Student Theses and Dissertations

The presence of neutralizing antibodies typically correlates strongly with protection from infection, particularly for RNA viruses; elicitation of neutralizing antibody responses is thus the primary goal of most vaccines, and monoclonal antibodies (mAbs) can be leveraged as potent therapeutics. Thus, understanding the properties of individual antibodies that comprise polyclonal antibody responses and their epitopes is essential for countermeasure design. In this dissertation, I explore the epitopes and functional properties of monoclonal antibodies targeting the structural proteins of two families of RNA viruses, flaviviruses and coronaviruses.Flaviviruses are globally distributed arthropod-borne positive-sense RNA viruses transmitted primarily by either mosquitos or ticks. Symptomatic …

The Physics Of Associative Polymers And Applications To Biomolecular Condensates, Furqan Dar

Arts & Sciences Graduate Student Theses and Dissertations

Biomolecular condensates represent a new and ubiquitous class of membraneless organelles (MLOs) that are essential for healthy cellular functioning. The constituent molecules of such condensates span a vast bio-macromolecular gamut from intrinsically disordered regions and proteins (IDPs/IDRs), to RNA and RNA-binding proteins (RNPs), to polymerases and DNA etc. Apart from being part of the regular healthy cell cycle, these condensates are also implicated in many diseases, most notably progressive neurodegenerative diseases like Amyotropic Lateral Sclerosis (ALS) and Huntingtin's Disease (HD). Since the constituent molecules of these condensates span a broad range of length scales and modes of interaction, uncovering a …

Understanding Individual Cells In Zebrafish Caudal Fin Regeneration (从单细胞视角理解斑马鱼尾鳍再生历程), Yiran Hou

Arts & Sciences Graduate Student Theses and Dissertations

Humans are incapable of complex body structure regeneration. Understanding how other species retain the ability to regenerate can help us to find solutions for improving our regenerative capacities. The zebrafish is an organism that is capable of regenerating multiple organs in its body. Using zebrafish as a model organism, previous studies have identified key processes and illustrated the crucial cell types and genes for regeneration. In caudal fin specifically, blastema formation is a key predictor of successful regeneration. However, a comprehensive molecular understanding of cell type-specific contributions to this process is lacking. In this dissertation, I present our efforts toward …

Testing Of A Novel Combined Eating-Disorder And Weight-Loss Online Guided-Self Help Intervention For Young Adults With A Binge-Type Eating Disorder And Overweight Or Obesity, Grace Elise Monterubio

Arts & Sciences Graduate Student Theses and Dissertations

Binge-type eating disorders (EDs) and obesity-related health concerns are two serious medical issues, though study of their treatment has largely remained separate. This study implemented an online, guided self-help ED intervention that concurrently offered Cognitive Behavioral Therapy (CBT)-based tools to improve ED symptoms, while also teaching energy-density food principles of behavioral weight loss (BWL), for individuals with clinical/sub-clinical binge-type EDs with comorbid overweight/obesity. The study aimed to examine change in weight, change in ED symptoms, and program engagement between a combined intervention (CBT + BWL) and an ED-only intervention. Participants in the combined intervention group received weekly session content pertaining …

Uneasy Attachments: Postcolonial Anglophilia And Identity Formation In Twentieth-Century Anglophone Autobiographies, Anwesha Kundu

Arts & Sciences Graduate Student Theses and Dissertations

This dissertation focuses on the impact of anglophilia on identity formation in the British empire. Since Britishness was an identity unavailable to non-white citizens of the empire, this attachment was necessarily unrequited. Analyzing works by Cornelia Sorabji, E.R. Braithwaite, V.S. Naipaul, and Tsitsi Dangarembga, I argue that the critical significance of anglophilia does not lie in the postcolonial subject’s success or failure in achieving a British-coded identity, but in the ways in which an affiliation to Britishness can be mobilized to accomplish a variety of personal, political, and social ends. I use a range of autobiographical literature—travel narratives, autobiographical novels, …

Extensive Behavioral Phenotyping Of Williams Syndrome Locus Relevant Mouse Models To Assess Contributions Of Oxytocin And Gtf2ird1, Kayla Rose Nygaard

Arts & Sciences Graduate Student Theses and Dissertations

The Williams Syndrome Critical Region (WSCR) at chromosome 7q11.23 provides a unique opportunity to untangle the relationship between genotype and phenotype in complex behaviors, from fear and anxiety to sociability and sensorimotor processing. Copy number variations (CNVs) in this region result in two syndromes, Williams Syndrome (WS) and Duplication 7q11.23 Syndrome (Dup7), which display phenotypes that may align, indicating a common disruption of a system, or diverge, reflecting an underlying gene dosage-dependent effect. While case studies of atypical deletions resulting in WS have implicated telomeric genes Gtf2ird1 and Gtf2i in the cognitive and behavioral profiles of WS, proving causation requires …

Characterizing Complex Affective Processing Across Age And In Relation To Social Anxiety Symptoms, M. Catalina Camacho

Arts & Sciences Graduate Student Theses and Dissertations

Humans require a shared understanding of others’ emotions for adaptive social functioning. For instance, if someone tells a joke and another person laughs, we assume the laughing person was happy because we have a shared concept for such positive interactions. Children develop and refine these concepts as they grow up, but the underlying neural processing that supports this development is unknown. Identifying the neurodevelopment underlying emotion processing could provide important insight to emotional disorders. For example, social anxiety is associated differences in the detection and interpretation of negative or neutral emotional cues, but the underlying neurodevelopment of this behavior is …

The Role Of The Neurodevelopmental Disorder Gene Myt1l In Mammalian Brain Development, Jiayang Chen

Arts & Sciences Graduate Student Theses and Dissertations

Recent human genetic studies have associated mutations in a gene called Myelin Transcription Factor 1 Like (MYT1L) with neurodevelopmental disorders (NDDs). Patients with MYT1L loss of function (LoF) mutations (MYT1L Syndrome patients) demonstrate shared symptoms such as microcephaly, attention deficit and hyperactivity disorder (ADHD), and obesity. Despite prior studies showing MYT1L overexpression facilitates neuronal differentiation in vitro, its functions in vivo, especially in the mammalian brain, and how its mutation leads to human disease pathology remains poorly understood. Here, I established the first mouse model of MYT1L Syndrome mimicking a patient specific LoF mutation. I found mice with Myt1l heterozygous …

Connections Between Mechanosensitive Ion Channel Msl10 And Er-Plasma Membrane Contact Sites, Jennette Marie Codjoe

Arts & Sciences Graduate Student Theses and Dissertations

Mechanosensitive (MS) ion channels are an evolutionarily conserved way for cells to sense mechanical forces and transduce them into ionic signals. A plasma membrane-localized MS channel from Arabidopsis thaliana, MscS-Like (MSL)10, senses cell swelling and initiates a signaling cascade that triggers programmed cell death. Whereas the channel properties of MSL10 have been well studied, how MSL10 signals remains largely unknown. I worked collaboratively to show that important lesions for cell death signaling in the cytosolic N- and C-terminal domains of MSL10 interact genetically. I also helped show that ionic flux through MSL10 is dispensable for signaling, which suggested that MSL10 …

Circadian Circuitry And Glioblastoma: Interactions With Behavior, Carcinogenesis, And Clinical Practice., Anna R. Damato

Arts & Sciences Graduate Student Theses and Dissertations

Glioblastoma (GBM) is the most common primary adult brain tumor diagnosed, with a 15-month prognosis using current standard of care treatment which includes chemotherapy with temozolomide (Temodar, TMZ). Chronotherapy, the practice of considering time of day in treating a disease, has been shown to improve outcome in several cancers, but had not been applied to GBM. Previous work in the lab on a cultured murine mesenchymal GBM cell line showed a time-of-day dependent maximum in sensitivity to TMZ corresponding with the daily peak of Bmal1 and trough of Per2 expression, two core clock genes. Based on this finding, we sought …

Development Of Redox-Responsive Phenazine-Based Foldamers. Acylative Kinetic Resolution Of Hydroxamic Acids, Jingwei Yin

Arts & Sciences Graduate Student Theses and Dissertations

Two different research directions have been presented in this thesis. The first project is about phenazine-based foldamers as molecular actuators. Researchers have been interested in the design and synthesis of foldamers and molecular actuators for years. We began our exploration by demonstrating that phenazine-1,6-dicarboxamides can function as redox-responsive molecular switches. We then designed and synthesized two generations of phenazine-based interleafed foldamers and studied their stability and redox behaviors under chemical and electrochemical conditions. In the second project, we have developed the first acylative kinetic resolution on hydroxamic acids. Although chiral hydroxamic acids have extensive applications, synthetic methods towards them are …

Functional Analysis Of Recurrent Non-Coding Variants In Human Melanoma, Paula Maria Godoy

Arts & Sciences Graduate Student Theses and Dissertations

Worldwide incidence rates of cutaneous melanoma are increasing, and while survival rates for early stages of melanoma are high, rates drop precipitously for metastatic melanomas or those that are unable to be targeted by currently available treatments. As melanomas have a propensity to quickly metastasize, understanding the contributions of melanoma initiation remains critical for early intervention. Onset of melanoma is characterized most by mutations that stimulate mitogen-activated protein kinase (MAPK) signaling, disrupt DNA damage checkpoints, and trigger mechanisms to bypass senescence through elongation of telomeres. Additionally, in zebrafish melanoma models, the earliest cluster of melanoma-initiating cells activate expression of a …

Reassessing The History Of The Poverty Point Phenomenon: A Case Study From The Jaketown Site, Mississippi, Usa, Seth Bradley Grooms

Arts & Sciences Graduate Student Theses and Dissertations

Towards the end of the Late Archaic period (ca. 4800-3000 cal BP), between 3,600 and 3,300 years ago, Native Americans engineered a colossal earthwork complex that covers approximately 200 hectares in northeast Louisiana. Today, it is a UNESCO World Heritage site known as Poverty Point and the namesake for a material culture pattern documented to varying degrees at sites throughout the Lower Mississippi Valley (LMV). However, the nature of interactions between these sites and the type site is poorly understood. The people who constructed the Poverty Point site lived on wild food resources. They hunted, fished, and gathered food from …

Host Development And Microbiota Influences On Norovirus Infection, Elizabeth Alexandra Kennedy

Arts & Sciences Graduate Student Theses and Dissertations

The mammalian gut is a complex organ which changes over the course of development and is influenced by the presence of a dense community of gut-resident microbes. Enteric viruses infect the gastrointestinal tract in the context of the commensal microbiota and host immunity. Here, we dissect the influence of host developmental stage and the gut microbiota in norovirus infection. From this work, we determine that murine norovirus (MNoV) infection in early life is restricted by an absence of the target MNoV cell tuft cells and intact interferon (IFN) signaling. However, viral inoculum taken up by non-specific endocytosis in the neonatal …

Effects Of Surface Ligation On Charge Extraction From Wurtzite Cadmium Selenide Quantum Platelets And Quantum Belts, Hailey Meyer

Arts & Sciences Graduate Student Theses and Dissertations

This dissertation presents the synthesis of flat, colloidal wurtzite CdSe quantum platelets and quantum belts for ligand exchange to novel and existing organic and inorganic L-, X-, and Z- type ligands. Use of these ligands in conjunction with the semiconductor nanocrystals allows for examination of their ligand exchange abilities, photoluminescence quenching efficiencies, and charge transfer properties.First, zinc and cadmium dithiocarbamate compounds [M(S2CNR1R2)2] are used as ligands on wurtzite CdSe quantum belts. Complete ligand exchange is achieved when the belts are initially ligated with Cd(oleate)2, a Z-type ligand, prior to the exchange, as opposed to n-octylamine or ammonia, which are both …

Essays On Macroeconomics And Finance, Matias Nicolas Marzani

Arts & Sciences Graduate Student Theses and Dissertations

This dissertation investigates the relationship between risk and finance at the level of firms. In the first chapter, a model is developed in which optimal debt maturity is determined by a balance between the higher rollover risk of short-term debt and the higher risk-taking incentives of long-term debt. Evidence is provided using firm-level data on sales growth volatility and resource allocation to business lines. The second chapter explores the role of financial innovation in securities issuance, finding that the introduction of new financial products improves a firm's ability to raise funds. A model of the allocation of financial products among …

Functionalized Plasmonic Nanostructures For Ultrasensitive Single Cell Analysis, Priya Rathi

Arts & Sciences Graduate Student Theses and Dissertations

Ultrasensitive detection and quantification of soluble, secreted and cell surface-bound proteins is critical for advancing our understanding of cellular systems, enabling effective drug development, novel therapies, and bio-diagnostics. However, exiting technologies are largely limited by their sensitivity, making the detection and quantification of low-abundant proteins extremely challenging. This forms a major barrier in various fields of biology and biomedical sciences. In this work, we introduce novel cellular analysis methodologies based on plasmon-enhanced fluorescence for analyzing cell structure and probing surface and secreted proteins from cells. In the first part, we introduce plasmon-enhanced expansion microscopy and demonstrate the effectiveness of employing …

Modernism As Public Art: Reawakening The Social Agency Of Abstract Public Sculpture, 1950–1980, Tola Porter

Arts & Sciences Graduate Student Theses and Dissertations

This dissertation presents a critical reassessment of postwar modern public sculpture and offers a framework for both the reevaluation and reawakening of these significant, inherited public images. Between 1950 and 1980, as a result of new national policies, the United Kingdom and the United States experienced a boom in public sculpture. That phenomenon was augmented by architectural modernism, whose stark buildings called for the addition of sculpture. The growing prestige of abstract art made it a popular choice for architects and commissioners, who sought to leverage the cachet of contemporary artists. For both private sector architects and public sector patrons, …

Genetic And Transcriptomic Aspects Of Major Depressive Disorder: In Vivo Functional Assays Of Risk-Associated Variation, Candidate Disease Cell Types, And Their Pharmacologic And Sex Interactions, Bernard Mulvey

Arts & Sciences Graduate Student Theses and Dissertations

Major depressive disorder (MDD) is a debilitating illness that affects hundreds of millions globally, with substantial personal, medical, economic, and societal consequences. While depression occurs more commonly in females, the biology of the brain and sex underlying this skewed prevalence remains unclarified. This body of work explores two aspects of how biological sex may influence the brain at the level of gene expression: through intrinsic sex differences and through sex-mediated effects of depression risk genetics.The monoamine hypothesis of depression suggests that modulatory neurotransmitters including serotonin and norepinephrine constitute a key axis in development of MDD. Large-scale studies of MDD treatment …

Roles Of Behavioral Novelty And Organismal Energetics In The Evolution Of Extreme Encephalization, Erika Laurie Schumacher

Arts & Sciences Graduate Student Theses and Dissertations

Brains and their component brain regions vary widely in size and structure across vertebrates. However, extreme increases in total brain size relative to body size (extreme encephalization) and increases in specific major brain region sizes independent of other brain regions (mosaic brain evolution) are relatively rare. There are several hypotheses as to why, but the energetic cost of increased brain tissue and the regional interconnectedness in both brain development and function likely constrain how brains are able to change in response to selection. In this dissertation, I sought to address both how behavioral novelty relates to evolutionary changes in brain …