Life Sciences Commons^™

Pesticides As Multiple Stressors To Bivalves And Echinoderms, Alexandra Gabrielle Tissot

Dissertations and Theses

Pesticides are ubiquitous in aquatic environments, alongside numerous contaminants and other stressors that can result in combined exposure to target and non-target organisms. Nevertheless, traditional toxicity studies quantify the effects of these compounds at an individual level, and to a narrow range of traditional test organisms. Through this dissertation, I explored the presence and effects of commonly detected pesticides of concern in the Pacific Northwest in order to realistically quantify potential effects from combined stressors. In Chapter 2, I demonstrated my background knowledge on these select pesticides (atrazine, bifenthrin, diuron, indaziflam, and imidacloprid), including their chemical and physical properties. Using …

Mulberry Leaf Disease Detection By Cnn-Vit With Xai Integration, Mohammad Asif Hasan, Fariha Haque, Hasan Sarker, Rafae Abdullah, Tonmoy Roy, Nishat Taaha, Yeasin Arafat, Abdul Karim Patwary, Mominul Ahsan, Julfikar Haider

Instructional Technology and Learning Sciences Faculty Publications

Mulberry leaf disease detection is vital for maintaining the health and productivity of mulberry crops. In this paper, a novel approach was proposed by integrating explainable artificial intelligence (XAI) techniques with a convolutional neural network (CNN) and vision transformer (ViT) for effective mulberry leaf disease classification with three disease classes. Initially, in this proposed CNN-ViT model, features are extracted using a customized CNN architecture, and then the extracted features are fed into ViT for leaf disease classification in a more streamlined approach. The CNN-ViT model achieved promising results with a projection dimension of 64, utilizing 8 heads and 8 transformer …

Kaiso Mediates Transcription And Rna Splicing In Colorectal Carcinoma: Role Of Brca1 In The Kaiso Enhanceosome, Weifeng Luo, Manish Kumar Tripathi, Qi Liu, Lei Chen, Robert W. Cowan, Juliet M. Daniel, Chi Yan, Ann Richmond, Albert B. Reynolds

School of Medicine Publications

Kaiso (ZBTB33) is a transcription factor involved in mitotic clonal expansion and tumorigenesis in association with Adenomatous Polyposis Coli (APC) loss of heterozygosity. ENCODE data show strong overlap of the Kaiso promoter-binding site—encode-derived Kaiso-binding site (eKBS) and many other transcription factors, including BRCA1. Here we sought to determine whether BRCA1 is a component of the Kaiso enhanceosome that regulates gene transcription. Using proximal ligation assays, immunoprecipitation followed by mass spectrometry, luciferase assays and ChIP-seq experiments, we evaluated the association between BRCA1 and Kaiso. Kaiso nuclear extract immunoprecipitation experiments revealed that Kaiso associates strongly with genes involved in RNA splicing and …

Nebraska National Agri-Marketing Association (Nama), Marissa Davis, Rosalee A. Swartz

Cornhusker Economics

NAMA PALOOZA, the 2025 Agri-Marketing Conference, was held April 9-11 in Kansas City, Missouri. The conference is an annual event that brings together National Agri-Marketing Association (NAMA) professional and student members. There are 27 professional chapters and 32 student chapters from across the United States and Canada. The conference is a great opportunity to foster connections between students and professionals in marketing, advertising, communications, promotion, sales, and public relations.

Eph Receptors Activate Myeloid Checkpoint Receptor Lilrb5 To Support Tumor Development, Yubo He, Chengcheng Zhang, Lingxiao Tan, Mi Deng, Xiaoye Liu, Ryan Huang, Xing Yang, Jingjing Xie, Qi Lou, Meng Fang, Caroline Smith, Samuel John, Wei Xiong, Xin Li, Cheryl Lewis, Jade Homsi, Ankit Gupta, Ningyan Zhang, Zhiqiang An, Cheng Cheng Zhang

Faculty, Staff and Student Publications

Immunosuppressive myeloid cells are critical obstacles to T cell-centered immune checkpoint blockade therapies, which have been successful in treating a fraction of patients with cancer. How tumor cells interact with myeloid cells to regulate immune responses and tumor development is unclear. In this study, we report that certain membrane tyrosine kinase Eph receptors, including EphA7 and EphB1, specifically bind the immune inhibitory receptors leukocyte Ig-like receptor family B 5 (LILRB5) and LILRB2. These Eph receptors induce LILRB5-mediated signaling activation, and LILRB5 also activates Eph receptor signaling. Activation of LILRB5 promoted immunosuppressive marker expression and inhibited activating marker expression on myeloid …

Deep Learning Based Rapid X-Ray Fluorescence Signal Extraction And Image Reconstruction For Preclinical Benchtop X-Ray Fluorescence Computed Tomography Applications, Amrit Kaphle, Sandun Jayarathna, Sang Hyun Cho

Faculty, Staff and Student Publications

Recent research advances have resulted in an experimental benchtop X-ray fluorescence computed tomography (XFCT) system that likely meets the imaging dose/scan time constraints for benchtop XFCT imaging of live mice injected with gold nanoparticles (GNPs). For routine in vivo benchtop XFCT imaging, however, additional challenges, most notably the need for rapid/near-real-time handling of X-ray fluorescence (XRF) signal extraction and XFCT image reconstruction, must be successfully addressed. Here we propose a novel end-to-end deep learning (DL) framework that integrates a one-dimensional convolutional neural network (1D CNN) for rapid XRF signal extraction with a U-Net model for XFCT image reconstruction. We trained …

Deep Learning Based Rapid X-Ray Fluorescence Signal Extraction And Image Reconstruction For Preclinical Benchtop X-Ray Fluorescence Computed Tomography Applications, Amrit Kaphle, Sandun Jayarathna, Sang Hyun Cho

Faculty, Staff and Student Publications

Recent research advances have resulted in an experimental benchtop X-ray fluorescence computed tomography (XFCT) system that likely meets the imaging dose/scan time constraints for benchtop XFCT imaging of live mice injected with gold nanoparticles (GNPs). For routine in vivo benchtop XFCT imaging, however, additional challenges, most notably the need for rapid/near-real-time handling of X-ray fluorescence (XRF) signal extraction and XFCT image reconstruction, must be successfully addressed. Here we propose a novel end-to-end deep learning (DL) framework that integrates a one-dimensional convolutional neural network (1D CNN) for rapid XRF signal extraction with a U-Net model for XFCT image reconstruction. We trained …

Olaparib And Radiotherapy Induce Type I Interferon- And Cd8+ T Cell-Dependent Sensitization To Immunotherapy In Pancreatic Cancer, Victoria M Valvo, Qiang Zhang, Long Jiang, Erin A Holcomb, Ashley N Pearson, Anna G Edmunds, Hailey G Faulkner, Jadyn G James, Akshay Tate, Amanda K Huber, Zhuwen Wang, Yupei Guo, David Karnak, Leslie A Parsels, Joshua D Parsels, Yu L Lei, Alnawaz Rehemtulla, Heng Lin, Eileen S Carpenter, Daniel R Wahl, Vaibhav Sahai, Theodore S Lawrence, Michael D Green, Meredith A Morgan

Faculty, Staff and Student Publications

PARP inhibitors sensitize pancreatic ductal adenocarcinoma (PDAC) to radiation by inducing DNA damage and replication stress. These mechanisms also have the potential to enhance radiation-induced type I interferon (T1IFN) mediated anti-tumoral immune responses. We hypothesized that the PARP inhibitor olaparib would also potentiate radiation-induced T1IFN to promote anti-tumor immune responses and sensitization of otherwise resistant PDAC to immunotherapy. To test this hypothesis, we assessed the effects of olaparib and radiation on T1IFN production and sensitivity to αPD-L1 immunotherapy, as well as on the tumor microenvironment by single-cell RNA sequencing (scRNA-seq). We found that olaparib enhanced T1IFN production following radiation and …

Lmp7-Specific Inhibitor M3258 Modulates The Tumor Microenvironment Of Triple-Negative Breast Cancer And Inflammatory Breast Cancer, Xuemei Xie, Jangsoon Lee, Ganiraju C Manyam, Troy Pearson, Gina Walter-Bausch, Manja Friese-Hamim, Sheng Zhao, Julia Jabs, Angela A Manginelli, Nadine Piske, Thomas Mrowiec, Corinna M Wolf, Bharat S Kuntal, Debu Tripathy, Jing Wang, Michael P Sanderson, Naoto T Ueno

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) and inflammatory breast cancer (IBC) are the most aggressive molecular subtypes of breast cancer. Poor clinical outcomes highlight the pressing need to discover novel targets for the effective treatment of these diseases. LMP7 (β5i/PSMB8), a proteolytic subunit of the immunoproteasome, is implicated in the pathogenesis of multiple myeloma, autoimmune and inflammatory diseases, and inflammation-related cancers. However, the role of LMP7 in TNBC and IBC remains poorly characterized. Here, we evaluated the function of LMP7 in TNBC and IBC using the selective LMP7 inhibitor M3258. In human TNBC patient samples, LMP7 expression correlated strongly with CD8+ T …

Mesenchymal Stem Cells And Fibroblasts Contribute To Microvascular Proliferation In Glioblastoma And Are Correlated With Immunosuppression And Poor Outcome, Candice C Poon, Shelley M Herbrich, Yulong Chen, Anwar Hossain, Gregory N Fuller, Sonali Jindal, Sreyashi Basu, Daniel Ledbetter, Marc Macaluso, Lynnette M Phillips, Joy Gumin, Zhong He, Brittany C Parker Kerrigan, Sanjay K Singh, Pratishtha Singh, Mohammed Fayyad Zaman, Derek Ng Tang, Sangeeta Goswami, Frederick F Lang, Padmanee Sharma

Faculty, Staff and Student Publications

Microvascular proliferation (MVP) is a disease-defining hallmark of glioblastoma and other World Health Organization grade 4 gliomas. MVP also serves as a poor prognostic marker in various solid tumors. Despite its clinical significance, the mechanisms and biological consequences of MVP are controversial and remain unclear. In this study, we performed single-cell RNA sequencing on paired CD45-CD105+ vascular/perivascular stromal cells (PVSC) and CD45+CD105± immune cells from 16 primary glioma patient samples, both with and without MVP. This analysis revealed the presence of developmentally related mesenchymal stem cells alongside cancer-associated fibroblasts, pericytes, fibromyocytes, and smooth muscle cells within the CD45-CD105+ compartment. RNA …

The Present And Future Of Precision Oncology And Tumor-Agnostic Therapeutic Approaches, Nakul M Shah, Funda Meric-Bernstam

Faculty, Staff and Student Publications

Precision oncology has transformed the treatment landscape for patients with advanced solid tumors. Tumor-agnostic therapies, those that have been approved based on genetic mutations or biomarkers across tumor histology types, are important examples of how the implementation of precision oncology can expand therapeutic options for patients, especially those with rare cancer types and treatment-refractory disease. In this review, we first discuss how advances in next-generation sequencing and molecular profiling have enabled the identification of shared actionable alterations. Subsequently, we explore the current landscape of tumor-agnostic therapies that have received approval from the Food and Drug Administration. We discuss the strengths …

Nitrate And Nitrite Levels In Cattle Feed, Drinking Water, Rumen Content, And Blood Methemoglobin Levels In Burdur Province Of Türkiye, Reyda Kiyici, Hasan Altan Akkan, Mehmet Karaca, Esra Zeybek, Bayram Kudret Karaayvaz, Fi̇rdevs Mor Savaş, Yahya Öztürk, Asim Kart, Ramazan Yildiz, Murat Bayezi̇t

Turkish Journal of Veterinary & Animal Sciences

This study was conducted to determine the risk factors associated with nitrate/nitrite poisoning in cattle in the Burdur region. Feed and water samples were collected from 10 different farms randomly selected from 9 districts. A total of 33 feed samples, 13 water samples, 21 rumen contents, and 20 blood samples were collected for analysis. Nitrate and nitrite levels in feed, drinking water, and rumen fluid, as well as methemoglobin levels in blood samples, were determined using a spectrophotometric method. The average nitrate and nitrite levels in feed samples were 3.06 mg/kg and 3.54 mg/kg, respectively. The mean nitrate and nitrite …

Effect Of In-Season Potentiation And Priming On Jump Height In Collegiate D1 American Football Players, Benjamin Dagostino, Kody Cooke, Paulette Yamada, Trevor Short

Topics in Exercise Science and Kinesiology

Neuromuscular priming and post-activation potentiation (PAP) are techniques utilized to increase nervous system excitation, muscle force, and rate of force development during subsequent muscle contractions in sport. PAP is a commonly used approach that has the potential to influence neuromuscular status monitoring and flagging, and optimize power training. Specifically, jump height is an important parameter in athletic performance and assessing inter-limb asymmetries. Thus, the purpose of this paper is to report the effects of different PAP strategies on jump height during a competitive D1 American football season. These findings will inform practitioners on optimal PAP strategies and their implications …

Unravelling Host Defense And Pathogen Virulence In Fusarium Proliferatum-Induced Sudden Decline Syndrome Of Date Palm In The Uae, Gouthaman Puthan Purayil

Thesis/ Dissertation Defenses

Sudden decline syndrome (SDS) poses a significant threat to the date palm (Phoenix dactylifera), a crop of critical agricultural and cultural importance in arid regions. Despite its growing impact, the molecular basis of the host-pathogen interactions driving this disease remains poorly understood. This dissertation investigates the disease dynamics of SDS, a severe affliction of date palm caused by the fungal pathogen Fusarium proliferatum DSM 106835 (Fp). The objective of this study is to elucidate the molecular mechanisms underlying Fp infection in date palm and characterize the plant defense responses. To achieve this, whole-genome sequencing (WGS) of the novel Fp strain …

The Effect Of Family Communication On Adolescent Sexual Behaviors And Attitudes, Jonathan Young

Family Perspectives

Unhealthy sexual behaviors among adolescents, such as engaging with multiple partners or neglecting contraceptive use, can lead to significant physical, psychological, and relational consequences. This literature review explores the influence of family communication on adolescent sexual behaviors and attitudes, emphasizing the role of parent-adolescent discussions in promoting healthier sexual practices and reshaping sexual values. Research indicates that open, reciprocal family communication is associated with reduced sexual risk-taking, fewer sexual partners, delayed sexual debut, and increased contraceptive use. Moreover, conversations centered on positive sexual norms, such as love and respect, facilitate adolescents’ adoption of healthier sexual values. Effective family communication also …

Detecting Physical Activity Using Wearable Sensor Data, Dipok Deb

Data Science and Data Mining

This study focuses on detecting physical activity using wearable sensor data, specifically distinguishing between walking and running. A dataset comprising accelerometer and gyroscope readings is used to train and evaluate various machine learning models, including logistic regression, random forest, k-nearest neighbors, naïve Bayes, and XGBoost. Extensive preprocessing, such as creating lag features and rolling statistics, is performed to enhance temporal data representation. The models are evaluated using metrics like accuracy, precision, recall, and F1 score. Incorporating lag and rolling features significantly improves model performance, with logistic regression achieving perfect scores across all metrics. These findings demonstrate the effectiveness of enhanced …

Proceedings From The Sixth Annual Society For Sports Neuroscience Conference, Neurosports Editorial Staff

Journal for Sports Neuroscience

Proceedings from the Sixth Annual Society for Sports Neuroscience Conference

Co-Designing A Digital Nutrition Intervention For Individuals With Severe Mental Illness Using The Behaviour Change Wheel, Ciara O'Sullivan, Tara Coppinger, Indika Dhanapala, Alison Merrotsy

Publications

Title: Co-Designing a Digital Nutrition Intervention for Individuals with Severe Mental Illness Using the Behaviour Change Wheel

Purpose: This study aims to develop a digital nutrition intervention for individuals with severe mental illness (SMI) residing in high-support mental health hostels, using a theoretically informed co-design approach.

Design/methodology/approach: This study will employ a participatory, mixed-methods approach, incorporating Public and Patient Involvement (PPI) to ensure user-centred intervention design. The Behaviour Change Wheel (BCW) guides the selection of intervention functions, Behaviour Change Techniques (BCTs) and delivery methods. The study will consist of three phases: (1) Preparation, (2) Co-Design, and (3) Finalisation.

Findings: Data …

Atp8b1 Regulates Pip2 Localization And Cleavage Of Pyroptotic Executioner Gasdermin D, Nilam Bhandari, Ashutosh Prince, Mariam R. Khan, Alicia Traughbera, Kalash Neupane, Shuhui W. Lorkowski, Gregory Brubaker, Elif G. Ertugral, Chandrasekhar R. Kothapalli

Chemical & Biomedical Engineering Faculty Publications

Mutations in ATP8B1 cause progressive familial intrahepatic cholestasis, with symptoms including pruritus, pancreatitis, fat malabsorption, intestinal inflammation, and failure to thrive. High-throughput studies showed interconnection between ATP8B1 and phosphoinositide (PIPs), but the mechanism linking ATP8B1, lipid metabolism, and inflammation remains unclear. Atp8b1G308V/G308V mouse model, unbiased RNAseq, high-resolution-stimulation emission depltion (STED)-microscopy, and Crispr-Cas9 generated ATP8B1-/- knockouts in hepatocytes/monocytes/macrophages were used to determine role of ATP8B1 in phosphatidylinositol,4-5-bisphosphate (PIP2) trafficking and inflammation. Human ATP8B1, purified from Sf9 insect cells and reconstituted in proteoliposomes, was used to test cell-free PIP2 flip. Various in-vitro techniques were used for testing direct interaction between PIP2 and …

Creation Of An Open Access Textbook, Sue Ann Gardner

University of Nebraska-Lincoln Libraries: Presentations

Slide presented during the PRCA Research Celebration, June 3, 2025, in the University Libraries, University of Nebraska-Lincoln titled Creation of an Open Access Textbook, about the development and publication of Concepts in Animal Parasitology, co-edited by Scott L. Gardner and Sue Ann Gardner and published by Zea Books (Lincoln, Nebraska, USA) in 2024.

Suggested Vegetable Planting Dates For Utah, Shawn Olsen

All Current Publications

This fact sheet provides suggested planting dates for vegetables in various areas throughout Utah. It also identifies resources for starting seeds at home.

Phage-Induced Protection Against Lethal Bacterial Reinfection, Yikun Xing, Haroldo J Hernandez Santos, Ling Qiu, Samantha R Ritter, Jacob J Zulk, Rachel Lahowetz, Kathryn A Patras, Austen L Terwilliger, Anthony W Maresso

Faculty, Staff and Students Publications

Bacteriophages, or phages, are viruses that target and infect bacteria. Due to a worldwide rise in antimicrobial resistance (AMR), phages have been proposed as a promising alternative to antibiotics for the treatment of resistant bacterial infections. Up to this point in history, phage use in preclinical animal studies, clinical trials, and emergency-use compassionate care cases has centered around the original observation from 1915 showing phage as lytic agent, and thus a treatment that kills bacteria. Here, we describe an activity associated with phage therapy that extends beyond lytic activity that results in long-term protection against reinfection. This activity is potent, …

Culture Harder: Use More Specimen To Increase Methicillin-Resistant Staphylococcus Aureus Culture Yield Relative To Pcr, Arvette E. Mitchell, Arpit P. Patel, Jennifer Dicandilo, Zachary W. Rebollido, Matthew Pettengill

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Methicillin-resistant Staphylococcus aureus (MRSA) causes considerable morbidity and mortality in both community-acquired and healthcare-associated infections, but detecting colonization with MRSA has been shown to improve patient outcomes in certain clinical settings. MRSA colonization detection has been carried out in a variety of ways, with molecular assays having superior sensitivity in most studies relative to culture, but culture is disadvantaged in some comparisons by utilization of low specimen volumes. We compared a commercial molecular assay to both low-volume (10 µl) and high-volume (650 µl) cultures and found that increasing the volume utilized for culture led to the detection of 25% more …

Posterior Predictive Design For Phase I Clinical Trials, Chenqi Fu, Shouhao Zhou, J Jack Lee

Faculty, Staff and Student Publications

Interval-based designs represent cutting-edge adaptive methodologies for phase I clinical trials to identify the maximum tolerated dose (MTD). These designs exhibit robust performance comparable to more intricate, model-based designs, and their pretabulated decision rule enables them to be implemented as simply as the conventional algorithm-based designs. In this paper, we introduce the posterior predictive (PoP) design, a novel interval-based design that leverages advanced Bayesian predictive hypothesis testing techniques for dose escalation and de-escalation. Our work moves beyond the existing model-assisted interval-based designs by achieving global optimality in dose transition. Theoretically, the global optimality ensures that the proposed design can consistently …

Plasma Insulin-Like Growth Factor-Binding Protein-7 Is Positively Associated With Age, Obesity, Mortality, And Cancer In Postmenopausal Women, Melissa C Orenduff, Carl F Pieper, Emma H Allott, Michael F Coleman, Su Yon Jung, Mara Z Vitolins, Jenifer I Fenton, Chu Chen, Candyce H Kroenke, Fred K Tabung, Ana Barac, Electra D Paskett, Michael N Pollak, Jennifer Hays-Grudo, Shine Chang, Stephen D Hursting

Faculty, Staff and Student Publications

Background: Predictors of premature death and cancer development are needed to more precisely identify individuals who may warrant preventive intervention. Circulating insulin-like growth factor (IGF)-binding protein-7 (IGFBP7) and, to a lesser extent, the IGFBP7/IGF-1 ratio are emerging biomarkers of renal and cardiovascular morbidity. However, their relationships with aging, obesity, mortality, and cancer risk remain unclear.

Methods: This hypothesis-generating study investigated plasma IGFBP7, IGF-1, and their ratio as predictors of all-cause mortality and the incidence of any cancer (excluding nonmelanoma skin cancer), obesity-related cancer (composite of 13 cancer types), and breast cancer in a large longitudinal cohort of postmenopausal women. We …

Mutant P53 Gain Of Function: Why Many See It, Why Some Do Not, Guillermina Lozano, Carol Prives, Kanaga Sabapathy

Faculty, Staff and Student Publications

Mutations in the TP53 tumor-suppressor gene in human cancer are unique in that 60% to 70% are of the missense variety, resulting in a full-length protein that is often highly expressed in patients' tumors. These missense mutant proteins often exhibit pro-oncogenic activities (referred to as gain of function) in mouse models and human cell lines and correlate with poor cancer prognosis in some cases.

Restoration Of The Tumor Suppressor Function Of Y220c-Mutant P53 By Rezatapopt, A Small-Molecule Reactivator, Anna M Puzio-Kuter, Lizhong Xu, Mary Kate Mcbrayer, Romyr Dominique, Hongju H Li, Bruce J Fahr, Alyssa M Brown, Amy E Wiebesiek, Brandon M Russo, Chris L Mulligan, Hong Yang, Josh Battaglia, Kimberly A Robell, Dafydd H Thomas, Kuo-Sen Huang, Alexander Solovyov, Benjamin D Greenbaum, Jonathan D Oliner, Thomas W Davis, Melissa L Dumble, Melissa L Johnson, Shunbin Xiong, Peirong Yang, Guillermina Lozano, Marc M Fellous, Binh T Vu, Alison M Schram, Arnold J Levine, Masha V Poyurovsky

Faculty, Staff and Student Publications

Restoration of the tumor suppressor function of tumor-associated p53 mutants, including the Y220C substitution, has posed a significant challenge for therapeutic discovery. In this study, we describe rezatapopt (PC14586), part of a series of compounds designed to reactivate the p53 Y220C mutant. These compounds restore p53 tumor suppressor function by correcting its conformation and enabling it to bind DNA and activate downstream target genes, thus inducing antiproliferative changes in tumor cells. Our findings are supported by biochemical and structural analysis, in vitro and in vivo transcriptomics, and functional data, revealing the recovery of multiple aspects of the wild-type p53 program. …

Genetic And Biochemical Analyses Reveal Litr's Role In Vibrio Fischeri Biofilm Formation, Brittany Loi Fung

Dissertations

Quorum sensing controls numerous processes ranging from production of virulence factors to biofilm formation. Biofilms, communities of bacteria that are attached to one another and/or a surface, are common in nature and, when they form, can produce a quorum of bacteria. One model system to study biofilms is the bacterium Vibrio fischeri, which forms a biofilm that promotes colonization of its symbiotic host. Many factors promote V. fischeri biofilm formation in vitro, including the symbiosis polysaccharide (SYP), cellulose, and the LapV adhesin but, so far, only a handful of studies have probed connections between biofilm formation and quorum sensing. In …

Pyruvate Dehydrogenase Kinase 4 Mediates Sex Specific Outcomes In Sepsis Induced Cardiomyopathy, John Yap

Dissertations

During sepsis, males often experience worse cardiac outcomes than females. Here, we identified pyruvate dehydrogenase kinase 4 (PDK4) as a key contributor to this disparity. PDK4 is a mitochondrial protein that regulates glucose utilization by inhibiting pyruvate dehydrogenase (PDH). Using a mouse model of endotoxemia, we induced acute inflammation with a sublethal dose of lipopolysaccharide (LPS), which caused cardiac dysfunction and significantly increased myocardial PDK4 expression in males but not females. Cardiac-specific PDK4 overexpression promoted LPS-induced cardiac dysfunction in both sexes, whereas cardiac-specific PDK4 knockout provided protection. In wild-type males, LPS disrupted cardiac metabolism by decreasing PDH activity and fatty …

Investigating The Consequences Of Conjugated And Secreted Isg15 On Coronavirus Pathogenesis, Mudassir Syed Ali

Dissertations

Coronaviruses have evolved a breadth of mechanisms to antagonize host innate immune responses. One widely studied mechanism is the ability to deconjugate ISG15 from target proteins in a process called deISGylation, which is catalyzed by the papain-like protease (PLP) domain of viral non-structural protein (nsp) 3. Since PLP activity is required for viral replication, it has been challenging to generate an infectious virus with a PLP that maintains protease activity but has lost deISGylase activity. In this study, we generated a chimeric MHV-A59 with its PLP2 domain replaced with that of the human coronavirus HKU1, which has been documented to …