Digital Commons Network^™

The Initial Age-Associated Decline In Early T-Cell Progenitors Reflects Fewer Pre-Thymic Progenitors And Altered Signals In The Bone Marrow And Thymus Microenvironments, Jayashree Srinivasan, Anusha Vasudev, Carolyn Shasha, Hilary J Selden, Encarnacion Perez, Bonnie Lafleur, Shripad A Sinari, Andreas Krueger, Ellen R Richie, Lauren I R Ehrlich

Faculty, Staff and Student Publications

Age-related thymus involution results in decreased T-cell production, contributing to increased susceptibility to pathogens and reduced vaccine responsiveness. Elucidating mechanisms underlying thymus involution will inform strategies to restore thymopoiesis with age. The thymus is colonized by circulating bone marrow (BM)-derived thymus seeding progenitors (TSPs) that differentiate into early T-cell progenitors (ETPs). We find that ETP cellularity declines as early as 3 months (3MO) of age in mice. This initial ETP reduction could reflect changes in thymic stromal niches and/or pre-thymic progenitors. Using a multicongenic progenitor transfer approach, we demonstrate that the number of functional TSP/ETP niches does not diminish with …

Clinical, Endoscopic, And Histopathologic Gastrointestinal Disease In An American Cohort With Behçet's Disease, Bryan F Curtin, Kareen L Hill, Sumona Bhattacharya, Astin Powers, Aradhana Venkatesan, Preet Bagi, Elizabeth Joyal, Meghna Alimchandani, Raphaela Goldbach-Mansky, Peter Grayson, Martha Quezado, Cailin Sibley, Theo Heller

Faculty, Staff and Student Publications

INTRODUCTION: Behçet's disease (BD) is a chronic systemic vasculitis characterized by oral and genital ulcers, uveitis, and skin lesions. Patients with BD may develop gastrointestinal (GI) disease; however, characterization of GI disease in American cohorts is lacking. In this article, we present clinical, endoscopic, and histopathologic GI findings in an American cohort of patients with BD.

METHODS: Patients with established BD were evaluated prospectively at the National Institutes of Health. Demographic and clinical data were collected including BD manifestations and GI symptoms. Endoscopy with histopathologic sampling was performed for both clinical and research indications with written consent.

RESULTS: Eighty-three patients …

Short-Course Therapy For Urinary Tract Infections In Children: The Scout Randomized Clinical Trial, Theoklis Zaoutis, Nader Shaikh, Brian T Fisher, Susan E Coffin, Sonika Bhatnagar, Kevin J Downes, Jeffrey S Gerber, Timothy R Shope, Judith M Martin, Gysella B Muniz, Michael Green, Jennifer P Nagg, Sage R Myers, Rakesh D Mistry, Shawn O'Connor, Walter Faig, Stephen Black, Elizabeth Rowley, Kellie Liston, Alejandro Hoberman

Faculty, Staff and Student Publications

IMPORTANCE: There is a paucity of pediatric-specific comparative data to guide duration of therapy recommendations in children with urinary tract infection (UTI).

OBJECTIVE: To compare the efficacy of standard-course and short-course therapy for children with UTI.

DESIGN, SETTING, PARTICIPANTS: The Short Course Therapy for Urinary Tract Infections (SCOUT) randomized clinical noninferiority trial took place at outpatient clinics and emergency departments at 2 children's hospitals from May 2012, through, August 2019. Data were analyzed from January 2020, through, February 2023. Participants included children aged 2 months to 10 years with UTI exhibiting clinical improvement after 5 days of antimicrobials.

INTERVENTION: Another …

The Hylefm Gene In Phylefm Of Enterococcus Faecium Is Not Required In Pathogenesis Of Murine Peritonitis, Victoria H Wu, Bryan S Yung, Farhoud Faraji, Robert Saddawi-Konefka, Zhiyong Wang, Alexander T Wenzel, Miranda J Song, Meghana S Pagadala, Lauren M Clubb, Joshua Chiou, Sanju Sinha, Marin Matic, Francesco Raimondi, Thomas S Hoang, Rebecca Berdeaux, Dario A A Vignali, Ramiro Iglesias-Bartolome, Hannah Carter, Eytan Ruppin, Jill P Mesirov, J Silvio Gutkind

Faculty, Staff and Student Publications

Immune checkpoint blockade (ICB) targeting PD-1 and CTLA-4 has revolutionized cancer treatment. However, many cancers do not respond to ICB, prompting the search for additional strategies to achieve durable responses. G-protein-coupled receptors (GPCRs) are the most intensively studied drug targets but are underexplored in immuno-oncology. Here, we cross-integrated large singe-cell RNA-sequencing datasets from CD8+ T cells covering 19 distinct cancer types and identified an enrichment of Gαs-coupled GPCRs on exhausted CD8+ T cells. These include EP2, EP4, A2AR, β1AR and β2AR, all of which promote T cell dysfunction. We also developed transgenic mice expressing a chemogenetic CD8-restricted Gαs–DREADD to activate …

Understanding The Environmental And Genetic Influence On Fluctuating Asymmetry And Developmental Instability In Primates, Ashly N. Romero

Graduate Theses and Dissertations

This dissertation explored the impact of environmental factors on the development and perpetuation of fluctuating asymmetry (FA) and sought to understand the role evolution may play in the FA exhibited in two primate populations: the free-ranging Cayo Santiago rhesus macaques (Macaca mulatta) and the Southwest National Primate Research Center olive baboons (Papio hamadryas anubis). Demographic, ontogenetic, secular, external, and genetic factors were examined. Specifically, this dissertation investigated FA over all ontogenetic stages, across decades, between sexes, in association with ecological catastrophes, and with tooth pathology to try and tease apart factors that may influence FA and developmental instability. This dissertation …

Do Vaccinations Influence The Development Of Alzheimer Disease?, Avram S Bukhbinder, Yaobin Ling, Kristofer Harris, Xiaoqian Jiang, Paul E Schulz

Faculty, Staff and Student Publications

A growing literature supports a protective association between vaccines targeting an array of pathogens (e.g., influenza, pneumococcus, herpes zoster) and the risk of Alzheimer disease (AD). This article discusses the potential underlying mechanisms for this apparent protective effect of immunizations against infectious pathogens on the risk of AD; explores the basic and pharmacoepidemiologic evidence for this association, with particular attention paid to important methodological variations among the epidemiologic studies; and reviews the remaining uncertainties regarding the effects of anti-pathogen vaccines on Alzheimer disease and all-cause dementia, with recommendations for future directions to address those uncertainties.

Barriers And Determinants Of Consistent Offering Of Hpv Vaccination By Healthcare Facilities, Ikponmwosa Osaghae, Onyema Greg Chido-Amajuoyi, Banda A A Khalifa, Sanjay Shete

Faculty, Staff and Student Publications

Expanding access to HPV vaccination is critical to increasing HPV vaccine uptake. We assessed the determinants and barriers to consistent offering of HPV vaccine among healthcare facilities. This was a cross-sectional survey of healthcare providers (HCPs) in Texas. Prevalence of the reasons healthcare practices do not consistently offer HPV vaccination was estimated. Multivariable regression analyses were conducted. Of 1169 HCPs included in the study, 47.5% (95% CI: 44.6-50.3%) reported their practices do not provide HPV vaccination or do not offer it consistently. Compared to physicians, nurses had 77% lower odds (Adjusted Odds Ratio (AOR): 0.23, 95% CI: 0.16-0.32, p-value: < .001), and physician assistants had 89% lower odds (AOR: 0.11, 95% CI: 0.07-0.16, p-value: < .001) of their healthcare practices consistently offering HPV vaccination. Compared to university/teaching hospitals, the odds of healthcare practices consistently offering HPV vaccination were 44% lower (AOR: 0.56, 95% CI: 0.35-0.91, p-value: 0.019) in solo practices but 266% higher (AOR: 3.66, 95% CI: 2.04-6.58, p-value: < .001) in FQHC/public facilities. The common reasons healthcare practices do not consistently offer HPV vaccination were; HPV vaccination is not within the scope of the practice (48.1%), referrals to other clinics (27.7%), and limited personnel (11.4%). Non-physicians were more likely to report that HPV vaccination was not in their scope and to refer patients than physicians. Moreover, solo practices were more likely to report challenges with acquisition and storage of the vaccine and referral of patients as reasons for not consistently offering HPV vaccination than university/teaching hospitals, FQHC/public facilities, or group practices. System-level interventions including training of non-physicians and expansion of practice enrollment in programs that support HPV vaccine acquisition and storage are needed.

Nivolumab And Ipilimumab In Combination With Radiotherapy In Patients With High-Risk Locally Advanced Squamous Cell Carcinoma Of The Head And Neck., Jennifer Johnson, Ioannis A. Vathiotis, Larry Harshyne, Ayesha Ali, Voichita Bar-Ad, Rita S. Axelrod, Emily Lorber, Joseph Curry, David Cognetti, Adam J. Luginbuhl, Madalina Tuluc, Scott W Keith, M.G. Mahoney, Athanassios Argiris

Department of Medical Oncology Faculty Papers

BACKGROUND: The combination of nivolumab and ipilimumab has been approved for the treatment of multiple solid tumors. This was a phase I study investigating definitive radioimmunotherapy (RIT) with nivolumab and ipilimumab for the treatment of locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN).

METHODS: Patients with newly diagnosed, stage IVA-IVB SCCHN eligible for cisplatin-based chemotherapy received nivolumab (3 mg/kg every 2 weeks for a total of 17 doses) and ipilimumab (1 mg/kg every 6 weeks for a total of 6 doses) starting 2 weeks prior to radiotherapy. The primary endpoint was safety of definitive RIT. Secondary …

Illuminating Underappreciated Mechanisms Of Receptor Regulation In Human Lymphocytes., Cassandra Woolley

Electronic Theses and Dissertations

A thorough understanding of receptor regulation is imperative to predict expression in varying contexts of disease or treatment. Lymphocyte surface receptors are often used as biomarkers and drug targets, making them particularly important for study. For receptors of debated functionality, such as the Fc receptor for IgM (FcMR), understanding regulation can also help to predict expression in vivo to supplement hypotheses of biological roles. Various mechanisms exist for altering receptor surface expression, including direct feedback mechanisms such as ligand-induced endocytosis and broader mechanisms such as transcriptional and translational control. In this dissertation, we explore selected underappreciated mechanisms of lymphocyte receptor …

New Species Of Dryolestoid From The Late Cretaceous Allen Formation And Implications For South American Faunal Diversity., Brigid Erin Connelly

Electronic Theses and Dissertations

Dryolestoids are extinct cladotherians mammals from the Jurassic and Cretaceous periods. I describe a collection of dryolestoid specimens from the Late Cretaceous localities of Cerro Tortuga (Allen Formation), Anfiteatro 1, and Shining (both La Colonia Formation) from Patagonia, Argentina. Using comparative morphology, I identify a new species of meridiolestidan dryolestoid based on eleven specimens across both formations. The new species’ recovery from La Colonia Formation represents the first dryolestoid connection between the two approximately contemporaneous formations. The species’ morphology may represent an ecological shift within Meridiolestida from insectivory to herbivory, showing a transition in characters between the plesiomorphic sharp-toothed meridiolestidans …

Investigating The Effects Of E219 Mutations In M. Tuberculosis Indole-3-Glycerol Phosphate Synthase, Cinthya Moran

Theses, Dissertations and Culminating Projects

Tuberculosis (TB) is a serious infectious disease caused by Mycobacterium tuberculosis. Tuberculosis drug resistance is increasingly a problem, but recent research has provided results that suggest Indole-3-Glycerol Phosphate Synthase (IGPS) could be a potential drug target. IGPS is an enzyme that catalyzes the fourth step in the tryptophan biosynthesis pathway, a crucial process for optimal Mycobacterium tuberculosis growth. In this research, we studied IGPS from Mycobacterium tuberculosis (MtIGPS) to shed light on a particular conserved residue that has not been studied in depth in any IGPS homolog. My investigation focuses on understanding the role of the active site residue E219. …

Leveraging Eco-Evolutionary Models For Gene Drive Risk Assessment, Matthew A. Combs, Andrew J. Golnar, Justin M. Overcash, Alun L. Lloyd, Keith R. Hayes, David A. O'Brochta, Kim M. Pepin

United States Department of Agriculture Wildlife Services: Staff Publications

Engineered gene drives create potential for both widespread benefits and irreversible harms to ecosystems. CRISPR-based systems of allelic conversion have rapidly accelerated gene drive research across diverse taxa, putting field trials and their necessary risk assessments on the horizon. Dynamic processbased models provide flexible quantitative platforms to predict gene drive outcomes in the context of system-specific ecological and evolutionary features. Here, we synthesize gene drive dynamic modeling studies to highlight research trends, knowledge gaps, and emergent principles, organized around their genetic, demographic, spatial, environmental, and implementation features. We identify the phenomena that most significantly influence model predictions, discuss limitations of …

Knowledge Representation And Management 2022: Findings In Ontology Development And Applications, Jean Charlet, Licong Cui, Section Editors For The Imia Yearbook Section On Knowledge Representation And Management

Faculty, Staff and Student Publications

OBJECTIVES: To select, present, and summarize the best papers in 2022 for the Knowledge Representation and Management (KRM) section of the International Medical Informatics Association (IMIA) Yearbook.

METHODS: We conducted PubMed queries and followed the IMIA Yearbook guidelines for performing biomedical informatics literature review to select the best papers in KRM published in 2022.

RESULTS: We retrieved 1,847 publications from PubMed. We nominated 15 candidate best papers, and two of them were finally selected as the best papers in the KRM section. The topics covered by the candidate papers include ontology and knowledge graph creation, ontology applications, ontology quality assurance, …

Dengue Outbreak Response During Covid-19 Pandemic, Key Largo, Florida, Usa, 2020, Devin Rowe, Catherine Mcdermott, Ysla Veliz, Alison Kerr, Mark Whiteside, Mikki Coss, Chad Huff, Andrea Leal, Edgar Kopp, Alexis Lacrue, Lea A Heberlein, Laura E Adams, Gilberto A Santiago, Jorge L Munoz-Jordan, Gabriela Paz-Bailey, Andrea M Morrison

Faculty, Staff and Student Publications

We report a dengue outbreak in Key Largo, Florida, USA, from February through August 2020, during the COVID-19 pandemic. Successful community engagement resulted in 61% of case-patients self-reporting. We also describe COVID-19 pandemic effects on the dengue outbreak investigation and the need to increase clinician awareness of dengue testing recommendations.

Structural Study Of Lsd13 And Lsd14 Type I Modular Polyketide Synthases From The Lasalocid A Biosynthesis Pathway, Dayan Viera

Open Access Theses & Dissertations

Bioactive natural products often possess a complex structure and have a large size which make their chemical synthesis highly challenging. To overcome this challenge, we are developing a biosynthetic method for production of natural products and their analogs. This technology is expected to decrease the synthesis time from years to weeks and reduce the cost of drug production by multiple orders of magnitude. We are investigating the biosynthesis pathway of lasalocid A, an anticancer antibiotic, to develop this technology. Specifically, we aim to characterize the enzymes structurally and biochemically in this pathway, thus paving the way for their rational engineering. …

Inhibition Of Microsomal Prostaglandin E2 Synthase Reduces Collagen Deposition In Melanoma Tumors And May Improve Immunotherapy Efficacy By Reducing T-Cell Exhaustion, Yasunari Fukuda, Sun-Hee Kim, Matias A Bustos, Sung-Nam Cho, Jason Roszik, Jared K Burks, Hong Kim, Dave S B Hoon, Elizabeth A Grimm, Suhendan Ekmekcioglu

Faculty, Staff and Student Publications

The arachidonic acid pathway participates in immunosuppression in various types of cancer. Our previous observation detailed that microsomal prostaglandin E2 synthase 1 (mPGES-1), an enzyme downstream of cyclooxygenase 2 (COX-2), limited antitumor immunity in melanoma; in addition, genetic depletion of mPGES-1 specifically enhanced immune checkpoint blockade therapy. The current study set out to distinguish the roles of mPGES-1 from those of COX-2 in tumor immunity and determine the potential of mPGES-1 inhibitors for reinforcing immunotherapy in melanoma. Genetic deletion of mPGES-1 showed different profiles of prostaglandin metabolites from that of COX-2 deletion. In our syngeneic mouse model, mPGES-1-deficient cells exhibited …

Foreword From Handling Editor - 10th Edition, Ahyahudin Sodri

Journal of Environmental Science and Sustainable Development

We are delighted to present the 10th edition of JESSD, published in July 2023. We have selected twelve of the best articles for this edition that related with topic of Environmental Science and Sustainable Development.

Distribution Of The Soft Tick Carios Vespertilionis In Lowlands And Low Mountain Regions Of Germany, Anja Fritzsche, Stefan Zaenker, Jannis Gottwald, Renate Keil, Christian Zaenker, Michael Bröker, Lidia Chitimia-Dobler

Harold W. Manter Laboratory of Parasitology: Library Materials

In Germany, the knowledge about ticks infesting bats is limited, and is restricted only to a few studies, most of them dating back decades. To further improve our knowledge on ticks parasitising bats, healthy and sick bats in central Germany were examined for ticks. In total 519 larvae and one nymph of Carios vespertilionis were collected from nine bat species: Eptesicus nilssonii, Eptesicus serotinus, Myotis daubentonii, Myotis myotis, Nyctalus leisleri, Pipistrellus nathusii, Pipistrellus pygmaeus, Pipistrellus pipistrellus, and Vespertilio murinus. Either the presence of C. vespertilionis was new for some areas or it was confirmed in some federal states in …

A Phase Ii Clinical Trial Of Pembrolizumab Efficacy And Safety In Advanced Renal Medullary Carcinoma, Chijioke Nze, Pavlos Msaouel, Mohamed H Derbala, Bettzy Stephen, Abdulrahman Abonofal, Funda Meric-Bernstam, Nizar M Tannir, Aung Naing

Faculty, Staff and Student Publications

Background: Renal medullary carcinoma (RMC) is one of most aggressive renal cell carcinomas and novel therapeutic strategies are therefore needed. Recent comprehensive molecular and immune profiling of RMC tissues revealed a highly inflamed phenotype, suggesting the potential therapeutic role for immune checkpoint therapies. We present the first prospective evaluation of an immune checkpoint inhibitor in a cohort of patients with RMC.

Methods: A cohort of patients with locally advanced or metastatic RMC was treated with pembrolizumab 200 mg intravenously every 21 days in a phase II basket trial (ClinicalTrials.gov: NCT02721732). Responses were assessed by irRECIST. Tumor tissues were evaluated …

Investigating The Physiological Mechanisms Between Resistance Training And Pain Relief In The Cancer Population: A Literature Review, Yvonne Jiang, Peter C. Angeletti, Amy J. Hoffman

Nebraska Center for Virology: Faculty Publications

This literature review examines the mechanisms of how exercise, specifically in the form of resistance training, may lead to pain relief in the cancer population. Primary data from three different cancer populations: breast, prostate, and lung, will be examined. A number of experimental studies have been conducted to confirm the effectiveness of resistance training on pain relief as well as the biochemical pathways that relate to this process. In this review, we will examine 5 randomized controlled trials. For the purposes of this review, pain is defined as physical suffering or discomfort associated with illness. Pain is the body’s natural …

Islet: Individual-Specific Reference Panel Recovery Improves Cell-Type-Specific Inference, Hao Feng, Guanqun Meng, Tong Lin, Hemang Parikh, Yue Pan, Ziyi Li, Jeffrey Krischer, Qian Li

Faculty, Staff and Student Publications

We propose a statistical framework ISLET to infer individual-specific and cell-type-specific transcriptome reference panels. ISLET models the repeatedly measured bulk gene expression data, to optimize the usage of shared information within each subject. ISLET is the first available method to achieve individual-specific reference estimation in repeated samples. Using simulation studies, we show outstanding performance of ISLET in the reference estimation and downstream cell-type-specific differentially expressed genes testing. We apply ISLET to longitudinal transcriptomes profiled from blood samples in a large observational study of young children and confirm the cell-type-specific gene signatures for pancreatic islet autoantibody. ISLET is available at https://bioconductor.org/packages/ISLET …

Comprehensive Analysis Of The Prognostic Significance Of The Trim Family In The Context Of Tp53 Mutations In Cancers, Trung Vu, Annaliese Fowler, Nami Mccarty

Faculty, Staff and Student Publications

The p53 protein is an important tumor suppressor, and TP53 mutations are frequently associated with poor prognosis in various cancers. Mutations in TP53 result in a loss of p53 function and enhanced expression of cell cycle genes, contributing to the development and progression of cancer. Meanwhile, several tripartite motif (TRIM) proteins are known to regulate cell growth and cell cycle transition. However, the prognostic values between TP53 and TRIM family genes in cancer are unknown. In this study, we analyzed the relationship between the

Tissue-Specific Features Of The T Cell Repertoire After Allogeneic Hematopoietic Cell Transplantation In Human And Mouse, Susan Dewolf, Yuval Elhanati, Katherine Nichols, Nicholas R Waters, Chi L Nguyen, John B Slingerland, Natasia Rodriguez, Olga Lyudovyk, Paul A Giardina, Anastasia I Kousa, Hana Andrlová, Nick Ceglia, Teng Fei, Rajya Kappagantula, Yanyun Li, Nathan Aleynick, Priscilla Baez, Rajmohan Murali, Akimasa Hayashi, Nicole Lee, Brianna Gipson, Madhumitha Rangesa, Zoe Katsamakis, Anqi Dai, Amanda G Blouin, Maria Arcila, Ignas Masilionis, Ronan Chaligne, Doris M Ponce, Heather J Landau, Ioannis Politikos, Roni Tamari, Alan M Hanash, Robert R Jenq, Sergio A Giralt, Kate A Markey, Yanming Zhang, Miguel-Angel Perales, Nicholas D Socci, Benjamin D Greenbaum, Christine A Iacobuzio-Donahue, Travis J Hollmann, Marcel R M Van Den Brink, Jonathan U Peled

Faculty, Staff and Student Publications

T cells are the central drivers of many inflammatory diseases, but the repertoire of tissue-resident T cells at sites of pathology in human organs remains poorly understood. We examined the site-specificity of T cell receptor (TCR) repertoires across tissues (5 to 18 tissues per patient) in prospectively collected autopsies of patients with and without graft-versus-host disease (GVHD), a potentially lethal tissue-targeting complication of allogeneic hematopoietic cell transplantation, and in mouse models of GVHD. Anatomic similarity between tissues was a key determinant of TCR repertoire composition within patients, independent of disease or transplant status. The T cells recovered from peripheral blood …

Harnessing Autoimmunity With Dominant Self-Peptide: Modulating The Sustainability Of Tissue-Preferential Antigen-Specific Tregs By Governing The Binding Stability Via Peptide Flanking Residues, Youwei Lin, Shun Sakuraba, Chandirasegaran Massilamany, Jayagopala Reddy, Yoshimasa Tanaka, Sachiko Miyake, Takashi Yamamura

School of Veterinary and Biomedical Sciences: Faculty Publications

Sensitization to self-peptides induces various immunological responses, from autoimmunity to tumor immunity, depending on the peptide sequence; however, the underlying mechanisms remain unclear, and thus, curative therapeutic options considering immunity balance are limited. Herein, two overlapping dominant peptides of myelin proteolipid protein, PLP136-150 and PLP139-151, which induce different forms of experimental autoimmune encephalomyelitis (EAE), monophasic and relapsing EAE, respectively, were investigated. Mice with monophasic EAE exhibited highly resistant to EAE re-induction with any encephalitogenic peptides, whereas mice with relapsing EAE were susceptible, and progressed, to EAE re-induction. This resistance to relapse and reinduction in monophasic EAE mice was associated with …

Preclinical Evaluation Of Anti-Cd38 Therapy In Mature T-Cell Neoplasms, Colleen Isabelle, William Johnson, Kathleen Mcconnell, Ashley Vogel, Jonathan Brammer, Amy Boles, Robyn Keller, Paola Sindaco, Liam Nisenfeld, Guldeep Uppal, Neda Nikbakht, Bruno Calabretta, Patrizia Porazzi, Jerald Gong, Nitin Chakravarti, Pierluigi Porcu, Anjali Mishra

Kimmel Cancer Center Faculty Papers

No abstract provided.

Role Of Short Interspersed Nuclear Elements (Sines) Of Maternally Imprinted Microrna Clusters In Hemochorial Placental Antiviral Immunity, Ishani Wickramage

USF Tampa Graduate Theses and Dissertations

The evolution of hemochorial placentas in which the fetal trophoblast is bathed in maternal blood has vastly improved fetal development and survival in primates and rodents, due to the enhanced efficiency of nutrient, gas and waste exchange between the mother and the fetus. However, the extensive contact between the fetal tissues and maternal blood in these placentas also poses an increased risk of vertical transmission of pathogens such as viruses from the mother to the fetus. In response to this selection pressure, hemochorial placentas have evolved robust defense mechanisms to protect the immunologically naive fetus. Unlike somatic cells that require …

The Knowns And Unknowns Of Cardiac Autoimmunity In Viral Myocarditis, Kiruthiga Mone, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Myocarditis can result from various infectious and non‐infectious causes that can lead to dilated cardiomyopathy (DCM) and heart failure. Among the infectious causes, viruses are commonly suspected. But the challenge is our inability to demonstrate infectious viral particles during clinical presentations, partly because by that point, the viruses would have damaged the tissues and be cleared by the immune system. Therefore, viral signatures such as viral nucleic acids and virus-reactive antibodies may be the only readouts pointing to viruses as potential primary triggers of DCM. Thus, it becomes hard to explain persistent inflammatory infiltrates that might occur in individuals affected …

Sars‑Cov‑2 Entry Into And Evolution Within A Skilled Nursing Facility, Nicole R. Sexton, Parker Parker Cline, Emily N. Gallichotte, Emily Fitzmeyer, Michael C. Young, Ashley J. Janich, Kristy L. Pabilonia, Nicole Ehrhart, Gregory D. Ebel

Nebraska Center for Virology: Faculty Publications

SARS-CoV-2 belongs to the family Coronaviridae which includes multiple human pathogens that have an outsized impact on aging populations. As a novel human pathogen, SARS-CoV-2 is undergoing continuous adaptation to this new host species and there is evidence of this throughout the scientific and public literature. However, most investigations of SARS-CoV-2 evolution have focused on largescale collections of data across diverse populations and/or living environments. Here we investigate SARS-CoV-2 evolution in epidemiologically linked individuals within a single outbreak at a skilled nursing facility beginning with initial introduction of the pathogen. The data demonstrate that SARSCoV- 2 was introduced to the …

Proteomic Approaches To Identify Unique And Shared Substrates Among Kinase Family Members, Charles Lincoln Howarth

Dartmouth College Ph.D Dissertations

Protein phosphorylation is a reversible post-translational modification that is a critical component of almost all signaling pathways. Kinases regulate substrate proteins through phosphorylation, and nearly all proteins are phosphorylated to some extent. Crucially, breakdown in phosphorylation signaling is an underlying factor in many diseases, including cancer. Understanding how phosphorylation signaling mediates cellular pathways is crucial for understanding cell biology and human disease.

Targeted protein degradation (TPD) is a strategy to rapidly deplete a protein of interest (POI) and is applicable to any gene that is amenable to CRISPR-Cas9 editing. One TPD approach is the auxin-inducible degron (AID) system, which relies …

The Effect Of Sodium Bicarbonate On Acute Kidney Injury Markers During Physical Work In The Heat, Abdulaziz Abdulrahman A. Masoud, Fabiano Amorim, Christine Mermier, Michael Deyhle, Zidong Li

Health, Exercise, and Sports Sciences ETDs

Sodium bicarbonate supplementation (NaHCO₃) before physical work in the heat may reduce the risk of developing acute kidney injury (AKI). Purpose: To determine the effects of NaHCO₃ supplementation before a prolonged bout of physical work in the heat on AKI markers and kidney function. Method: A randomized, cross-over, double blinded design was conducted on 8 participants (3 females) who consumed NaHCO₃ (0.2 g/kg body weight) or placebo (CON) before prolonged (120 minutes) moderate intensity (~65% of maximal heart rate) physical work in the heat [40℃ and 23% relative humidity (RH)]. Blood and urine samples were collected …