Biological Phenomena, Cell Phenomena, and Immunity Commons^™

The Fgfr1 Signaling Pathway Upregulates The Oncogenic Transcription Factor Foxq1 To Promote Breast Cancer Cell Growth, Yan Lin, Fengkang Lin, Zhuoran Zhang, Lijia Peng, Wenli Yang, Mao Yang, Bo Luo, Ting Wu, Dabing Li, Xuesen Li, Bing Ran, Songyot Anuchapreeda, Rujirek Chaiwongsa, Pinyaphat Khamphikham, Suwit Duangmano, Jianming Xu, Tao He, Sakorn Pornprasert

Faculty, Staff and Students Publications

FGFR1 is a receptor tyrosine kinase deregulated in certain breast cancers (BCs) with a poor prognosis. Although FGFR1-activated phosphorylation cascades have been mapped, the key genes regulated by FGFR1 in BC are largely unclear. FOXQ1 is an oncogenic transcription factor. Although we found that activation of FGFR1 robustly upregulated FOXQ1 mRNA, how FGFR1 regulates FOXQ1 gene expression and whether FOXQ1 is essential for FGFR1-stimulated cell proliferation are unknown. Herein, we confirmed that activation of FGFR1 robustly upregulated FOXQ1 mRNA and protein in BC cells. Knockdown of FOXQ1 blocked the FGFR1 signaling-stimulated BC cell proliferation, colony formation, and xenograft tumor growth. …

Sphingolipids In Neurodegenerative Diseases, Xueyang Pan, Debdeep Dutta, Shenzhao Lu, Hugo J Bellen

Faculty, Staff and Students Publications

Neurodegenerative Diseases (NDDs) are a group of disorders that cause progressive deficits of neuronal function. Recent evidence argues that sphingolipid metabolism is affected in a surprisingly broad set of NDDs. These include some lysosomal storage diseases (LSDs), hereditary sensory and autonomous neuropathy (HSAN), hereditary spastic paraplegia (HSP), infantile neuroaxonal dystrophy (INAD), Friedreich’s ataxia (FRDA), as well as some forms of amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD). Many of these diseases have been modeled in Drosophila melanogaster and are associated with elevated levels of ceramides. Similar changes have also been reported in vertebrate cells and mouse models. Here, we …

Chromosomal Microarray Analysis Supplements Exome Sequencing To Diagnose Children With Suspected Inborn Errors Of Immunity, Breanna J Beers, Morgan N Similuk, Rajarshi Ghosh, Bryce A Seifert, Leila Jamal, Michael Kamen, Michael R Setzer, Colleen Jodarski, Rylee Duncan, Devin Hunt, Madison Mixer, Wenjia Cao, Weimin Bi, Daniel Veltri, Eric Karlins, Lingwen Zhang, Zhiwen Li, Andrew J Oler, Kathleen Jevtich, Yunting Yu, Haley Hullfish, Bibiana Bielekova, Pamela Frischmeyer-Guerrerio, An Dang Do, Laryssa A Huryn, Kenneth N Olivier, Helen C Su, Jonathan J Lyons, Christa S Zerbe, V Koneti Rao, Michael D Keller, Alexandra F Freeman, Steven M Holland, Luis M Franco, Magdalena A Walkiewicz, Jia Yan

Faculty, Staff and Students Publications

PURPOSE: Though copy number variants (CNVs) have been suggested to play a significant role in inborn errors of immunity (IEI), the precise nature of this role remains largely unexplored. We sought to determine the diagnostic contribution of CNVs using genome-wide chromosomal microarray analysis (CMA) in children with IEI.

METHODS: We performed exome sequencing (ES) and CMA for 332 unrelated pediatric probands referred for evaluation of IEI. The analysis included primary, secondary, and incidental findings.

RESULTS: Of the 332 probands, 134 (40.4%) received molecular diagnoses. Of these, 116/134 (86.6%) were diagnosed by ES alone. An additional 15/134 (11.2%) were diagnosed by …

Squamous Cell Carcinoma With Unusual Benign-Appearing Cystic Features On Histology, Usman Asad, Suzanne Alkul, Ikue Shimizu, Jennifer Ranario

Faculty, Staff and Students Publications

Squamous cell carcinoma (SCC) is a malignancy that arises from keratinocytes of the epidermis. Cystic variants of several types of cutaneous neoplasms have been rarely described in the literature. We report a case of biopsy-proven, well-differentiated invasive SCC treated with Mohs surgery. On frozen sections, the pathology slides showed benign-appearing cystic structures in the margins that persisted after it had appeared that the original malignancy had been cleared. After taking another Mohs stage due to clinical suspicion, additional SCC was found and was subsequently cleared after two more Mohs stages. To the best of our knowledge, this is the first …

Novel Banana Lectin Car-T Cells To Target Pancreatic Tumors And Tumor-Associated Stroma, Mary K Mckenna, Ada Ozcan, Daniel Brenner, Norihiro Watanabe, Maureen Legendre, Dafydd G Thomas, Christopher Ashwood, Richard D Cummings, Challice Bonifant, David M Markovitz, Malcolm K Brenner

Faculty, Staff and Students Publications

BACKGROUND: Cell therapies for solid tumors are thwarted by the hostile tumor microenvironment (TME) and by heterogeneous expression of tumor target antigens. We address both limitations with a novel class of chimeric antigen receptors based on plant lectins, which recognize the aberrant sugar residues that are a 'hallmark' of both malignant and associated stromal cells. We have expressed in T cells a modified lectin from banana, H84T BanLec, attached to a chimeric antigen receptor (H84T-CAR) that recognizes high-mannose (asparagine residue with five to nine mannoses). Here, we tested the efficacy of our novel H84T CAR in models of pancreatic ductal …

Variantsurvival: A Tool To Identify Genotype-Treatment Response, Thomas Krannich, Marina Herrera Sarrias, Hiba Ben Aribi, Moustafa Shokrof, Alfredo Iacoangeli, Ammar Al-Chalabi, Fritz J Sedlazeck, Ben Busby, Ahmad Al Khleifat

Faculty, Staff and Students Publications

Associated Data

The Covert Symphony: Cellular And Molecular Accomplices In Breast Cancer Metastasis, Hongjiang Si, Madelyn Esquivel, Erika Mendoza Mendoza, Kevin Roarty

Faculty, Staff and Students Publications

Breast cancer has emerged as the most commonly diagnosed cancer and primary cause of cancer-related deaths among women worldwide. Although significant progress has been made in targeting the primary tumor, the effectiveness of systemic treatments to prevent metastasis remains limited. Metastatic disease continues to be the predominant factor leading to fatality in the majority of breast cancer patients. The existence of a prolonged latency period between initial treatment and eventual recurrence in certain patients indicates that tumors can both adapt to and interact with the systemic environment of the host, facilitating and sustaining the progression of the disease. In order …

Figure-8-Reconstruction Of Posterior Sternoclavicular Joint Dislocation 18 Days Post Initial Injury, M Suri, S Bunemann

Clinical Practice in Athletic Training

Introduction: Traumatic sternoclavicular joint injuries account for less than 3% of all traumatic joint injuries1. Although rare, posterior dislocation of the sternoclavicular joint has the potential to be life-threatening due to the proximity of vital structures posterior to the manubrium. This injury typically requires a high-energy force applied through the joint2. SC dislocations become increasingly difficult to reduce after 24 hours, so timely diagnosis and treatment are important. Glass et al. found mediastinal compression occurred 30% of the time with posterior dislocations. If left untreated, prolonged pressure on the superior mediastinum can cause erosion of the great vessels, tracheoesophageal fistula, …

Acute Liver Failure And Unique Challenges Of Pediatric Liver Transplantation Amidst A Worldwide Cluster Of Adenovirus-Associated Hepatitis, Anna M Banc-Husu, Elizabeth A Moulton, Henry Shiau, Luz Helena Gutierrez Sanchez, Moreshwar S Desai, Dana Cerminara, Flor M Munoz, Leanne M Buffaloe, Kristen G Valencia-Deray, N Thao N Galvan, Julu Bhatnagar, Lindsey Estetter, Negar Rassaei, Sarah Reagan-Steiner, Jason Wicker, James J Dunn, Carl E Allen, Kalyani R Patel, Sanjiv Harpavat, John A Goss, Daniel H Leung

Faculty, Staff and Students Publications

Investigation into a recent cluster of acute hepatitis in children from the southeastern United States identified human adenovirus (HAdV) DNAemia in all 9 cases. Molecular genotyping in 5 of 9 (56%) children identified HAdV type 41 in all cases (100%). Importantly, 2 children from this cluster progressed rapidly to pediatric acute liver failure (PALF) and required liver transplantation. HAdV type 41, a known cause of self-limited gastroenteritis, has not previously been associated with severe cholestatic hepatitis and liver failure in healthy children. Adenovirus polymerase chain reaction assay and sequencing of amplicons performed on DNA extracted from formalin-fixed, paraffin-embedded liver tissue …

Cell-Type-Specific Aging Clocks To Quantify Aging And Rejuvenation In Neurogenic Regions Of The Brain, Matthew T Buckley, Eric D Sun, Benson M George, Ling Liu, Nicholas Schaum, Lucy Xu, Jaime M Reyes, Margaret A Goodell, Irving L Weissman, Tony Wyss-Coray, Thomas A Rando, Anne Brunet

Faculty, Staff and Students Publications

The diversity of cell types is a challenge for quantifying aging and its reversal. Here we develop 'aging clocks' based on single-cell transcriptomics to characterize cell-type-specific aging and rejuvenation. We generated single-cell transcriptomes from the subventricular zone neurogenic region of 28 mice, tiling ages from young to old. We trained single-cell-based regression models to predict chronological age and biological age (neural stem cell proliferation capacity). These aging clocks are generalizable to independent cohorts of mice, other regions of the brains, and other species. To determine if these aging clocks could quantify transcriptomic rejuvenation, we generated single-cell transcriptomic datasets of neurogenic …

Circulating Tumor Dna Sequencing Of Pediatric Solid And Brain Tumor Patients: An Institutional Feasibility Study, Ross Mangum, Jacquelyn Reuther, Koel Sen Baksi, Ilavarasi Gandhi, Ryan C Zabriskie, Alva Recinos, Robin Raesz-Martinez, Frank Y Lin, Samara L Potter, Andrew C Sher, Stephen F Kralik, Carrie A Mohila, Murali M Chintagumpala, Donna Muzny, Jianhong Hu, Richard A Gibbs, Kevin E Fisher, Juan Carlos Bernini, Jonathan Gill, Timothy C Griffin, Gail E Tomlinson, Kelly L Vallance, Sharon E Plon, Angshumoy Roy, D Williams Parsons

Faculty, Staff and Students Publications

The potential of circulating tumor DNA (ctDNA) analysis to serve as a real-time "liquid biopsy" for children with central nervous system (CNS) and non-CNS solid tumors remains to be fully elucidated. We conducted a study to investigate the feasibility and potential clinical utility of ctDNA sequencing in pediatric patients enrolled on an institutional clinical genomics trial. A total of 240 patients had tumor DNA profiling performed during the study period. Plasma samples were collected at study enrollment from 217 patients and then longitudinally from a subset of patients. Successful cell-free DNA extraction and quantification occurred in 216 of 217 (99.5%) …

Emergency Department Presentations Of Diabetic Ketoacidosis In A Large Cohort Of Children, Lise E Nigrovic, Nathan Kuppermann, Simona Ghetti, Jeff E Schunk, Michael J Stoner, Arleta Rewers, Julie K Mcmanemy, Kimberly S Quayle, Jennifer L Trainor, Leah Tzimenatos, Jonathan E Bennett, Maria Y Kwok, Sage R Myers, Kathleen M Brown, T Charles Casper, Cody S Olsen, Nicole S Glaser

Faculty, Staff and Students Publications

Background: Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of childhood diabetes. However, the influence of demographic factors on presentation are not well-defined.

Methods: We included children from 12 centers who were < 18 years with DKA (glucose > 300 mg/dL, serum pH < 7.25, or serum bicarbonate < 15 mEq/L) enrolled in the Pediatric Emergency Care Applied Research Network (PECARN) Fluid Therapies Under Investigation in DKA (FLUID) Trial. Data were also collected for children who presented to the centers during the enrollment period but were not enrolled due to disease or treatment-related reasons. We compared demographic, clinical, and biochemical findings among children with newly and previously diagnosed diabetes and children in different age groups.

Results: Of the 1,679 DKA episodes in 1,553 children, 799 (47.5%) episodes occurred in children with newly diagnosed diabetes and 396 (23.6%) were severe (pH < 7.1). Newly diagnosed children < 6 years of age were not more likely to have severe DKA in terms of pH, but had more severe hypocarbia and higher blood urea nitrogen levels, factors previously associated with the risk of cerebral injury. Lower socioeconomic status (SES) (based on family income and maternal education level) were associated with more severe DKA in new onset children, and recurrent DKA in the previously diagnosed children.

Conclusions: Greater efforts are needed to identify the children with diabetes early and to prevent recurrent DKA, particularly among children in low-SES groups. Young children with DKA may need more intensive monitoring due to higher risk of cerebral injury.

Binary Classification Of The Endocrine Disrupting Chemicals By Artificial Neural Networks, Zahir Aghayev, George F Walker, Funda Iseri, Moustafa Ali, Adam T Szafran, Fabio Stossi, Michael A Mancini, Efstratios N Pistikopoulos, Burcu Beykal

Faculty, Staff and Students Publications

We develop a machine learning framework that integrates high content/high throughput image analysis and artificial neural networks (ANNs) to model the separation between chemical compounds based on their estrogenic receptor activity. Natural and man-made chemicals have the potential to disrupt the endocrine system by interfering with hormone actions in people and wildlife. Although numerous studies have revealed new knowledge on the mechanism through which these compounds interfere with various hormone receptors, it is still a very challenging task to comprehensively evaluate the endocrine disrupting potential of all existing chemicals and their mixtures by pure

Editorial: Hemostasis In Ecmo And Vad, Volume Ii, Jun Teruya, Jean M Connors, Barbara Zieger

Faculty, Staff and Students Publications

No abstract provided.

Glial Cell-Specific Contribution Of Pkr-Like Er Kinase (Perk) In Neuroinflammation And Behavior, Anirudhya Lahiri

Graduate Theses, Dissertations, and Problem Reports (ETD)

Neurological disorders such as multiple sclerosis (MS) are a major public health concern in the US, with no available therapeutic cure. Chronic neuroinflammation and aberrant proteostasis in the central nervous system (CNS) are the major hallmarks of neurological diseases. Endoplasmic Reticulum (ER) is a major cellular organelle involved in protein synthesis, folding and maturation of various secretory and transmembrane proteins. Pathophysiological stressors such as trauma and infection result in misfolded protein accumulation in the endoplasmic reticulum (ER) lumen, which results in ER stress. To regain proteostasis (protein homeostasis), cells activate the unfolded protein response (UPR). UPR is an evolutionarily conserved …

Beneficial Impacts Of Nod-Like Receptor X1(Nlrx1) Agonism In Lipopolysaccharide-Induced Inflammation, Mena Mansy

Graduate Theses, Dissertations, and Problem Reports (ETD)

Introduction: The regulation of inflammation at the cellular and molecular level is a crucial aspect of homeostasis that is often overlooked, and most treatment options are limited to antibiotics and symptom management drugs. The development of novel molecular-targeted therapy options downstream of pathogen recognition receptors will fulfill the unmet need for therapy to effectively regulate excessive inflammation. NLRX1 is a unique NOD-like receptor that is anti-inflammatory in nature; it has been shown to negatively regulate the NF-kB pathway and has been involved in the pathology of a plethora of inflammatory disorders. This makes NLRX1 an emerging therapeutic molecular target for …

Il-27 Negatively Impacts Immunity Developed Following Bcg Administration, Shelby D. Bradford

Graduate Theses, Dissertations, and Problem Reports (ETD)

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), a predominantly respiratory pathogen responsible for over ten million infections and one million deaths last year. Despite it being a primary objective of the World Health Organization (WHO) for several decades to irradicate TB, progress toward this objective has fallen short of the 2020 target to end TB by 2035. Meeting this goal will require advancements in diagnostic tools, education, healthcare access, and treatments and preventatives. Regarding prevention, the primary tool for this strategy is through vaccination. Currently, the only licensed vaccine for protection against TB is the century old …

Emerging Challenges To Cellular Therapy Of Cancer, Premal D Lulla, Malcolm Brenner

Faculty, Staff and Students Publications

Cellular immunotherapy of cancer in the form of chimeric antigen receptor-modified T-cell therapy has become a standard treatment for lymphoid and more recently plasma cell malignancies. Although their successes in these cancers represent a breakthrough for adoptive cell therapy, there are several challenges to their continued growth in the field of cancer medicine. In this review, we discuss the progress made thus far toward achieving "off-the-shelf" accessibility of cell therapies that has the potential to greatly offset the costs associated with the current practice of making patient-specific products. We also review the innovations under investigation that attempt to make cellular …

Deciphering The Role Of Qpctl In Glioma Progression And Cancer Immunotherapy, Yu'e Liu, Shaojuan Lu, Yihong Sun, Fei Wang, Shibo Yu, Xi Chen, Lei-Lei Wu, Hui Yang, Yufeng Shi, Kaijun Zhao

Faculty, Staff and Students Publications

BACKGROUND: Glioma is the most lethal and most aggressive brain cancer, and currently there is no effective treatment. Cancer immunotherapy is an advanced therapy by manipulating immune cells to attack cancer cells and it has been studied a lot in glioma treatment. Targeting the immune checkpoint CD47 or blocking the CD47-SIRPα axis can effectively eliminate glioma cancer cells but also brings side effects such as anemia. Glutaminyl-peptide cyclotransferase-like protein (QPCTL) catalyzes the pyroglutamylation of CD47 and is crucial for the binding between CD47 and SIRPα. Further study found that loss of intracellular QPCTL limits chemokine function and reshapes myeloid infiltration …

Selective Reprogramming Of Regulatory T Cells In Solid Tumors Can Strongly Enhance Or Inhibit Tumor Growth, Rami Alfar, John V Napoleon, Imrul Shahriar, Richard Finnell, Cole Walchle, Austin Johnson, Philip S Low

Faculty, Staff and Students Publications

Folate receptor delta (FRδ) has been used as a biomarker for regulatory T cells (Tregs), because its expression is limited to Tregs and ovum. Although FRδ is unable to bind folate, we have used molecular docking software to identify a folate congener that binds FRδ with high affinity and have exploited this FRδ-specific ligand to target attached drugs (imaging agents, immune activators, and immune suppressors) specifically to Tregs in murine tumor xenografts. Analysis of treated tumors demonstrates that targeting of a Toll-like receptor 7 agonist inhibits Treg expression of FOXP3, PD-1, CTLA4, and HELIOS, resulting in 40-80% reduction in tumor …

Integrative Metabolomics And Transcriptomics Analysis Reveals Novel Therapeutic Vulnerabilities In Lung Cancer, Jose Thaiparambil, Jianrong Dong, Sandra L Grimm, Dimuthu Perera, Chandra Shekar R Ambati, Vasanta Putluri, Matthew J Robertson, Tajhal D Patel, Brandon Mistretta, Preethi H Gunaratne, Min P Kim, Jason T Yustein, Nagireddy Putluri, Cristian Coarfa, Randa El-Zein

Faculty, Staff and Students Publications

BACKGROUND: Non-small cell lung cancer (NSCLC) comprises the majority (~85%) of all lung tumors, with lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) being the most frequently diagnosed histological subtypes. Multi-modal omics profiling has been carried out in NSCLC, but no studies have yet reported a unique metabolite-related gene signature and altered metabolic pathways associated with LUAD and LUSC.

METHODS: We integrated transcriptomics and metabolomics to analyze 30 human lung tumors and adjacent noncancerous tissues. Differential co-expression was used to identify modules of metabolites that were altered between normal and tumor.

RESULTS: We identified unique metabolite-related gene signatures specific for …

The Nr2f2-Hand2 Signaling Axis Regulates Progesterone Actions In The Uterus At Early Pregnancy, Yeongseok Oh, Elvis Quiroz, Tianyuan Wang, Yassmin Medina-Laver, Skylar Montague Redecke, Francisco Dominguez, John P Lydon, Francesco J Demayo, San-Pin Wu

Faculty, Staff and Students Publications

Endometrial function is dependent on a tight crosstalk between the epithelial and stromal cells of the endometrium. This communication is critical to ensure a fertile uterus and relies on progesterone and estrogen signaling to prepare a receptive uterus for embryo implantation in early pregnancy. One of the key mediators of this crosstalk is the orphan nuclear receptor NR2F2, which regulates uterine epithelial receptivity and stromal cell differentiation. In order to determine the molecular mechanism regulated by NR2F2, RNAseq analysis was conducted on the uterus of

Analysis Of Variable Major Protein Antigenic Variation In The Relapsing Fever Spirochete, Borrelia Miyamotoi, In Response To Polyclonal Antibody Selection Pressure, Robert D Gilmore, Brittany A Armstrong, Kevin S Brandt, Taylor J Van Gundy, Andrias Hojgaard, Job E Lopez, Alexander R Kneubehl

Faculty, Staff and Students Publications

Borrelia miyamotoi is a tick-transmitted spirochete that is genetically grouped with relapsing fever Borrelia and possesses multiple archived pseudogenes that encode variable major proteins (Vmps). Vmps are divided into two groups based on molecular size; variable large proteins (Vlps) and variable small proteins (Vsps). Relapsing fever Borrelia undergo Vmp gene conversion at a single expression locus to generate new serotypes by antigenic switching which is the basis for immune evasion that causes relapsing fever in patients. This study focused on B. miyamotoi vmp expression when spirochetes were subjected to antibody killing selection pressure. We incubated a low passage parent …

Global Regulatory Reforms To Promote Equitable Vaccine Access In The Next Pandemic, Richard Mahoney, Peter J Hotez, Maria Elena Bottazzi

Faculty, Staff and Students Publications

There is broad consensus that the global response to the Covid-19 pandemic was inadequate, leading to unacceptable levels of avoidable morbidity and mortality. Three strategic missteps led to the lack of equitable vaccine access: The heavy reliance on commercial vaccine manufacturers in high-income countries (HICs) versus low- and middle-income countries (LMICs); the emergence of vaccine nationalism restricting and delaying the supply of vaccines to LMICs; and an inadequate support or recognition for LMIC national regulatory authorities. To avoid these inequities in a future pandemic, we focus on three successful vaccine development and technology transfer case studies-the Hepatitis B vaccine produced …

Vaccine-Linked Chemotherapy Improves Cardiac Structure And Function In A Mouse Model Of Chronic Chagas Disease, Kathryn M Jones, Elise N Mangin, Corey L Reynolds, Liliana E Villanueva, Julio Vladimir Cruz, Leroy Versteeg, Brian Keegan, April Kendricks, Jeroen Pollet, Fabian Gusovsky, Maria Elena Bottazzi, Peter J Hotez

Faculty, Staff and Students Publications

INTRODUCTION: Chagas disease, caused by chronic infection with the protozoan parasite Trypanosoma cruzi, affects 6-7 million people worldwide. The major clinical manifestation of Chagas disease is chronic Chagasic cardiomyopathy (CCC), which encompasses a spectrum of symptoms including arrhythmias, hypertrophy, dilated cardiomyopathy, heart failure, and sudden death. Current treatment is limited to two antiparasitic drugs, benznidazole (BNZ) and nifurtimox, but both have limited efficacy to halt the progression of CCC. We developed a vaccine-linked chemotherapy strategy using our vaccine consisting of recombinant Tc24-C4 protein and a TLR-4 agonist adjuvant in a stable squalene emulsion, in combination with low dose benznidazole treatment. …

Heterologous Mrna-Protein Vaccination With Tc24 Induces A Robust Cellular Immune Response Against Trypanosoma Cruzi, Characterized By An Increased Level Of Polyfunctional Cd8+ T-Cells, Cristina Poveda, Ana Carolina Leão, Chiara Mancino, Francesca Taraballi, Yi-Lin Chen, Rakesh Adhikari, Maria Jose Villar, Rakhi Kundu, Duc M Nguyen, Leroy Versteeg, Ulrich Strych, Peter J Hotez, Maria Elena Bottazzi, Jeroen Pollet, Kathryn M Jones

Faculty, Staff and Students Publications

Tc24 is a Trypanosoma cruzi-derived flagellar protein that, when formulated with a TLR-4 agonist adjuvant, induces a balanced immune response in mice, elevating IgG2a antibody titers and IFN-γ levels. Furthermore, vaccination with the recombinant Tc24 protein can reduce parasite levels and improve survival during acute infection. Although some mRNA vaccines have been proven to elicit a stronger immune response than some protein vaccines, they have not been used against T. cruzi. This work evaluates the immunogenicity of a heterologous prime/boost vaccination regimen using protein and mRNA-based Tc24 vaccines. Mice (C57BL/6) were vaccinated twice subcutaneously, three weeks apart, with …

Prevalence Of Trypanosoma Cruzi, The Etiologic Agent Of Chagas Disease, Infection In Texas Skunks (Mammalia: Mephitidae), Bonnie E Gulas-Wroblewski, Rodion Gorchakov, Rebecca B Kairis, Robert C Dowler, Kristy O Murray

Faculty, Staff and Students Publications

Background:

Chagas disease is one of the world's most neglected tropical diseases, infecting over six million people across the Americas. The hemoparasite Trypanosoma cruzi is the etiological agent for the disease, circulating in domestic, peridomestic, and sylvatic transmission cycles that are maintained by triatomine vectors and a diversity of wild and synanthropic hosts. Public health and wildlife management interventions targeting the interruption of T. cruzi transmission rely on an understanding of the dynamics driving the ecology of this zoonotic pathogen. One wildlife host that purportedly plays a role in the transmission of Chagas disease within the southern United States is …

Immunomodulatory Proteins From Hookworms Reduce Cardiac Inflammation And Modulate Regulatory Responses In A Mouse Model Of Chronic Trypanosoma Cruzi Infection, Kathryn M Jones, Bin Zhan, Keenan J Ernste, Maria Jose Villar, Nalini Bisht, Duc Nguyen, Li-Yen Chang, Cristina Poveda, Gonteria J Robinson, Akshar J Trivedi, Colby J Hofferek, William K Decker, Vanaja Konduri

Faculty, Staff and Students Publications

Introduction

Hookworms are parasitic helminths that secrete a variety of proteins that induce anti-inflammatory immune responses, stimulating increased CD4+Foxp3+ regulatory T cells and IL-10 production. Hookworm-derived recombinant proteins AIP-1 and AIP-2 have been shown to reduce inflammation in mouse models of inflammatory bowel disease and inflammatory airway disease by inducing CD4+Foxp3+ cells and IL-10 production. In contrast, chronic infection with the protozoal parasite Trypanosoma cruzi, the causative agent of Chagas disease, leads to chronic inflammation in tissues. Persistence of the parasites in tissues drives chronic low-grade inflammation, with increased infiltration of inflammatory cells into the heart, accompanied by increased …

Cloud-Native Distributed Genomic Pileup Operations, Marek Wiewiórka, Agnieszka Szmurło, Paweł Stankiewicz, Tomasz Gambin

Faculty, Staff and Students Publications

MOTIVATION: Pileup analysis is a building block of many bioinformatics pipelines, including variant calling and genotyping. This step tends to become a bottleneck of the entire assay since the straightforward pileup implementations involve processing of all base calls from all alignments sequentially. On the other hand, a distributed version of the algorithm faces the intrinsic challenge of splitting reads-oriented file formats into self-contained partitions to avoid costly data exchange between computational nodes.

RESULTS: Here, we present a scalable, distributed and efficient implementation of a pileup algorithm that is suitable for deploying in cloud computing environments. In particular, we implemented: (i) …

The Neurobiology Of Duration Of Untreated Psychosis: A Comprehensive Review, Anthony W Zoghbi, Jeffrey A Lieberman, Ragy R Girgis

Faculty, Staff and Students Publications

Duration of untreated psychosis (DUP) is defined as the time from the onset of psychotic symptoms until the first treatment. Studies have shown that longer DUP is associated with poorer response rates to antipsychotic medications and impaired cognition, yet the neurobiologic correlates of DUP are poorly understood. Moreover, it has been hypothesized that untreated psychosis may be neurotoxic. Here, we conducted a comprehensive review of studies that have examined the neurobiology of DUP. Specifically, we included studies that evaluated DUP using a range of neurobiologic and imaging techniques and identified 83 articles that met inclusion and exclusion criteria. Overall, 27 …