Digital Commons Network^™

Meta-Analysis Comparing Outcomes Of High-Power Short-Duration And Low-Power Long-Duration Radiofrequency Ablation For Atrial Fibrillation, Dibbendhu Khanra, Abdul Hamid, Saurabh Deshpande, Anindya Mukherjee, Sanjiv Petkar, Mohammad Saeed, Indranill Basu-Ray

Faculty, Staff and Students Publications

OBJECTIVE: High power short duration (HPSD) ablation strategy is proposed to be more effective than low power long duration (LPLD) for radiofrequency ablation of atrial fibrillation. Although small trials abound, data from a large cohort are lacking. This meta-analysis compares all the existing studies comparing these two approaches to evaluate perceived advantages of one over the other.

METHODS: A systematic search of PubMed, EMBASE, and Cochrane databases identified studies comparing HPSD to LPLD ablation. All the analyses used the random-effects model.

RESULTS: Ablation settings varied widely across 20 studies comprising 2,136 patients who underwent HPSD and 1,753 patients who underwent …

Unique Challenges To Diagnosing Human Herpesvirus-6 (Hhv-6) Encephalitis Following Post-Hematopoietic Stem Cell Transplant: A Case And Brief Review, Harrison Zhu, Amir Ali, Karrune V Woan, Eric Tam, George Yaghmour, Alan Flores, Preet Chaudhary

Faculty, Staff and Students Publications

A patient with an ultimate diagnosis of human herpesvirus-6 (HHV-6) encephalitis developed central nervous system (CNS) symptoms 13 days after undergoing myeloablative haploidentical allogeneic hematopoietic stem cell transplant (HSCT). Due to the patient's body habitus, magnetic resonance (MR) imaging was not obtained until the onset of retrograde amnesia on day +24. MR imaging and other clinical findings eliminated all skepticism of HHV-6 encephalitis and HHV-6 antivirals were initiated on day +28, leading to gradual recovery. This case demonstrates some of the factors that may complicate the diagnosis of post-alloHSCT HHV-6 encephalitis. Because HHV-6 encephalitis and viremia can occur without warning, …

Modified Vaccinia Ankara Expressing Eehv1a Glycoprotein B Elicits Humoral And Cell-Mediated Immune Responses In Mice, Taylor Pursell, Jennifer L Spencer Clinton, Jie Tan, Rongsheng Peng, Paul D Ling

Faculty, Staff and Students Publications

Elephant endotheliotropic herpesvirus (EEHV) can cause lethal hemorrhagic disease (EEHV-HD) in Asian elephants and is the largest cause of death in captive juvenile Asian elephants in North America and Europe. EEHV-HD also has been documented in captive and wild elephants in their natural range countries. A safe and effective vaccine to prevent lethal EEHV infection would significantly improve conservation efforts for this endangered species. Recent studies from our laboratory suggest that EEHV morbidity and mortality are often associated with primary infection. Therefore, we aim to generate a vaccine, particularly for EEHV1 naïve animals, with the goal of preventing lethal EEHV-HD. …

Gut Microbiota From Sjögren Syndrome Patients Causes Decreased T Regulatory Cells In The Lymphoid Organs And Desiccation-Induced Corneal Barrier Disruption In Mice, Laura Schaefer, Claudia M Trujillo-Vargas, Firas S Midani, Stephen C Pflugfelder, Robert A Britton, Cintia S De Paiva

Faculty, Staff and Students Publications

Sjögren syndrome (SS) is an autoimmune inflammatory disorder characterized by secretory dysfunction in the eye and mouth; in the eye, this results in tear film instability, reduced tear production, and corneal barrier disruption. A growing number of studies show that homeostasis of the ocular surface is impacted by the intestinal microbiome, and several 16S sequencing studies have demonstrated dysbiosis of the intestinal microbiota in SS patients. In this study, we utilized metagenomic sequencing to perform a deeper analysis of the intestinal microbiome using stools collected from sex- and age-matched healthy (n = 20), dry eye (n = 4) …

Steroid Receptor Coactivators – Their Role In Immunity, Yosi Gilad, David M Lonard, Bert W O'Malley

Faculty, Staff and Students Publications

Steroid Receptor Coactivators (SRCs) are essential regulators of transcription with a wide range of impact on human physiology and pathology. In immunology, SRCs play multiple roles; they are involved in the regulation of nuclear factor-κB (NF-κB), macrophage (MΦ) activity, lymphoid cells proliferation, development and function, to name just a few. The three SRC family members, SRC-1, SRC-2 and SRC-3, can exert their immunological function either in an independent manner or act in synergy with each other. In certain biological contexts, one SRC family member can compensate for lack of activity of another member, while in other cases one SRC can …

A Steroid Receptor Coactivator Small Molecule "Stimulator" Attenuates Post-Stroke Ischemic Brain Injury, Lisa K Mcclendon, Roberto L Garcia, Tyler Lazaro, Ariadna Robledo, Viren Vasandani, Zean Aaron Evan Luna, Abhijit S Rao, Aditya Srivatsan, David M Lonard, Clifford C Dacso, Peter Kan, Bert W O'Malley

Faculty, Staff and Students Publications

Introduction: Pathologic remodeling of the brain following ischemic stroke results in neuronal loss, increased inflammation, oxidative stress, astrogliosis, and a progressive decrease in brain function. We recently demonstrated that stimulation of steroid receptor coactivator 3 with the small-molecule stimulator MCB-613 improves cardiac function in a mouse model of myocardial ischemia. Since steroid receptor coactivators are ubiquitously expressed in the brain, we reasoned that an MCB-613 derivative (MCB-10-1), could protect the brain following ischemic injury. To test this, we administered MCB-10-1 to rats following middle cerebral artery occlusion and reperfusion.

Methods: Neurologic impairment and tissue damage responses were evaluated on day …

Selective Vulnerability Of The Intermediate Retinal Capillary Plexus Precedes Retinal Ganglion Cell Loss In Ocular Hypertension, Priyamvada M Pitale, Guofu Shen, Rohini R Sigireddi, Maria Polo-Prieto, Yong H Park, Solomon E Gibson, Peter D Westenskow, Roomasa Channa, Benjamin J Frankfort

Faculty, Staff and Students Publications

Introduction: Glaucoma, a disease of retinal ganglion cell (RGC) injury and potentially devastating vision loss, is associated with both ocular hypertension (OHT) and reduced ocular blood flow. However, the relationship between OHT and retinal capillary architecture is not well understood. In this project, we studied microvasculature damage in mice exposed to mild levels of induced OHT.

Methods: Mild OHT was induced with the microbead model for 2 weeks. At this time point, some retinas were immunostained with CD31 (endothelium), Collagen IV (basement membrane), and RBPMS (RGCs) for z-stack confocal microscopy. We processed these confocal images to distinguish the three retinal …

Selectively Targeting Disease-Restricted Secretogranin Iii To Alleviate Choroidal Neovascularization, Liyang Ji, Prabuddha Waduge, Lili Hao, Avinash Kaur, Wencui Wan, Yan Wu, Hong Tian, Jinsong Zhang, Keith A Webster, Wei Li

Faculty, Staff and Students Publications

Choroidal neovascularization (CNV), a leading cause of blindness in the elderly, is routinely treated with vascular endothelial growth factor (VEGF) inhibitors that have limited efficacy and potentially adverse side effects. An unmet clinical need is to develop novel therapies against other angiogenic factors for alternative or combination treatment to improve efficacy and safety. We recently described secretogranin III (Scg3) as a disease-selective angiogenic factor, causally linked to diabetic retinopathy and acting independently of the VEGF pathway. An important question is whether such a disease-selective Scg3 pathway contributes to other states of pathological angiogenesis beyond diabetic retinopathy. By applying a novel …

Spatial Transcriptomics Of The Lacrimal Gland Features Macrophage Activity And Epithelium Metabolism As Key Alterations During Chronic Inflammation, Olivier Mauduit, Vanessa Delcroix, Takeshi Umazume, Cintia S De Paiva, Darlene A Dartt, Helen P Makarenkova

Faculty, Staff and Students Publications

The lacrimal gland (LG) is an exocrine gland that produces the watery part of the tear film that lubricates the ocular surface. Chronic inflammation, such as Sjögren’s syndrome (SS), is one of the leading causes of aqueous-deficiency dry eye (ADDE) disease worldwide. In this study we analyzed the chronic inflammation in the LGs of the NOD.B10Sn-H2b/J (NOD.H-2b) mice, a mouse model of SS, utilizing bulk RNAseq and Visium spatial gene expression. With Seurat we performed unsupervised clustering and analyzed the spatial cell distribution and gene expression changes in all cell clusters within the LG sections. Moreover, for the …

In Silico Integrative Analysis Of Multi-Omics Reveals Regulatory Layers For Diurnal Gene Expression In Mouse Liver, Chunjie Jiang, Panpan Liu, Cam Mong La, Dongyin Guan

Faculty, Staff and Students Publications

Diurnal oscillation persists throughout the body and plays an essential role in maintaining physiological homeostasis. Disruption of diurnal rhythm contributes to many diseases including type 2 diabetes. The regulatory mechanism of the transcription-translation feedback loop (TTFL) of core clock genes is well-established, while a systematic study across all regulatory layers of gene expression, including gene transcription, RNA translation, and DNA binding protein (DBP) activities, is still lacking. We comprehensively bioinformatics analyzed the rhythmicity of gene transcription, mature RNA abundance, protein abundance and DBP activity using publicly available omic-datasets from mouse livers. We found that the core clock genes,

A Novel Model Of Gestational Diabetes: Acute High Fat High Sugar Diet Results In Insulin Resistance And Beta Cell Dysfunction During Pregnancy In Mice, Akansha Mishra, Simone Hernandez Ruano, Pradip K Saha, Kathleen A Pennington

Faculty, Staff and Students Publications

Gestational diabetes mellitus (GDM) affects 7–18% of all pregnancies. Despite its high prevalence, there is no widely accepted animal model. To address this, we recently developed a mouse model of GDM. The goal of this work was to further characterize this animal model by assessing insulin resistance and beta cell function. Mice were randomly assigned to either control (CD) or high fat, high sugar (HFHS) diet and mated 1 week later. At day 0 (day of mating) mice were fasted and intraperitoneal insulin tolerance tests (ipITT) were performed. Mice were then euthanized and pancreata were collected for histological analysis. Euglycemic …

The Third International Hackathon For Applying Insights Into Large-Scale Genomic Composition To Use Cases In A Wide Range Of Organisms, Kimberly Walker, Divya Kalra, Rebecca Lowdon, Guangyi Chen, David Molik, Daniela C Soto, Fawaz Dabbaghie, Ahmad Al Khleifat, Medhat Mahmoud, Luis F Paulin, Muhammad Sohail Raza, Susanne P Pfeifer, Daniel Paiva Agustinho, Elbay Aliyev, Pavel Avdeyev, Enrico R Barrozo, Sairam Behera, Kimberley Billingsley, Li Chuin Chong, Deepak Choubey, Wouter De Coster, Yilei Fu, Alejandro R Gener, Timothy Hefferon, David Morgan Henke, Wolfram Höps, Anastasia Illarionova, Michael D Jochum, Maria Jose, Rupesh K Kesharwani, Sree Rohit Raj Kolora, Jędrzej Kubica, Priya Lakra, Damaris Lattimer, Chia-Sin Liew, Bai-Wei Lo, Chunhsuan Lo, Anneri Lötter, Sina Majidian, Suresh Kumar Mendem, Rajarshi Mondal, Hiroko Ohmiya, Nasrin Parvin, Carolina Peralta, Chi-Lam Poon, Ramanandan Prabhakaran, Marie Saitou, Aditi Sammi, Philippe Sanio, Nicolae Sapoval, Najeeb Syed, Todd Treangen, Gaojianyong Wang, Tiancheng Xu, Jianzhi Yang, Shangzhe Zhang, Weiyu Zhou, Fritz J Sedlazeck, Ben Busby

Faculty, Staff and Students Publications

In October 2021, 59 scientists from 14 countries and 13 U.S. states collaborated virtually in the Third Annual Baylor College of Medicine & DNANexus Structural Variation hackathon. The goal of the hackathon was to advance research on structural variants (SVs) by prototyping and iterating on open-source software. This led to nine hackathon projects focused on diverse genomics research interests, including various SV discovery and genotyping methods, SV sequence reconstruction, and clinically relevant structural variation, including SARS-CoV-2 variants. Repositories for the projects that participated in the hackathon are available at https://github.com/collaborativebioinformatics.

Problems In Csf And Ophthalmic Disease Research, Ryan Machiele, Benjamin Jay Frankfort, Hanspeter Esriel Killer, David Fleischman

Faculty, Staff and Students Publications

There has been significant interest and progress in the understanding of cerebrospinal fluid pressure and its relationship to glaucoma and other ophthalmic diseases. However, just as every physiologic fluid pressure fluctuates, cerebrospinal fluid pressure (CSFP) is similarly dynamic. Coupling this with the difficulty in measuring the pressure, there are many obstacles in furthering this field of study. This review highlights some of the difficulties in CSFP research, including fluid compartmentalization, estimation equations, and pressure fluctuation. Keeping these limitations in mind will hopefully improve the quality and context of this burgeoning field.

Systematic Profiling Of Dnmt3a Variants Reveals Protein Instability Mediated By The Dcaf8 E3 Ubiquitin Ligase Adaptor, Yung-Hsin Huang, Chun-Wei Chen, Venkatasubramaniam Sundaramurthy, Mikołaj Słabicki, Dapeng Hao, Caroline J Watson, Ayala Tovy, Jaime M Reyes, Olga Dakhova, Brielle R Crovetti, Christina Galonska, Minjung Lee, Lorenzo Brunetti, Yubin Zhou, Katrina Tatton-Brown, Yun Huang, Xiaodong Cheng, Alexander Meissner, Peter J M Valk, Lionel Van Maldergem, Mathijs A Sanders, Jamie R Blundell, Wei Li, Benjamin L Ebert, Margaret A Goodell

Faculty, Staff and Students Publications

Clonal hematopoiesis is a prevalent age-related condition associated with a greatly increased risk of hematologic disease; mutations in DNA methyltransferase 3A (DNMT3A) are the most common driver of this state. DNMT3A variants occur across the gene with some particularly associated with malignancy, but the functional relevance and mechanisms of pathogenesis of the majority of mutations are unknown. Here, we systematically investigated the methyltransferase activity and protein stability of 253 disease-associated DNMT3A mutations, and found that 74% were loss-of-function mutations. Half of these variants exhibited reduced protein stability and, as a class, correlated with greater clonal expansion and acute …

The Autophagic Protein P62 Is A Target Of Reactive Aldehydes In Human And Murine Cholestatic Liver Disease, Colin T Shearn, Aimee L Anderson, Michael W Devereux, David J Orlicky, Cole Michel, Dennis R Petersen, Colin G Miller, Sanjiv Harpavat, Edward E Schmidt, Ronald J Sokol

Faculty, Staff and Students Publications

Inflammatory cholestatic liver diseases, including Primary Sclerosing Cholangitis (PSC), are characterized by periportal inflammation with progression to cirrhosis. The objective of this study was to examine interactions between oxidative stress and autophagy in cholestasis. Using hepatic tissue from male acute cholestatic (bile duct ligated) as well as chronic cholestatic (Mdr2KO) mice, localization of oxidative stress, the antioxidant response and induction of autophagy were analyzed and compared to human PSC liver. Concurrently, the ability of reactive aldehydes to post-translationally modify the autophagosome marker p62 was assessed in PSC liver tissue and in cell culture. Expression of autophagy markers was upregulated in …

Clinical Outcome And Gut Development After Insulin-Like Growth Factor-1 Supplementation To Preterm Pigs, Kristine Holgersen, Martin Bo Rasmussen, Galen Carey, Douglas G Burrin, Thomas Thymann, Per Torp Sangild

Faculty, Staff and Students Publications

BACKGROUND: Elevation of circulating insulin-like growth factor-1 (IGF-1) within normal physiological levels may alleviate several morbidities in preterm infants but safety and efficacy remain unclear. We hypothesized that IGF-1 supplementation during the first 1-2 weeks after preterm birth improves clinical outcomes and gut development, using preterm pigs as a model for infants.

METHODS: Preterm pigs were given vehicle or recombinant human IGF-1/binding protein-3 (rhIGF-1, 2.25 mg/kg/d) by subcutaneous injections for 8 days (Experiment 1, n = 34), or by systemic infusion for 4 days (Experiment 2, n = 19), before collection of blood and organs for analyses.

RESULTS: In both …

Exercise-Induced Myokines Downregulates The Ace2 Level In Bronchial Epithelial Cells: Implications For Sars-Cov-2 Prevention, Vaishali Bhardwaj, Mart Dela Cruz, Deepika Subramanyam, Rohit Kumar, Sandeep Markan, Beth Parker, Hemant K Roy

Faculty, Staff and Students Publications

BACKGROUND: The Covid-19 pandemic has emerged as the leading public health challenge of our time (20th century). While vaccinations have finally blunted the death rate, concern has remained about more virulent forms highlighting the need for alternative approaches. Epidemiological studies indicate that physical activity has been shown to decrease the risk of infection of some respiratory viruses. Part of the salutary effects of exercise is believed to be through the elaboration of cytokines by contracting skeletal muscles (termed myokines). The objective of this study was to investigate whether exercise-induced myokines would mitigate the SARS-CoV-2 infectivity of the bronchial epithelium through …

Rev-Erb Is Essential In Cardiac Fibroblasts Homeostasis, Xiaokang Luo, Shiyang Song, Lei Qi, Chih-Liang Tien, Hui Li, Weiyi Xu, Theodore Lemuel Mathuram, Thomas Burris, Yuanbiao Zhao, Zheng Sun, Lilei Zhang

Faculty, Staff and Students Publications

REV-ERB agonists have shown antifibrotic effects in the heart and other organs. The function of REV-ERB in the cardiac fibroblasts remains unstudied. Here, we characterize the functional difference of REV-ERB in mouse embryonic fibroblasts and cardiac fibroblasts using genetic deletion of REV-ERBα and ß in vitro. We show that REV-ERB α/β double deleted cardiac fibroblasts have reduced viability and proliferation, but increased migration and myofibroblasts activation. Thus, REV-ERB α/β has essential cell-autonomous role in cardiac fibroblasts in maintaining them in a healthy, quiescent state. We also show that existing REV-ERB agonist SR9009 strongly suppresses cardiac fibroblasts activation but in …

Hypermethylation Of Pi3k-Akt Signalling Pathway Genes Is Associated With Human Neural Tube Defects, Tian Tian, Xinyuan Lai, Kuanhui Xiang, Xiao Han, Shengju Yin, Robert M Cabrera, John W Steele, Yunping Lei, Xuanye Cao, Richard H Finnell, Linlin Wang, Aiguo Ren

Faculty, Staff and Students Publications

Neural tube defects (NTDs) are a group of common and severe congenital malformations. The PI3K-AKT signalling pathway plays a crucial role in the neural tube development. There is limited evidence concerning any possible association between aberrant methylation in PI3K-AKT signalling pathway genes and NTDs. Therefore, we aimed to investigate potential associations between aberrant methylation of PI3K-AKT pathway genes and NTDs. Methylation studies of PI3K-AKT pathway genes utilizing microarray genome-methylation data derived from neural tissues of ten NTD cases and eight non-malformed controls were performed. Targeted DNA methylation analysis was subsequently performed in an independent cohort of 73 NTD cases and …

Initial Experiences Using Plasma Rich In Growth Factors To Treat Keratoneuralgia, Margaret Wang, Sowmya Yennam, Stephen Pflugfelder

Faculty, Staff and Students Publications

Keratoneuralgia, a clinical diagnosis of sensitized corneal pain without visible ocular surface damage, generally has minimal response to conventional therapies. Causes include refractive surgery and chronic dry eye. We evaluated the efficacy of Plasma Rich in Growth Factors (PRGF), a novel treatment prepared using a commercially available kit, in patients with keratoneuralgia. A retrospective chart review identified patients who had the clinical diagnosis of keratoneuralgia and were treated with PRGF for at least 3 months from October 2015 to April 2020 at a single academic institution. Both objective eye exam findings and concurrent treatments were obtained at baseline, 3 months, …

Il-17 Producing Lymphocytes Cause Dry Eye And Corneal Disease With Aging In Rxrα Mutant Mouse, Jehan Alam, Ghasem Yazdanpanah, Rinki Ratnapriya, Nicholas Borcherding, Cintia S De Paiva, Dequan Li, Rodrigo Guimaraes De Souza, Zhiyuan Yu, Stephen C Pflugfelder

Faculty, Staff and Students Publications

PURPOSE: To investigate IL-17 related mechanisms for developing dry eye disease in the Pinkie mouse strain with a loss of function RXRα mutation.

METHODS: Measures of dry eye disease were assessed in the cornea and conjunctiva. Expression profiling was performed by single-cell RNA sequencing (scRNA-seq) to compare gene expression in conjunctival immune cells. Conjunctival immune cells were immunophenotyped by flow cytometry and confocal microscopy. The activity of RXRα ligand 9-cis retinoic acid (RA) was evaluated in cultured monocytes and γδ T cells.

RESULTS: Compared to wild type (WT) C57BL/6, Pinkie has increased signs of dry eye disease, including decreased tear …

New, Potent, Small Molecule Agonists Of Tyrosine Kinase Receptors Attenuate Dry Eye Disease, Zhiyuan Yu, Shaon Joy, Tianxiong Mi, Ghasem Yazdanpanah, Kevin Burgess, Cintia S De Paiva

Faculty, Staff and Students Publications

Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin3 (NT-3) bind to tyrosine kinase (Trk) receptors, TrkA, TrkB, and TrkC, respectively. This study investigated the efficacy of novel molecule agonists of Trk receptors in an in vivo model of dry eye disease (DED). Small molecule TrkC agonist (C1) and a pan-Trk agonist (pan) were synthesized for this. C57BL/6J mice were subjected to desiccating stress (DS) and received bilateral eye drops of C1, pan, or vehicle (2x/day). Dry eye signs, inflammation and expression of corneal barrier function, and conjunctival goblet cell (GC) densities were measured as part of the DED …

Proceedings Of The 10th Annual Deep Brain Stimulation Think Tank: Advances In Cutting Edge Technologies, Artificial Intelligence, Neuromodulation, Neuroethics, Interventional Psychiatry, And Women In Neuromodulation, Joshua K Wong, Helen S Mayberg, Doris D Wang, R Mark Richardson, Casey H Halpern, Lothar Krinke, Mattia Arlotti, Lorenzo Rossi, Alberto Priori, Sara Marceglia, Ro'ee Gilron, James F Cavanagh, Jack W Judy, Svjetlana Miocinovic, Annaelle D Devergnas, Roy V Sillitoe, Stephanie Cernera, Carina R Oehrn, Aysegul Gunduz, Wayne K Goodman, Erika A Petersen, Helen Bronte-Stewart, Robert S Raike, Mahsa Malekmohammadi, David Greene, Petra Heiden, Huiling Tan, Jens Volkmann, Valerie Voon, Luming Li, Pankaj Sah, Terry Coyne, Peter A Silburn, Cynthia S Kubu, Anna Wexler, Jennifer Chandler, Nicole R Provenza, Sarah R Heilbronner, Marta San Luciano, Christopher J Rozell, Michael D Fox, Coralie De Hemptinne, Jaimie M Henderson, Sameer A Sheth, Michael S Okun

Faculty, Staff and Students Publications

The deep brain stimulation (DBS) Think Tank X was held on August 17–19, 2022 in Orlando FL. The session organizers and moderators were all women with the theme women in neuromodulation. Dr. Helen Mayberg from Mt. Sinai, NY was the keynote speaker. She discussed milestones and her experiences in developing depression DBS. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers and researchers (from industry and academia) can freely discuss current and emerging DBS technologies as well as the logistical and ethical issues facing the field. The consensus among the DBS Think …

Targeting The Pro-Survival Protein Bcl-2 To Prevent Breast Cancer, Adelaide Young, Wen Bu, Weiyu Jiang, Amy Ku, Jyoti Kapali, Sagar Dhamne, Lan Qin, Susan G Hilsenbeck, Yi-Chieh Nancy Du, Yi Li

Faculty, Staff and Students Publications

Current chemopreventive strategies require 3-5 years of continuous treatment and have the concerns of significant side effects; therefore, new chemopreventive agents that require shorter and safer treatments are urgently needed. In this study, we developed a new murine model of breast cancer that mimics human breast cancer initiation and is ideal for testing the efficacy of chemopreventive therapeutics. In this model, introduction of lentivirus carrying a PIK3CA gene mutant commonly found in breast cancers infects a small number of the mammary cells, leading to atypia first and then to ductal carcinomas that are positive for both estrogen receptor and progesterone …

Loss Of H2r Signaling Disrupts Neutrophil Homeostasis And Promotes Inflammation-Associated Colonic Tumorigenesis In Mice, Zhongcheng Shi, Yuko Mori-Akiyama, Wa Du, Robert Fultz, Yanling Zhao, Wenly Ruan, Susan Venable, Melinda A Engevik, James Versalovic

Faculty, Staff and Students Publications

BACKGROUND & AIMS: We previously showed that histamine suppressed inflammation-associated colonic tumorigenesis through histamine type 2 receptor (H2R) signaling in mice. This study aimed to precisely elucidate the downstream effects of H2R activation in innate immune cells.

METHODS: Analyses using online databases of single-cell RNA sequencing of intestinal epithelial cells in mice and RNA sequencing of mouse immune cells were performed to determine the relative abundances of 4 histamine receptors among different cell types. Mouse neutrophils, which expressed greater amounts of H2R, were collected from the peritoneum of wild-type and H2R-deficient mice, of which low-density and high-density neutrophils were extracted …

Development Of Phage Cocktails To Treate Coli Catheter-Associated Urinary Tract Infection And Associated Biofilms, Belkys C Sanchez, Emmaline R Heckmann, Sabrina I Green, Justin R Clark, Heidi B Kaplan, Robert F Ramig, Casey Hines-Munson, Felicia Skelton, Barbara W Trautner, Anthony W Maresso

Faculty, Staff and Students Publications

High rates of antimicrobial resistance and formation of biofilms makes treatment of Escherichia coli catheter-associated urinary tract infections (CAUTI) particularly challenging. CAUTI affect 1 million patients per year in the United States and are associated with morbidity and mortality, particularly as an etiology for sepsis. Phage have been proposed as a potential therapeutic option. Here, we report the development of phage cocktails that lyse contemporary E. coli strains isolated from the urine of patients with spinal cord injury (SCI) and display strong biofilm-forming properties. We characterized E. coli phage against biofilms in two in vitro CAUTI models. Biofilm viability was …

Development Of Phage Cocktails To Treat E Coli Catheter-Associated Urinary Tract Infection And Associated Biofilms, Belkys C Sanchez, Emmaline R Heckmann, Sabrina I Green, Justin R Clark, Heidi B Kaplan, Robert F Ramig, Casey Hines-Munson, Felicia Skelton, Barbara W Trautner, Anthony W Maresso

Faculty, Staff and Students Publications

High rates of antimicrobial resistance and formation of biofilms makes treatment of Escherichia coli catheter-associated urinary tract infections (CAUTI) particularly challenging. CAUTI affect 1 million patients per year in the United States and are associated with morbidity and mortality, particularly as an etiology for sepsis. Phage have been proposed as a potential therapeutic option. Here, we report the development of phage cocktails that lyse contemporary E. coli strains isolated from the urine of patients with spinal cord injury (SCI) and display strong biofilm-forming properties. We characterized E. coli phage against biofilms in two in vitro CAUTI models. Biofilm viability was …

Interleukin-1Β Secretion Induced By Mucosa-Associated Gut Commensal Bacteria Promotes Intestinal Barrier Repair, Wan-Jung H Wu, Myunghoo Kim, Lin-Chun Chang, Adrien Assie, Fatima B Saldana-Morales, Daniel F Zegarra-Ruiz, Kendra Norwood, Buck S Samuel, Gretchen E Diehl

Faculty, Staff and Students Publications

The gut microbiota is essential for maintenance and repair of the intestinal epithelial barrier. As shifts in both intestinal epithelial barrier function and microbiota composition are found in inflammatory bowel disease patients, it is critical to understand the role of distinct bacteria in regulating barrier repair. We identified a mouse commensal E. coli isolate, GDAR2-2, that protects mice from Citrobacter rodentium infection and dextran sulfate sodium-induced colitis. Colonization with GDAR2-2 in mice resulted in expansion of CX3CR1+ mononuclear phagocytes, including CX3CR1+ macrophages/dendritic cells and monocytes, along with IL-22-secreting type 3 innate lymphoid cells and improved epithelial barrier function. In vitro …

Adrenomedullin And Its Receptors Are Expressed In Mouse Pancreatic Β-Cells And Suppresses Insulin Synthesis And Secretion, Yuanlin Dong, Simone Hernandez Ruano, Akansha Mishra, Kathleen A Pennington, Chandrasekhar Yallampalli

Faculty, Staff and Students Publications

Gestational diabetes mellitus (GDM) is associated with defective pancreatic β-cell adaptation in pregnancy, but the underlying mechanism remains obscure. Our previous studies demonstrated that GDM women display increased plasma adrenomedullin (ADM) levels, and non-obese GDM mice show decreased serum concentrations of insulin and the number of β-cells in pancreas islets. The aims of this study is to examine if ADM and its receptors are expressed in female mouse pancreas, and if so, whether insulin secretion is regulated by ADM in mouse β-cell line, NIT-1 cells and isolated mouse pancreatic islets. Present study shows that ADM and its receptor components CRLR, …

Foxo1 Is Present In Stomach Epithelium And Determines Gastric Cell Distribution, Wendy M Mckimpson, Taiyi Kuo, Takumi Kitamoto, Sei Higuchi, Jason C Mills, Rebecca A Haeusler, Domenico Accili

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Stomach cells can be converted to insulin-producing cells by Neurog3, MafA, and Pdxl over-expression. Enteroendocrine cells can be similarly made to produce insulin by the deletion of FOXO1. Characteristics and functional properties of FOXO1-expressing stomach cells are not known.

METHODS: Using mice bearing a FOXO1-GFP knock-in allele and primary cell cultures, we examined the identity of FOXO1-expressing stomach cells and analyzed their features through loss-of-function studies with red-to-green fluorescent reporters.

RESULTS: FOXO1 localizes to a subset of Neurog3 and parietal cells. FOXO1 deletion ex vivo or in vivo using Neurog3-cre or Atp4b-cre increased numbers of parietal cells, …