Digital Commons Network^™

Probiotics And Human Milk Differentially Influence The Gut Microbiome And Nec Incidence In Preterm Pigs, Jinxin Liu, Lee Call, Gregory Guthrie, Nick Jensen, Amy B Hair, David A Mills, Douglas G Burrin

Faculty, Staff and Students Publications

Necrotizing enterocolitis (NEC) is the leading cause of death caused by gastrointestinal disease in preterm infants. Major risk factors include prematurity, formula feeding, and gut microbial colonization. Microbes have been linked to NEC, yet there is no evidence of causal species, and select probiotics have been shown to reduce NEC incidence in infants. In this study, we evaluated the effect of the probiotic Bifidobacterium longum subsp. infantis (BL. infantis), alone and in combination with a human milk oligosaccharide (HMO)—sialylactose (3′SL)—on the microbiome, and the incidence of NEC in preterm piglets fed an infant formula diet. We studied 50 …

Steroidal Or Non-Steroidal Mras: Should We Still Enable Raasi Use Through K Binders?

Faculty, Staff and Students Publications

Renin-angiotensin-aldosterone system inhibitors (RAASi) and mineralocorticoid receptor antagonists (MRAs) are important interventions to improve outcomes in patients with chronic kidney disease and heart failure, but their use is limited in some patients by the development of hyperkalemia. The risk of hyperkalemia may differ between agents, with one trial showing lower risk of hyperkalemia with the novel non-steroidal MRA finerenone compared with steroidal MRA spironolactone. Novel potassium binders, including patiromer and sodium zirconium cyclosilicate, are available interventions to manage hyperkalemia and enable continuation of RAASi and MRAs in patients who could benefit from these treatments. These agents bind free potassium ions …

The Efficiency Of P27 Cleavage During In Vitro Respiratory Syncytial Virus (Rsv) Infection Is Cell Line And Rsv Subtype Dependent, Alexandre F Carisey, Vasanthi Avadhanula, Pedro A Piedra

Faculty, Staff and Students Publications

Respiratory syncytial virus (RSV) fusion protein (F) is highly conserved between subtypes A and B (RSV/A and RSV/B). To become fully active, F precursor undergoes enzymatic cleavage to yield F1 and F2 subunits and releases a 27-amino-acid peptide (p27). Virus-cell fusion occurs when RSV F undergoes a conformational change from pre-F to post-F. Previous data show that p27 is detected on RSV F, but questions remain regarding if and how p27 affects the conformation of mature RSV F. Monoclonal antibodies against p27, site Ø (pre-F specific), and site II were used to monitor RSV F conformation by enzyme-linked immunosorbent assay …

Functional Impact Of Ethyl-Β-D-Glucuronide On Mycobacterium Tuberculosis Stimulated Lung Macrophages, Charles Inaku

Biotechnology Theses

Chronic alcohol abuse has been shown to alter immune defense mechanisms in humans and mice which makes the host susceptible to infections, including Mycobacterium tuberculosis (Mtb) infection. However, limited information is available on the mechanisms involved in alcohol-mediated host immune system dysfunction.

In this study, we determined the effects of ethyl-β-d-glucuronide (EtG), an alcohol-derived metabolite, on immune response of mice lung macrophages. We measured cytokine and chemokine production by gamma-irradiated mtb (γ-mtb) stimulated mice lung macrophages in the presence or absence of EtG. We also determined the effect of EtG on the metabolic state of γ-mtb stimulated mice lung macrophages. …

Microrna (Mirna) Complexity In Alzheimer’S Disease (Ad), Walter J. Lukiw

School of Medicine Faculty Publications

AD is a complex, progressive, age-related neurodegenerative disorder representing the most common cause of senile dementia and neurological dysfunction in our elderly domestic population. The widely observed heterogeneity of AD is a reflection of the complexity of the AD process itself and the altered molecular-genetic mechanisms operating in the diseased human brain and CNS. One of the key players in this complex regulation of gene expression in human pathological neurobiology are microRNAs (miRNAs) that, through their actions, shape the transcriptome of brain cells that normally associate with very high rates of genetic activity, gene transcription and messenger RNA (mRNA) generation. …

Target Cell-Specific Synaptic Dynamics Of Excitatory To Inhibitory Neuron Connections In Supragranular Layers Of Human Neocortex, Thomas Chartrand, Nikolas L Jorstad, Joseph T Mahoney, Michael J Taormina, Brian Long, Katherine Baker, Trygve E Bakken, Luke Campagnola, Tamara Casper, Michael Clark, Nick Dee, Florence D'Orazi, Clare Gamlin, Brian E Kalmbach, Sara Kebede, Brian R Lee, Lindsay Ng, Jessica Trinh, Charles Cobbs, Ryder P Gwinn, C Dirk Keene, Andrew L Ko, Jeffrey G Ojemann, Daniel L Silbergeld, Staci A Sorensen, Jim Berg, Kimberly A Smith, Philip R Nicovich, Tim Jarsky, Hongkui Zeng, Jonathan T Ting, Boaz P Levi, Ed Lein

Faculty, Staff and Student Publications

Rodent studies have demonstrated that synaptic dynamics from excitatory to inhibitory neuron types are often dependent on the target cell type. However, these target cell-specific properties have not been well investigated in human cortex, where there are major technical challenges in reliably obtaining healthy tissue, conducting multiple patch-clamp recordings on inhibitory cell types, and identifying those cell types. Here, we take advantage of newly developed methods for human neurosurgical tissue analysis with multiple patch-clamp recordings, post-hoc fluorescent in situ hybridization (FISH), machine learning-based cell type classification and prospective GABAergic AAV-based labeling to investigate synaptic properties between pyramidal neurons and PVALB- …

Glial Progenitor Heterogeneity And Key Regulators Revealed By Single-Cell Rna Sequencing Provide Insight To Regeneration In Spinal Cord Injury, Simranjit Singh, Andrew Rolfe, Juan J Herrera, Philip J Horner, Jia Qian Wu

Faculty, Staff and Student Publications

Recent studies have revealed the heterogeneous nature of astrocytes; however, how diverse constituents of astrocyte-lineage cells are regulated in adult spinal cord after injury and contribute to regeneration remains elusive. We perform single-cell RNA sequencing of GFAP-expressing cells from sub-chronic spinal cord injury models and identify and compare with the subpopulations in acute-stage data. We find subpopulations with distinct functional enrichment and their identities defined by subpopulation-specific transcription factors and regulons. Immunohistochemistry, RNAscope experiments, and quantification by stereology verify the molecular signature, location, and morphology of potential resident neural progenitors or neural stem cells in the adult spinal cord before …

Enhanced Evasion Of Neutralizing Antibody Response By Omicron Xbb15, Ch11, And Ca31 Variants, Panke Qu, Julia N Faraone, John P Evans, Yi-Min Zheng, Claire Carlin, Patrick Stevens, Daniel Jones, Ashish R Panchal, Linda J Saif, Eugene M Oltz, Baoshan Zhang, Tongqing Zhou, Kai Xu, Richard J Gumina, Shan-Lu Liu

Faculty, Staff and Student Publications

Omicron subvariants continuingly challenge current vaccination strategies. Here, we demonstrate nearly complete escape of the XBB.1.5, CH.1.1, and CA.3.1 variants from neutralizing antibodies stimulated by three doses of mRNA vaccine or by BA.4/5 wave infection, but neutralization is rescued by a BA.5-containing bivalent booster. CH.1.1 and CA.3.1 show strong immune escape from monoclonal antibody S309. Additionally, XBB.1.5, CH.1.1, and CA.3.1 spike proteins exhibit increased fusogenicity and enhanced processing compared with BA.2. Homology modeling reveals the key roles of G252V and F486P in the neutralization resistance of XBB.1.5, with F486P also enhancing receptor binding. Further, K444T/M and L452R in CH.1.1 and …

The Metabolic Profile Of Young, Watered Chickpea Plants Can Be Used As A Biomarker To Predict Seed Number Under Terminal Drought, Sarah J Purdy, David Fuentes, Purushothaman Ramamoorthy, Christopher Nunn, Brent N Kaiser

Faculty, Staff and Student Publications

Chickpea is the second-most-cultivated legume globally, with India and Australia being the two largest producers. In both of these locations, the crop is sown on residual summer soil moisture and left to grow on progressively depleting water content, finally maturing under terminal drought conditions. The metabolic profile of plants is commonly, correlatively associated with performance or stress responses, e.g., the accumulation of osmoprotective metabolites during cold stress. In animals and humans, metabolites are also prognostically used to predict the likelihood of an event (usually a disease) before it occurs, e.g., blood cholesterol and heart disease. We sought to discover metabolic …

Optimization Of The Filler-And-Binder Mixing Ratio For Enhanced Mechanical Strength Of Carbon-Carbon Composites, Ji-Hong Kim, Hye-In Hwang, Ji-Sun Im

Faculty, Staff and Student Publications

In this paper, a method for optimizing the mixing ratio of filler coke and binder for high-strength carbon-carbon composites is proposed. Particle size distribution, specific surface area, and true density were analyzed to characterize the filler properties. The optimum binder mixing ratio was experimentally determined based on the filler properties. As the filler particle size was decreased, a higher binder mixing ratio was required to enhance the mechanical strength of the composite. When the d

Microfibril-Associated Protein 5 And The Regulation Of Skin Scar Formation, Chen Han, Trevor R Leonardo, Bruna Romana-Souza, Junhe Shi, Shalyn Keiser, Mohamad Altakriti, Sammy Ferri-Borgogno, Samuel C Mok, Timothy J Koh, Seok Jong Hong, Lin Chen, Luisa A Dipietro

Faculty, Staff and Student Publications

Many factors regulate scar formation, which yields a modified extracellular matrix (ECM). Among ECM components, microfibril-associated proteins have been minimally explored in the context of skin wound repair. Microfibril-associated protein 5 (MFAP5), a small 25 kD serine and threonine rich microfibril-associated protein, influences microfibril function and modulates major extracellular signaling pathways. Though known to be associated with fibrosis and angiogenesis in certain pathologies, MFAP5's role in wound healing is unknown. Using a murine model of skin wound repair, we found that MFAP5 is significantly expressed during the proliferative and remodeling phases of healing. Analysis of existing single-cell RNA-sequencing data from …

Therapeutic Potential Of A Small-Molecule Stat3 Inhibitor In A Mouse Model Of Colitis, Prema Robinson, Kelsey Montoya, Emily Magness, Emma Rodriguez, Viviana Villalobos, Peng Yang, Thomas Kris Eckols, David John Tweardy

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) predisposes to colorectal cancer (CRC). In the current studies, we used the dextran sodium sulfate (DSS) murine model of colitis, which is widely used in preclinical studies, to determine the contribution of STAT3 to IBD. STAT3 has two isoforms: (STAT3 α; which has pro-inflammatory and anti-apoptotic functions, and STAT3β; which attenuates the effects of STAT3α). In the current study, we determined the contribution of STAT3 to IBD across all tissues by examining DSS-induced colitis in mice that express only STAT3α and in mice treated with TTI-101, a direct small-molecule inhibitor of both isoforms …

Architecture Of Androgen Receptor Pathways Amplifying Glucagon-Like Peptide-1 Insulinotropic Action In Male Pancreatic Β Cells, Weiwei Xu, M M Fahd Qadir, Daniela Nasteska, Paula Mota De Sa, Caroline M Gorvin, Charles R Evans, Evgeniy Potapenko, Rajakrishnan Veluthakal, Fiona B Ashford, Stavroula Bitsi, Jia Fan, Manika Bhondeley, Kejing Song, Venkata N Sure, Siva S V P Sakamuri, Lina Schiffer, Wandy Beatty, Rachael Wyatt, Daniel E Frigo, Xiaowen Liu, Prasad V Katakam, Wiebke Arlt, Jochen Buck, Lonny R Levin, Tony Hu, Jay Kolls, Charles F Burant, Alejandra Tomas, Matthew J Merrins, Debbie C Thurmond, Ernesto Bernal-Mizrachi, David J Hodson, Franck Mauvais-Jarvis

Faculty, Staff and Student Publications

Male mice lacking the androgen receptor (AR) in pancreatic β cells exhibit blunted glucose-stimulated insulin secretion (GSIS), leading to hyperglycemia. Testosterone activates an extranuclear AR in β cells to amplify glucagon-like peptide-1 (GLP-1) insulinotropic action. Here, we examined the architecture of AR targets that regulate GLP-1 insulinotropic action in male β cells. Testosterone cooperates with GLP-1 to enhance cAMP production at the plasma membrane and endosomes via: (1) increased mitochondrial production of CO

Progesterone From Ovulatory Menstrual Cycles Is An Important Cause Of Breast Cancer, Herjan J T Coelingh Bennink, Iman J Schultz, Marcus Schmidt, V Craig Jordan, Paula Briggs, Kristina Gemzell-Danielsson, Kirsten Kluivers, Jan Krijgh, Tommaso Simoncini, Frank Z Stanczyk, Robert D Langer

Faculty, Staff and Student Publications

Many factors, including reproductive hormones, have been linked to a woman's risk of developing breast cancer (BC). We reviewed the literature regarding the relationship between ovulatory menstrual cycles (MCs) and BC risk. Physiological variations in the frequency of MCs and interference with MCs through genetic variations, pathological conditions and or pharmaceutical interventions revealed a strong link between BC risk and the lifetime number of MCs. A substantial reduction in BC risk is observed in situations without MCs. In genetic or transgender situations with normal female breasts and estrogens, but no progesterone (P4), the incidence of BC is very low, suggesting …

Gastrulation Morphogenesis In Synthetic Systems

Faculty, Staff and Students Publications

Recent advances in pluripotent stem cell culture allow researchers to generate not only most embryonic cell types, but also morphologies of many embryonic structures, entirely in vitro. This recreation of embryonic form from naïve cells, known as synthetic morphogenesis, has important implications for both developmental biology and regenerative medicine. However, the capacity of stem cell-based models to recapitulate the morphogenetic cell behaviors that shape natural embryos remains unclear. In this review, we explore several examples of synthetic morphogenesis, with a focus on models of gastrulation and surrounding stages. By varying cell types, source species, and culture conditions, researchers have recreated …

Lateral Septum As A Melanocortin Downstream Site In Obesity Development, Jing Cai, Yanyan Jiang, Joshua Otiz-Guzman, Yong Xu, Benjamin R Arenkiel, Qingchun Tong

Faculty, Staff and Students Publications

The melanocortin pathway is well established to be critical for body-weight regulation in both rodents and humans. Despite extensive studies focusing on this pathway, the downstream brain sites that mediate its action are not clear. Here, we found that, among the known paraventricular hypothalamic (PVH) neuron groups, those expressing melanocortin receptors 4 (PVHMc4R) preferably project to the ventral part of the lateral septum (LSv), a brain region known to be involved in emotional behaviors. Photostimulation of PVHMc4R neuron terminals in the LSv reduces feeding and causes aversion, whereas deletion of Mc4Rs or disruption of glutamate release from LSv-projecting PVH neurons …

Discovery Of Phosphorylated Lantibiotics With Proimmune Activity That Regulate The Oral Microbiome, Mckinley Williams, Ruo Chen Huang, Cara Marks, Noah Fine, Chunxiang Sun, Fereshteh Younesi, Sina Zargaran, Ravi Orugunty, Thomas D Horvath, Sigmund J Haidacher, Anthony M Haag, Amarpreet Sabharwal, Boris Hinz, Michael Glogauer

Faculty, Staff and Students Publications

Lantibiotics are ribosomally synthesized and posttranslationally modified peptides (RiPPs) that are produced by bacteria. Interest in this group of natural products is increasing rapidly as alternatives to conventional antibiotics. Some human microbiome–derived commensals produce lantibiotics to impair pathogens’ colonization and promote healthy microbiomes. Streptococcus salivarius is one of the first commensal microbes to colonize the human oral cavity and gastrointestinal tract, and its biosynthesis of RiPPs, called salivaricins, has been shown to inhibit the growth of oral pathogens. Herein, we report on a phosphorylated class of three related RiPPs, collectively referred to as salivaricin 10, that exhibit proimmune activity and …

An Assessment Of How Clinicians And Staff Members Use A Diabetes Artificial Intelligence Prediction Tool: Mixed Methods Study, Winston R Liaw, Yessenia Ramos Silva, Erica G Soltero, Alex Krist, Angela L Stotts

Children’s Nutrition Research Center Staff Publications

Background: Nearly one-third of patients with diabetes are poorly controlled (hemoglobin A1c≥9%). Identifying at-risk individuals and providing them with effective treatment is an important strategy for preventing poor control.

Objective: This study aims to assess how clinicians and staff members would use a clinical decision support tool based on artificial intelligence (AI) and identify factors that affect adoption.

Methods: This was a mixed methods study that combined semistructured interviews and surveys to assess the perceived usefulness and ease of use, intent to use, and factors affecting tool adoption. We recruited clinicians and staff members from practices that manage diabetes. During …

Ca2+ Efflux Facilitated By Co-Transport Of Inorganic Phosphate Anion In The H+/Ca2+ Antiporter Yfke, Vasanthi Jayaraman

Faculty, Staff and Student Publications

Ca2+ is an important signaling messenger. In microorganisms, fungi, and plants, H+/Ca2+ antiporters (CAX) are known to play key roles in the homeostasis of intracellular Ca2+ by catalyzing its efflux across the cell membrane. Here, we reveal that the bacterial CAX homolog YfkE transports Ca2+ in two distinct modes: a low-flux H+/Ca2+ exchange mode and a high-flux mode in which Ca2+ and phosphate ions are co-transported (1:1) in exchange for H+. Coupling with phosphate greatly accelerates the Ca2+ efflux activity of YfkE. Our studies reveal that Ca2+ and phosphate bind to adjacent sites in a central translocation pathway and lead …

Symptom Duration And Resolution With Early Outpatient Treatment Of Convalescent Plasma For Coronavirus Disease 2019: A Randomized Trial, David Shade, Barry Meisenberg, Evan M Bloch, Aaron A R Tobian, Emily S Spivak, Bela Patel, Jonathan Gerber, Jay S Raval, Donald Forthal, James Paxton, Giselle Mosnaim, Shweta Anjan, Janis Blair, Edward Cachay, Judith Currier, Piyali Das, Moises Huaman, Catherine Sutcliffe, Anusha Yarava, Arturo Casadevall, David Sullivan, Daniel Hanley, Kelly A Gebo

Faculty, Staff and Students Publications

BACKGROUND: Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) reduces hospitalizations among outpatients treated early after symptom onset. It is unknown whether CCP reduces time to symptom resolution among outpatients.

METHODS: We evaluated symptom resolution at day 14 by trial arm using an adjusted subdistribution hazard model, with hospitalization as a competing risk. We also assessed the prevalence of symptom clusters at day 14 between treatments. Clusters were defined based on biologic clustering, impact on ability to work, and an algorithm.

RESULTS: Among 1070 outpatients followed up after transfusion, 381 of 538 (70.8%) receiving CCP and 381 of 532 (71.6%) receiving …

Differential Gene Expression Of Fresh Tissue And Patient-Derived Explants’ Matricellular Proteins Augment Inflammatory Breast Cancer Metastasis: The Possible Role Of Il-6 And Mcp-1, Alshaimaa Tarek, Hossam Taha Mohamed, Aya Ali El-Sharkawy, Shrouk Khalaf El-Sayed, Jon Mark Hirshon, Mohamed El-Shinawi

Faculty, Staff and Student Publications

BACKGROUND: Matricellular proteins comprising matrisome and adhesome are responsible for structure integrity and interactions between cells in the tumour microenvironment of breast cancer. Changes in the gene expression of matrisome and adhesome augment metastasis. Since inflammatory breast cancer (IBC) is characterized by high metastatic behaviour. Herein, we compared the gene expression profile of matrisome and adhesome in non-IBC and IBC in fresh tissue and ex vivo patient-derived explants (PDEs) and we also compared the secretory inflammatory mediators of PDEs in non-IBC and IBC to identify secretory cytokines participate in cross-talk between cells via interactions with matrisome and adhisome.

METHODS: Fifty …

The Role Of Extracellular Heat Shock Proteins In Cardiovascular Diseases, Yi-Ping Li

Faculty, Staff and Student Publications

In the early 1960s, heat shock proteins (HSPs) were first identified as vital intracellular proteinaceous components that help in stress physiology and reprogram the cellular responses to enable the organism's survival. By the early 1990s, HSPs were detected in extracellular spaces and found to activate gamma-delta T-lymphocytes. Subsequent investigations identified their association with varied disease conditions, including autoimmune disorders, diabetes, cancer, hepatic, pancreatic, and renal disorders, and cachexia. In cardiology, extracellular HSPs play a definite, but still unclear, role in atherosclerosis, acute coronary syndromes, and heart failure. The possibility of HSP-targeted novel molecular therapeutics has generated much interest and hope …

The Intensity Of Free Radical Processes And Chaperone Activity In The Saliva Of Patients With Type 2 Diabetes, Anna A. Cheprasova, Sergey S. Popov, Alexander N. Pashkov, Aleksei N. Verevkin, Valentina O. Mittova, Konstantin K. Shulgin

BioMedicine

Introduction: Saliva is a clinically informative biological fluid that contains many biomarkers, allowing multiple analyses to be performed. Aim: The objectives of this study were the assessment of the serum and saliva levels of biochemical parameters and intensity of free radical processes in T2DM patients and the identification of the correlation between certain criteria. Methods: This case-control study included 40 T2DM patients, which were compared with 40 healthy individuals. The levels of glucose, cholesterol triglycerides, total protein, diene conjugates, and chaperone activity were measured using the spectrophotometric method. The concentration of 8-oxo-2'-deoxyguanosine was assessed by competitive enzyme-linked immunosorbent assay. Results: …

Radial Arterial Waves For Chemotherapy- And Radiotherapy-Related Myocardial Damage Identification In Patients With Breast Cancer, Chia-Ying Lee, Daniela Yunchin Yen, Mark C. Hou, Ying-Ling Chen, Rong-Jen Shiau

BioMedicine

Introduction

Chemotherapy and radiation therapy for breast cancer cause side effects, such as cardiovascular changes, which can be monitored with echocardiography. However, more convenient methods are always encouraged. Radial arterial waves that are used to detect cardiovascular changes can be used to assist in confirming cardiovascular changes.

Aim

This retrospective study aimed to analyze the frequency and time domains of the radial artery pulse wave in patients with breast cancer to understand its effectiveness in identifying cardiovascular changes.

Methods

Patients with breast cancer were screened from the pulse examination records in

Changhua Christian Hospital and divided into the treatment and …

The Longitudinal Analysis Of Convergent Antibody Vdj Regions In Sars-Cov-2-Positive Patients Using Rna-Seq, Kate J Liu, Monika A Zelazowska, Kevin M Mcbride

Faculty, Staff and Student Publications

Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) is an ongoing pandemic that continues to evolve and reinfect individuals. To understand the convergent antibody responses that evolved over the course of the pandemic, we evaluated the immunoglobulin repertoire of individuals infected by different SARS-CoV-2 variants for similarity between patients. We utilized four public RNA-seq data sets collected between March 2020 and March 2022 from the Gene Expression Omnibus (GEO) in our longitudinal analysis. This covered individuals infected with Alpha and Omicron variants. In total, from 269 SARS-CoV-2-positive patients and 26 negative patients, 629,133 immunoglobulin heavy-chain variable region V(D)J sequences were reconstructed from …

New Actions On Actionable Mutations In Lung Cancers, Xiuning Le, Yasir Y Elamin, Jianjun Zhang

Faculty, Staff and Student Publications

Actionable mutations refer to DNA alterations that, if detected, would be expected to affect patients' response to treatments [...].

Kras-Dependency In Pancreatic Ductal Adenocarcinoma: Mechanisms Of Escaping In Resistance To Kras Inhibitors And Perspectives Of Therapy, Enrico Gurreri, Giannicola Genovese, Luigi Perelli, Antonio Agostini, Geny Piro, Giampaolo Tortora

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) is still one of the deadliest cancers in oncology because of its increasing incidence and poor survival rate. More than 90% of PDAC patients are KRAS mutated (KRASmu), with KRASG12D and KRASG12V being the most common mutations. Despite this critical role, its characteristics have made direct targeting of the RAS protein extremely difficult. KRAS regulates development, cell growth, epigenetically dysregulated differentiation, and survival in PDAC through activation of key downstream pathways, such as MAPK-ERK and PI3K-AKT-mammalian target of rapamycin (mTOR) signaling, in a KRAS-dependent manner. KRASmu induces the occurrence of acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial …

Smarcb1 Regulates A Tfcp2l1-Myc Transcriptional Switch Promoting Renal Medullary Carcinoma Transformation And Ferroptosis Resistance, Bujamin H Vokshi, Guillaume Davidson, Nassim Tawanaie Pour Sedehi, Alexandra Helleux, Marc Rippinger, Justine Gantzer, Philippe Baltzinger, Rachida Bouarich, Valeria Manriquez, Sakina Zaidi, Priya Rao, Pavlos Msaouel, Xiaoping Su, Hervé Lang, Thibault Tricard, Véronique Lindner, Didier Surdez, Jean-Emmanuel Kurtz, Franck Bourdeaut, Nizar M Tannir, Irwin Davidson, Gabriel G Malouf

Faculty, Staff and Student Publications

Renal medullary carcinoma (RMC) is an aggressive tumour driven by bi-allelic loss of SMARCB1 and tightly associated with sickle cell trait. However, the cell-of-origin and oncogenic mechanism remain poorly understood. Using single-cell sequencing of human RMC, we defined transformation of thick ascending limb (TAL) cells into an epithelial-mesenchymal gradient of RMC cells associated with loss of renal epithelial transcription factors TFCP2L1, HOXB9 and MITF and gain of MYC and NFE2L2-associated oncogenic and ferroptosis resistance programs. We describe the molecular basis for this transcriptional switch that is reversed by SMARCB1 re-expression repressing the oncogenic and ferroptosis resistance programs leading to ferroptotic …

Measuring Symptom Burden In Patients With Cancer During A Pandemic: The Md Anderson Symptom Inventory For Covid-19 Mdasi-Covid, Loretta A Williams, Meagan S Whisenant, Tito R Mendoza, Angela E Peek, Donna Malveaux, Darcy A Ponce, Ajay Sheshadri, Katherine A Hutcheson, Sara M Ali, Susan K Peterson, John V Heymach, Charles S Cleeland, Ishwaria M Subbiah

Faculty, Staff and Student Publications

BACKGROUND: Symptom expression in SARS-CoV-2 infection (COVID-19) may affect patients already symptomatic with cancer. Patient-reported outcomes (PROs) can describe symptom burden during the acute and postacute stages of COVID-19 and support risk stratification for levels of care. At the start of the COVID-19 pandemic, our purpose was to rapidly develop, launch through an electronic patient portal, and provide initial validation for a PRO measure of COVID-19 symptom burden in patients with cancer.

METHODS: We conducted a CDC/WHO web-based scan for COVID-19 symptoms and a relevance review of symptoms by an expert panel of clinicians treating cancer patients with COVID-19 to …

An Unknown Essential Function Of Trna Splicing Endonuclease Is Linked To The Integrated Stress Response And Intron Debranching

Faculty, Staff and Student Publications

tRNA splicing endonuclease (TSEN) has a well-characterized role in transfer RNA (tRNA) splicing but also other functions. For yeast TSEN, these other functions include degradation of a subset of mRNAs that encode mitochondrial proteins and an unknown essential function. In this study, we use yeast genetics to characterize the unknown tRNA-independent function(s) of TSEN. Using a high-copy suppressor screen, we found that sen2 mutants can be suppressed by overexpression of SEN54. This effect was seen both for tRNA-dependent and tRNA-independent functions indicating that SEN54 is a general suppressor of sen2, likely through structural stabilization. A spontaneous suppressor screen identified mutations …