Biological Phenomena, Cell Phenomena, and Immunity Commons^™

Identification And Catalog Of Viral Transcriptional Regulators In Human Diseases, Citu Citu, Le Chang, Astrid M Manuel, Nitesh Enduru, Zhongming Zhao

Faculty, Staff and Student Publications

Viral genomes encode viral transcriptional regulators (vTRs) that manipulate host gene expression to facilitate replication and evade immune detection. Nevertheless, their role in non-cancerous diseases remains largely underexplored. Here, we unveiled 268 new candidate vTRs from 14 of the 20 viral families we investigated. We mapped vTRs' genome-wide binding profiles and identified their potential human targets, which were enriched in immune-mediated pathways, neurodegenerative disorders, and cancers. Through vTR DNA-binding preference analysis, 283 virus-specific and human-like motifs were identified. Prioritized Epstein-Barr virus (EBV) vTR target genes were associated with multiple sclerosis (MS), rheumatoid arthritis, and systemic lupus erythematosus. The partitioned heritability …

Rare Damaging Ccr2 Variants Are Associated With Lower Lifetime Cardiovascular Risk, Marios K Georgakis, Rainer Malik, Omar El Bounkari, Natalie R Hasbani, Jiang Li, Jennifer E Huffman, Gabrielle Shakt, Reinier W P Tack, Tamara N Kimball, Yaw Asare, Alanna C Morrison, Noah L Tsao, Renae Judy, Braxton D Mitchell, Huichun Xu, May E Montasser, Ron Do, Eimear E Kenny, Ruth J F Loos, James G Terry, John Jeffrey Carr, Joshua C Bis, Bruce M Psaty, W T Longstreth, Kendra A Young, Sharon M Lutz, Michael H Cho, Jai Broome, Alyna T Khan, Fei Fei Wang, Nancy Heard-Costa, Sudha Seshadri, Ramachandran S Vasan, Nicholette D Palmer, Barry I Freedman, Donald W Bowden, Lisa R Yanek, Brian G Kral, Lewis C Becker, Patricia A Peyser, Lawrence F Bielak, Farah Ammous, April P Carson, Michael E Hall, Laura M Raffield, Stephen S Rich, Wendy S Post, Russel P Tracy, Kent D Taylor, Xiuqing Guo, Michael C Mahaney, Joanne E Curran, John Blangero, Shoa L Clarke, Jeffrey W Haessler, Yao Hu, Themistocles L Assimes, Charles Kooperberg, Jürgen Bernhagen, Christopher D Anderson, Scott M Damrauer, Ramin Zand, Jerome I Rotter, Paul S De Vries, Martin Dichgans

Faculty, Staff and Student Publications

BACKGROUND: Previous work has shown a role of CCL2, a key chemokine governing monocyte trafficking, in atherosclerosis. However, it remains unknown whether targeting CCR2, the cognate receptor of CCL2, provides protection against human atherosclerotic cardiovascular disease.

METHODS: Computationally predicted damaging or loss-of-function (REVEL > 0.5) variants within CCR2 were detected in whole-exome-sequencing data from 454,775 UK Biobank participants and tested for association with cardiovascular endpoints in gene-burden tests. Given the key role of CCR2 in monocyte mobilization, variants associated with lower monocyte count were prioritized for experimental validation. The response to CCL2 of human cells transfected with these variants was tested …

Nutritional Status, Social Determinants Of Health And Clinical Outcomes In Critically Ill Children, Yash Desai, Andrea Marroquín, Paola Hong-Zhu, Nicole Knebusch, Stephanie Vazquez, Marwa Mansour, Thomas P Fogarty, M Hossein Tcharmtchi, Fernando Stein, Jorge A Coss-Bu

Faculty, Staff and Students Publications

Introduction: Childhood malnutrition remains a risk factor for morbidity and mortality. Children admitted to the Pediatric Intensive Care Unit (PICU) are at a higher risk of worsening nutritional status with adverse clinical outcomes. The burden of malnutrition is strongly linked to various well-defined social determinants of health, including race, socioeconomic status, and geography, as these factors influence household food insecurity. This study aimed to analyze the interrelationships of nutritional status, social determinants of health, and health outcomes in critically ill children.

Methods: Retrospective cohort study of 6418 critically ill children admitted to PICU from January 2014 to December 2017. Demographic …

The Guanine Nucleotide Exchange Factor Ric-8a Regulates The Sensitivity Of Constitutively Active Gαq To The Inhibitor Ym-254890, Morgan Dwyer, Jiansong Luo, Tyson Todd, Kendall Blumer, Gregory Tall, Philip Wedegaertner

Department of Biochemistry and Molecular Biology Faculty Papers

Heterotrimeric G proteins are stimulated under normal circumstances by G protein-coupled receptors to promote downstream intracellular signaling. Mutations can occur in αq at glutamine 209 (Q209) that cause constitutive, G protein-coupled receptor independent signaling due to disruption of GTPase activity. Specifically, Q209L/P mutations are oncogenic drivers of uveal melanoma. YM-254890 (YM) has been shown to selectively inhibit both WT and constitutively active (CA) αqQ209L/P by preventing the release of GDP and exchange for GTP, thereby halting downstream signaling. Because αqQL/P are thought to be primarily GTP-bound and GTPase deficient, the current mechanistic understanding of YM inhibition needs further investigation to …

Utility Of 3-Dimensional Echocardiography In Patients With Complex Intracardiac Connections And Ventricular Septal Defects, Aura Andrea Sanchez Mejia, Tam T Doan, Christian Lilje, Minh B Nguyen, Ricardo H Pignatelli, Shagun Sachdeva, Anitha Parthiban

Faculty, Staff and Students Publications

The surgical management of patients with complex intracardiac connections, ventricular septal defect (VSD), and 2 adequately sized ventricles is challenging. Understanding the VSD anatomy and its spatial relationships with the outflow tracts is critical to determining the suitability for biventricular repair. Transthoracic 2-dimensional echocardiography (2D-echo) is the primary cardiac imaging tool in congenital heart disease. Transthoracic 3-dimensional echocardiography (3D-echo) has an additive role over 2D-echo in the definition of the potential baffle pathway from the VSD to the semilunar valves, the anatomical characteristics of the VSD, and any substrate for systemic outflow tract obstruction postrepair. In this paper, we describe …

Metabolic Signatures In Adipose Tissue Linking Lipophilic Persistent Organic Pollutant Mixtures To Blood Pressure Five Years After Bariatric Surgery Among Adolescents, Shudi Pan, Zhenjiang Li, Douglas I Walker, Brittney O Baumert, Hongxu Wang, Jesse A Goodrich, Sarah Rock, Thomas H Inge, Todd M Jenkins, Stephanie Sisley, Scott M Bartell, Stavra Xanthakos, Xiangping Lin, Brooklynn Mcneil, Anna R Robuck, Catherine E Mullins, Michele A La Merill, Erika Garcia, Max T Aung, Sandrah P Eckel, Rob Mcconnell, David V Conti, Justin R Ryder, Lida Chatzi

Faculty, Staff and Students Publications

Persistent organic pollutants (POPs) are lipophilic environmental contaminants accumulated in the adipose tissue. Weight loss interventions, such as bariatric surgery, can mobilize POPs from adipose tissue into the bloodstream. We hypothesized that this mobilization could contribute to increases in blood pressure among 57 adolescents with severe obesity undergoing bariatric surgery. POPs and metabolic features were measured from visceral adipose tissue collected during surgery using gas and liquid chromatography, coupled with high-resolution mass spectrometry. Blood pressure was assessed at baseline, 6 months, and 5 years post-surgery. We used quantile g-computation to estimate associations of POP mixtures with blood pressure changes. With …

Novel Signaling Pathways Involved In Ybx1 Role In Hepatocellular Carcinoma, Yamile Abuchard Anaya, Ana Ayala Pazzi, Dennis Kwabiah, Veerababu Nagati, Ricardo Pequeno Bracho, Kyle Doxtater, Subhash C. Chauhan, Manish K. Tripathi

Research Symposium

Background: The most prevalent type of liver cancer is hepatocellular carcinoma (HCC), and socioeconomic and health disparities have a major impact on both its incidence and fatality rates. HCC rates are typically greater in areas with poor access to healthcare, high obesity rates, and a high frequency of infectious diseases. Because of risk factors include diabetes, non-alcoholic fatty liver disease (NAFLD), and Hepatitis B and C, HCC is particularly common in the Rio Grande Valley (RGV). The burden of HCC in this underprivileged area is made worse by McAllen, Texas, which regrettably holds the distinction of being the most obese …

Dysregulation Of Cholesterol Metabolism And Sorafenib Drug Resistance In Hepatocellular Carcinoma, Veerababu Nagati, Dennis Kwabiah, Yamile Abuchard Anaya, Ana Ayala Pazzi, Manish K. Tripathi

Research Symposium

Background: Hepatocellular carcinoma (HCC) is among the most prevalent cancers and a leading cause of cancer-related deaths worldwide. Sorafenib, a multikinase inhibitor, serves as a key first-line treatment for HCC when surgical intervention is not an option. However, primary and acquired resistance to sorafenib has significantly limited its effectiveness, reducing the disease control rate. Dysregulation of numerous genes that influence cancer cell proliferation, survival, and drug resistance contributes to this challenge. Identifying the molecular drivers of sorafenib resistance remains critical to improving treatment outcomes. Several factors, including activation of oncogenic pathways (e.g., Akt/mTOR), hypoxia, cholesterol metabolism, EMT, multidrug resistance, and …

Carm1 Regulates Tubulin Autoregulation Through Pi3kc2Α R175 Methylation, Yena Cho, Jee Won Hwang, Mark T Bedford, Dae-Geun Song, Su-Nam Kim, Yong Kee Kim

Faculty, Staff and Student Publications

Tubulin is crucial in several cellular processes, including intracellular organization, organelle transport, motility, and chromosome segregation. Intracellular tubulin concentration is tightly regulated by an autoregulation mechanism, in which excess free tubulin promotes tubulin mRNA degradation. However, the details of how changes in free tubulin levels initiate this autoregulation remain unclear. In this study, we identified coactivator-associated arginine methyltransferase 1 (CARM1)-phosphatidylinositol 3-kinase class 2α (PI3KC2α) axis as a novel regulator of tubulin autoregulation. CARM1 stabilizes PI3KC2α by methylating its R175 residue. Once PI3KC2α is not methylated, it becomes unstable, leading to decreased cellular levels. Loss of PI3KC2α results in the release …

Utilidad De La Combinación De Los Biomarcadores: Procalcitonina, Proteína C Reactiva Y Volumen Plaquetario Medio En El Diagnóstico Temprano De Sepsis Neonatal [Usefulness Of The Combination Of Biomarkers: Procalcitonin, C-Reactive Protein And Mean Platelet Volume In The Early Diagnosis Of Neonatal Sepsis], Oscar Manuel Berlanga Bolado Jr, Patricia Rivera Vazquez, Arely Socorro Hernández García, Angelica Lizbeth Martinez Ortiz

Research Symposium

Introducción: La sepsis neonatal es una causa frecuente de morbilidad y mortalidad infantil. Se le ha definido como un síndrome clínico caracterizado por signos sistémicos de infección, acompañado de bacteriemia en el primer mes de vida. Por lo tanto, el diagnóstico temprano es fundamental.

Objetivo: Conocer la sensibilidad y especificidad de la combinación de biomarcadores séricos como procalcitonina, proteína C reactiva y volumen plaquetario medio en el diagnóstico temprano de sepsis neonatal.

Material y métodos: Estudio clínico, de tipo prospectivo, predictivo, observacional, analítico, longitudinal y conveniencia. Se analizaron los biomarcadores como PCT, PCR, VPM para diagnosticar sepsis neonatal. Se incluyeron …

Recovery Potential In Patients After Cardiac Arrest Who Die After Limitations Or Withdrawal Of Life Support, Jonathan Elmer, Patrick J Coppler, Cecelia Ratay, Alexis Steinberg, Sara Difiore-Sprouse, Nicholas Case, Baruch Fischhoff, Maria De-Arteaga, Alain Cariou, Alejandro A Rabinstein, Andrea O Rossetti, Ankur A Doshi, Bradley J Molyneaux, Cameron Dezfulian, Carolina B Maciel, Christoph Leithner, Cindy H Hsu, Claudio Sandroni, David M Greer, David B Seder, Francis X Guyette, Fabio Silvio Taccone, Hiromichi Naito, Jasmeet Soar, Jean-Baptiste Lascarrou, Jerry P Nolan, Karen G Hirsch, Katherine M Berg, Marion Moseby-Knappe, Markus B Skrifvars, Michael C Kurz, Min Jung Kathy Chae, Mypinder S Sekhon, Nicholas J Johnson, Pedro Kurtz, Romergryko G Geocadin, Sachin Agarwal, Teresa L May, Theresa M Olasveengen, Clifton W Callaway, Optimizing Recovery Prediction After Cardiac Arrest (Orca) Study Group

Faculty, Staff and Students Publications

Importance: Understanding the relationship between patients' clinical characteristics and outcomes is fundamental to medicine. When critically ill patients die after withdrawal of life-sustaining therapy (WLST), the inability to observe the potential for recovery with continued aggressive care could bias future clinical decisions and research.

Objective: To quantify the frequency with which experts consider patients who died after WLST following resuscitated cardiac arrest to have had recovery potential if life-sustaining therapy had been continued.

Design, setting, and participants: This prospective cohort study included comatose adult patients (aged ≥18 years) treated following resuscitation from cardiac arrest at a single academic medical center …

Abnormal Urine Drug Screens In Pregnancy- Opportunity For Laboratory Stewardship, Anil K Chokkalla, Sahil Malik, Ridwan Ibrahim, Sridevi Devaraj

Faculty, Staff and Students Publications

Background: Clinical testing for drugs of abuse typically involves initial screening followed by confirmatory testing. Due to limited evidence-based guidelines, the healthcare provider makes the decision to confirm abnormal screens based on the clinical context. This two-step approach proved to be inadequate in scenarios like maternal substance abuse and subsequent fetal/ newborn exposure. The goal of this study is to assess and improve the confirmatory testing rate of abnormal screens among pregnant patients at our women's center.

Methods: A retrospective chart review was conducted to assess the confirmation rates among positively screened pregnant patients, and a lab stewardship initiative was …

Inappropriate Laboratory Testing: Significant Waste Quantified By A Large-Scale Year-Long Study Of Medicare And Commercial Payer Reimbursement, Dave Smart, Jeff Schreier, Ila R Singh

Faculty, Staff and Students Publications

Context.—: Laboratory testing, beyond what is essential for managing health, is considered low-value care, posing patient risks and wasting resources. Measuring excess testing on a national level is crucial to identify waste and optimize healthcare resource allocation for maximum impact.

Objective.—: To measure inappropriate laboratory testing and its cost across Medicare and many US commercial payers.

Design.—: A retrospective analysis on 2019 claims data measured the frequency of 4 commonly used laboratory tests among 64 million individuals with Medicare and 168 million with commercial insurance. Tests included 25-hydroxy vitamin D, prostate-specific antigen, lipid panel, and hemoglobin A1c. Clinical guidelines, medical …

Chronic Hepatitis And Hemophagocytic Lymphohistiocytosis Associated With Systemic Chronic Active Epstein-Barr Virus Disease, Emmanuel Palomera-Tejeda, Lauren Shaffer, Michael Shi, Nagasri Shankar, Roshan Raza, George Cholankeril

Faculty, Staff and Students Publications

Systemic chronic active Epstein-Barr virus (EBV) disease is a rare, delayed, and life-threatening complication of EBV infection. It is characterized by persistent viremia and a mononucleosis-like syndrome with multisystemic involvement because of lymphocytic tissue infiltration. We present the case of an 82-year-old woman without known immunodeficiency who presented with abnormal liver enzymes and interstitial pneumonia. Investigations revealed hyperferritinemia, elevated soluble interleukin-2 receptor levels, hypofibrinogenemia, and hepatosplenomegaly, consistent with hemophagocytic lymphohistiocytosis, as well as a high EBV viral load. Liver biopsy demonstrated portal chronic lymphocytic inflammation and positive EBV in situ hybridization, suggesting systemic chronic active Epstein-Barr virus disease as the …

Should All Pediatric Patients With Type 1 Autoimmune Hepatitis Be Screened For Inflammatory Bowel Disease?, Richard Kellermayer

Faculty, Staff and Students Publications

No abstract provided.

Depletion Of Acetyl-Coa Carboxylase 1 Facilitates Epithelial-Mesenchymal Transition In Prostate Cancer Cells By Activating The Mapk/Erk Pathway, Jiarun Lai, Shaoyou Liu, Yupeng Chen, Jian Chen, Jinchuang Li, Zhenguo Liang, Xinyue Mei, Yuanfa Feng, Zhaodong Han, Funeng Jiang, Shengbang Yang, Yongding Wu, Huijing Tan, Junchen Liu, Huichan He, Weide Zhong

Faculty, Staff and Student Publications

Hyperactivation of fatty acid biosynthesis holds promise as a targeted therapeutic strategy in prostate cancer (PCa). However, inhibiting these enzymes could potentially promote metastatic progression in various other cancers. Herein, we found that depletion of acetyl-CoA carboxylase 1 (encoded by ACACA), the enzyme responsible for the first and rate-limiting step of de novo fatty acid biosynthesis, facilitated epithelial-mesenchymal transition (EMT) and migration of PCa cells. This finding was validated in vitro through cell migration assays and in vivo using a metastatic model established by tail vein injection of ACACA-depleted cells into BALB/c nude mice. Additionally, depletion of ACACA activated the …

Clostridioides Difficile Colonization Is Not Mediated By Bile Salts And Utilizes Stickland Fermentation Of Proline In An In Vitro Model, Xiaoyun Huang, April E Johnson, Joshua N Brehm, Thi Van Thanh Do, Thomas A Auchtung, Hugh C Mccullough, Armando I Lerma, Sigmund J Haidacher, Kathleen M Hoch, Thomas D Horvath, Joseph A Sorg, Anthony M Haag, Jennifer M Auchtung

Faculty, Staff and Students Publications

Treatment with antibiotics is a major risk factor for Clostridioides difficile infection, likely due to depletion of the gastrointestinal microbiota. Two microbiota-mediated mechanisms thought to limit C. difficile colonization include the conversion of conjugated primary bile salts into secondary bile salts toxic to C. difficile growth and competition between the microbiota and C. difficile for limiting nutrients. Using a continuous flow model that simulates the nutrient conditions of the distal colon, we investigated how treatment with 6 clinically used antibiotics influenced susceptibility to C. difficile infection in 12 different microbial communities cultivated from healthy individuals. Antibiotic treatment reduced microbial richness; …

Impact Of Measurable Residual Disease Clearance Kinetics In Patients With Aml Undergoing Intensive Chemotherapy, Wei-Ying Jen, Koji Sasaki, Farhad Ravandi, Tapan M Kadia, Sa A Wang, Wei Wang, Sanam Loghavi, Naval G Daver, Courtney D Dinardo, Ghayas C Issa, Hussein A Abbas, Cedric Nasnas, Alex Bataller, Samuel Urrutia, Omer S Karrar, Sherry Pierce, Hagop M Kantarjian, Nicholas J Short

Faculty, Staff and Student Publications

The prognostic impact of measurable residual disease (MRD) in acute myeloid leukemia (AML) is unequivocal; however, the optimal time point for achieving undetectable MRD is unclear. We retrospectively studied patients with newly diagnosed (ND) AML who achieved remission with frontline intensive chemotherapy and had MRD assessed by flow cytometry after induction (time point 1 [TP1]) and after cycles 2 or 3 (TP2). Cases were grouped into MRD negative (Neg)/Neg, positive (Pos)/Neg, or Pos/Pos at TP1 and TP2, respectively. Of 1980 patients with ND AML, 277 met the inclusion criteria and were included in this analysis. The median relapse-free survival (RFS) …

Bilateral Carotid Body Paragangliomas With Succinate Dehydrogenase Complex Subunit D Gene Mutation, Abdul R. Khan, Kelvin Li, Neel D. Gupta, Jagan D. Gupta, Mohammed M. Ansari, Triet M. Do, Enrique Palacios

School of Medicine Faculty Publications

No abstract provided.

Plasma Micrornas To Select Optimal Patients For Antibody Production From Anti-Addiction Vaccines, Thomas R Kosten, Amrit Koirala, David A Nielsen, Coreen B Domingo, Ynhi T Thomas, Preethi H Gunaratne, Cristian Coarfa

Faculty, Staff and Students Publications

Background: Cocaine and illicit amphetamines (disguised as “Adderall”) are being laced with fentanyl and producing accidental and intentional fatal overdoses. Vaccines can prevent these overdoses, but 33% of humans generate insufficient anti-drug antibody (AB) levels. Plasma microRNAs (miRs) can be used to predict non-responders. We have plasma stored from 152 cocaine vaccine trial participants following three vaccinations over 9 weeks and examined miRs as potential response biomarkers. Methods: We compared 2517 miRs before anti-cocaine vaccination in participants with the highest (n = 25) to the lowest (n = 23) antibody levels. False Discovery Rates (FDRs) were applied to identify differentially …