Digital Commons Network^™

Targeting Calpain-2-Mediated Junctophilin-2 Cleavage Delays Heart Failure Progression Following Myocardial Infarction, Satadru K Lahiri, Jiao Lu, Yuriana Aguilar-Sanchez, Hui Li, Lucia M Moreira, Mohit M Hulsurkar, Arielys Mendoza, Mara R Turkieltaub Paredes, Jose Alberto Navarro-Garcia, Elda Munivez, Brooke Horist, Oliver M Moore, Gunnar Weninger, Sören Brandenburg, Christof Lenz, Stephan E Lehnart, Rana Sayeed, George Krasopoulos, Vivek Srivastava, Lilei Zhang, Jason M Karch, Svetlana Reilly, Xander H T Wehrens

Faculty, Staff and Students Publications

Coronary heart disease (CHD) is a prevalent cardiac disease that causes over 370,000 deaths annually in the USA. In CHD, occlusion of a coronary artery causes ischemia of the cardiac muscle, which results in myocardial infarction (MI). Junctophilin-2 (JPH2) is a membrane protein that ensures efficient calcium handling and proper excitation-contraction coupling. Studies have identified loss of JPH2 due to calpain-mediated proteolysis as a key pathogenic event in ischemia-induced heart failure (HF). Our findings show that calpain-2-mediated JPH2 cleavage yields increased levels of a C-terminal cleaved peptide (JPH2-CTP) in patients with ischemic cardiomyopathy and mice with experimental MI. We created …

Molecular Detection Of Intestinal Parasites In A Rural Community Of Colombia: A One Health Approach To Explore Potential Environmental-Zoonotic Transmission, Sergio Castañeda, Claudia Patricia Acosta, Luis Reinel Vasquez-A, Luz H Patiño, Rojelio Mejía, Juan David Ramírez

Faculty, Staff and Students Publications

Aims: Protozoan and helminth parasitic infections pose significant public health challenges, especially in developing countries with rural populations marked by suboptimal hygiene practices and socio-economic constraints. The parasites are the etiological agents of these infections and have a notably elevated global prevalence. Therefore, this study focuses on estimating the frequency and transmission dynamics of several parasitic species, including Blastocystis, Giardia, Cryptosporidium spp., Entamoeba histolytica, Ascaris lumbricoides, Trichuris trichiura, Taenia spp. and hookworms, within a rural community in southwest Colombia with a particular emphasis on the One Health framework, considering environmental and zoonotic transmission potentials.

Methods and results: This study involved …

Anti-Inflammatory And Anti-(Lymph)Angiogenic Properties Of An Abcb5+ Limbal Mesenchymal Stem Cell Population, Berbang Meshko, Thomas L. A. Volatier, Johanna Mann, Mark A. Kluth, Christoph Ganss, Markus H. Frank, Natasha Y. Frank, Bruce R. Ksander, Claus Cursiefen, Maria Notara

Research outputs 2022 to 2026

Corneal transparency and avascularity are essential for vision. The avascular cornea transitions into the vascularized conjunctiva at the limbus. Here, we explore a limbal stromal cell sub-population that expresses ABCB5 and has mesenchymal stem cell characteristics. Human primary corneal stromal cells were enriched for ABCB5 by using FACS sorting. ABCB5+ cells expressed the MSC markers CD90, CD73, and CD105. ABCB5+ but not ABCB5− cells from the same donor displayed evidence of pluripotency with a significantly higher colony-forming efficiency and the ability of trilineage differentiation (osteogenic, adipogenic, and chondrogenic). The ABCB5+ cell secretome demonstrated lower levels of the pro-inflammatory protein MIF …

Optimal Humanized Scg3-Neutralizing Antibodies For Anti-Angiogenic Therapy Of Diabetic Retinopathy, Chengchi Huang, Prabuddha Waduge, Avinash Kaur, Hong Tian, Christina Y Weng, John Timothy Stout, Iok-Hou Pang, Keith A Webster, Wei Li

Faculty, Staff and Students Publications

Secretogranin III (Scg3) is a diabetic retinopathy (DR)-restricted angiogenic factor identified in preclinical studies as a target for DR therapy. Previously, our group generated and characterized ML49.3, an anti-Scg3 monoclonal antibody (mAb) which we then converted into an EBP2 humanized antibody Fab fragment (hFab) with potential for clinical application. We also generated anti-Scg3 mT4 mAb and related EBP3 hFab. In this study, to identify the preferred hFab for DR therapy, we compared all four antibodies for binding, neutralizing and therapeutic activities in vitro and in vivo. Octet binding kinetics analyses revealed that ML49.3 mAb, EBP2 hFab, mT4 mAb and EBP3 …

Death-Associated Protein Kinase 3 Modulates Migration And Invasion Of Triple-Negative Breast Cancer Cells, Junkai Wang, Anh M Tran-Huynh, Beom-Jun Kim, Doug W Chan, Matthew V Holt, Diana Fandino, Xin Yu, Xiaoli Qi, Jin Wang, Weijie Zhang, Yi-Hsuan Wu, Meenakshi Anurag, Xiang H F Zhang, Bing Zhang, Chonghui Cheng, Charles E Foulds, Matthew J Ellis

Faculty, Staff and Students Publications

Sixteen patient-derived xenografts (PDXs) were analyzed using a mass spectrometry (MS)-based kinase inhibitor pull-down assay (KIPA), leading to the observation that death-associated protein kinase 3 (DAPK3) is significantly and specifically overexpressed in the triple-negative breast cancer (TNBC) models. Validation studies confirmed enrichment of DAPK3 protein, in both TNBC cell lines and tumors, independent of mRNA levels. Genomic knockout of DAPK3 in TNBC cell lines inhibited in vitro migration and invasion, along with down-regulation of an epithelial–mesenchymal transition (EMT) signature, which was confirmed in vivo. The kinase and leucine-zipper domains within DAPK3 were shown by a mutational analysis to be essential …

Psychosocial Outcomes Of Pain And Pain Management In Adults With Osteogenesis Imperfecta: A Qualitative Study, Whitney S Shepherd, Andrew D Wiese, Hannah E Cho, W Conor Rork, M Usman Baig, Kristin M Kostick, Dianne Nguyen, Erin M Carter, Members Of The Bbdc, Chaya N Murali, Marie-Eve Robinson, Sophie C Schneider, Brendan Lee, V Reid Sutton, Eric A Storch

Faculty, Staff and Students Publications

Objectives

Osteogenesis imperfecta (OI) is a genetic disorder characterized by bone fragility and fractures, short stature, dental abnormalities, hearing loss, scoliosis, and chronic pain. Despite a growing literature on the functional outcomes of OI, limited research has explicitly examined the psychosocial outcomes of pain within OI.

Methods

Adults with OI (N=15) were interviewed to understand pain-related experiences through a thematic analysis of semi-structured interview data. Research team members, genetic research experts, and OI clinicians developed an interview guide focused on topics related to pain and mental health challenges. Participants’ transcripts were coded by two independent coders; codes were then merged …

Enterococcus Faecalis-Derived Adenine Enhances Enterohaemorrhagic Escherichia Coli Type 3 Secretion System-Dependent Virulence, Fernando H Martins, Thibaut Rosay, Anubama Rajan, Hannah E Carter, Tayah Turocy, Andres Mejia, Jason M Crawford, Anthony W Maresso, Vanessa Sperandio

Faculty, Staff and Students Publications

Interactions between microbiota and enteric pathogens can promote colonization resistance or enhance pathogenesis. The pathobiont Enterococcus faecalis increases enterohaemorrhagic E. coli (EHEC) virulence by upregulating Type 3 Secretion System (T3SS) expression, effector translocation, and attaching and effacing (AE) lesion formation on enterocytes, but the mechanisms underlying this remain unknown. Using co-infection of organoids, metabolomics, supplementation experiments and bacterial genetics, here we show that co-culture of EHEC with E. faecalis increases the xanthine-hypoxanthine pathway activity and adenine biosynthesis. Adenine or E. faecalis promoted T3SS gene expression, while transcriptomics showed upregulation of adeP expression, which encodes an adenine importer. Mechanistically, adenine relieved …

Initiation Of Metformin In Early Pregnancy Results In Fetal Bioaccumulation, Growth Restriction, And Renal Dysmorphology In A Primate Model, Erin Bolte, Tyler Dean, Brandon Garcia, Maxim D Seferovic, Kristin Sauter, Gwendolynn Hummel, Matthew Bucher, Feng Li, John Hicks, Xuan Qin, Melissa A Suter, Enrico R Barrozo, Michael Jochum, Cynthia Shope, Jacob E Friedman, Maureen Gannon, Stephanie R Wesolowski, Carrie E Mccurdy, Paul Kievit, Kjersti M Aagaard

Faculty, Staff and Students Publications

Background: In recent years, pragmatic metformin use in pregnancy has stretched to include prediabetes mellitus, type 2 diabetes mellitus, gestational diabetes mellitus, and (most recently) preeclampsia. However, with its expanded use, concerns of unintended harm have been raised.

Objective: This study developed an experimental primate model and applied ultrahigh performance liquid chromatography coupled to triple-quadrupole mass spectrometry for direct quantitation of maternal and fetal tissue metformin levels with detailed fetal biometry and histopathology.

Study design: Within 30 days of confirmed conception (defined as early pregnancy), 13 time-bred (timed-mated breeding) Rhesus dams with pregnancies designated for fetal necropsy were initiated on …

Loss Of Tyrosine 211 Phosphorylation Of Proliferating Cell Nuclear Antigen (Pcna) Enhances Postnatal Mammary Gland Development, Yi-Chun Shen, You-Zhe Lin, Wan-Rong Wu, Pei-Le Lin, Chien-Ching Liao, Feng-Chi Chung, Chia-Yun Chen, Ching-Yu Weng, Shao-Chun Wang

BioMedicine

The intricately orchestrated progression of mammary tissue development involves the precise coordination of gland differentiation and cellular proliferation. Nevertheless, the understanding of the role and regulatory mechanisms governing the DNA replication machinery in mammary gland development remains limited. Given the essential role of DNA replication in the viability of living cells, any genetic disturbance to its replicative function, in any form, will impede organ development. This circumstance poses a technical challenge in elucidating the potential function of cell proliferation in mammary morphogenesis. PCNA is crucial in DNA replication, playing a pivotal role in the development of complete eukaryotic organisms. The …

Inhibition Of Ulk1/2 And Kras G12c Controls Tumor Growth In Preclinical Models Of Lung Cancer, Phaedra C Ghazi, Kayla T O'Toole, Sanjana Srinivas Boggaram, Michael T Scherzer, Mark R Silvis, Yun Zhang, Madhumita Bogdan, Bryan D Smith, Guillermina Lozano, Daniel L Flynn, Eric L Snyder, Conan G Kinsey, Martin Mcmahon

Faculty, Staff and Student Publications

Mutational activation of KRAS occurs commonly in lung carcinogenesis and, with the recent U.S. Food and Drug Administration approval of covalent inhibitors of KRASG12C such as sotorasib or adagrasib, KRAS oncoproteins are important pharmacological targets in non-small cell lung cancer (NSCLC). However, not all KRASG12C-driven NSCLCs respond to these inhibitors, and the emergence of drug resistance in those patients who do respond can be rapid and pleiotropic. Hence, based on a backbone of covalent inhibition of KRASG12C, efforts are underway to develop effective combination therapies. Here, we report that the inhibition of KRASG12C signaling increases autophagy in KRASG12C-expressing lung cancer …

Adenovirus Vaccine Targeting Kinases Induces Potent Antitumor Immunity In Solid Tumors, Fei Zhu, Zheng Lu, Wenjing Tang, Guangya Zhao, Yingxiang Shao, Bowen Lu, Jiage Ding, Yanyan Zheng, Lin Fang, Huizhong Li, Gang Wang, Renjin Chen, Junnian Zheng, Dafei Chai

Faculty, Staff and Students Publications

BACKGROUND: Targeting kinases presents a potential strategy for treating solid tumors; however, the therapeutic potential of vaccines targeting kinases remains uncertain.

METHODS: Adenovirus (Ad) vaccines encoding Aurora kinase A (AURKA) or cyclin-dependent kinase 7 (CDK7) were developed, and their therapeutic potentials were investigated by various methods including western blot, flow cytometry, cytotoxic T lymphocyte assay, and enzyme-linked immunospot (ELISpot), in mouse and humanized solid tumor models.

RESULTS: Co-immunization with Ad-AURKA/CDK7 effectively prevented subcutaneous tumor growth in the Renca, RM-1, MC38, and Hepa1-6 tumor models. In therapeutic tumor models, Ad-AURKA/CDK7 treatment impeded tumor growth and increased immune cell infiltration. Administration of …

Neutralization Escape, Infectivity, And Membrane Fusion Of Jn1-Derived Sars-Cov-2 Slip, Flirt, And Kp2 Variants, Pei Li, Julia N Faraone, Cheng Chih Hsu, Michelle Chamblee, Yi-Min Zheng, Claire Carlin, Joseph S Bednash, Jeffrey C Horowitz, Rama K Mallampalli, Linda J Saif, Eugene M Oltz, Daniel Jones, Jianrong Li, Richard J Gumina, Kai Xu, Shan-Lu Liu

Faculty, Staff and Student Publications

We investigate JN.1-derived subvariants SLip, FLiRT, and KP.2 for neutralization by antibodies in vaccinated individuals, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients, or class III monoclonal antibody S309. Compared to JN.1, SLip, KP.2, and especially FLiRT exhibit increased resistance to bivalent-vaccinated and BA.2.86/JN.1-wave convalescent human sera. XBB.1.5 monovalent-vaccinated hamster sera robustly neutralize FLiRT and KP.2 but have reduced efficiency for SLip. All subvariants are resistant to S309 and show decreased infectivity, cell-cell fusion, and spike processing relative to JN.1. Modeling reveals that L455S and F456L in SLip reduce spike binding for ACE2, while R346T in FLiRT and KP.2 strengthens …

Natural Killer Cell Effector Function Is Critical For Host Defense Against Alcohol-Associated Bacterial Pneumonia, Daniel Villageliu, Kelly C. Cunningham, Deandra R. Smith, Daren L. Knoell, Mason Mandolfo, Todd A. Wyatt, Derrick R. Samuelson

Food for Health: Publications

Alcohol use is an independent risk factor for the development of bacterial pneumonia due, in part, to impaired mucus-facilitated clearance, macrophage phagocytosis, and recruitment of neutrophils. Alcohol consumption is also known to reduce peripheral natural killer (NK) cell numbers and compromise NK cell cytolytic activity, especially NK cells with a mature phenotype. However, the role of innate lymphocytes, such as NK cells during host defense against alcohol-associated bacterial pneumonia is essentially unknown. We have previously shown that indole supplementation mitigates increases in pulmonary bacterial burden and improves pulmonary NK cell recruitment in alcohol-fed mice, which were dependent on aryl hydrocarbon …

Non-Coding Rnas In Peritoneal Carcinomatosis: From Bench To Bedside, Julia Bohosova, Nida Sarosh Ashraf, Ondrej Slaby, George A Calin

Faculty, Staff and Student Publications

Peritoneal carcinomatosis represents an advanced stage of tumors within the peritoneal cavity. Once considered an incurable terminal cancer metastasis, contemporary medicine is on the hunt for certain potentially curative options alongside the present day’s palliative disease management. However, for most patients, peritoneal carcinomatosis continues to pose a fatal late-stage prognosis with a grim future outlook. Over the past two decades, non-coding RNAs have garnered significant attention due to their undeniable significance in regulating cellular processes across all levels. Disruption of the intricate regulation led by non-coding RNAs has been demonstrated to have a substantial impact on various human diseases, particularly …

Early Rhombic Lip Protogenin+Ve Stem Cells In A Human-Specific Neurovascular Niche Initiate And Maintain Group 3 Medulloblastoma, Abhirami Visvanathan, Olivier Saulnier, Chuan Chen, Parthiv Haldipur, Wilda Orisme, Alberto Delaidelli, Seungmin Shin, Jake Millman, Andrew Bryant, Namal Abeysundara, Xujia Wu, Liam D Hendrikse, Vikas Patil, Zahedeh Bashardanesh, Joseph Golser, Bryn G Livingston, Takuma Nakashima, Yusuke Funakoshi, Winnie Ong, Alexandra Rasnitsyn, Kimberly A Aldinger, Cory M Richman, Randy Van Ommeren, John J Y Lee, Michelle Ly, Maria C Vladoiu, Kaitlin Kharas, Polina Balin, Anders W Erickson, Vernon Fong, Jiao Zhang, Raúl A Suárez, Hao Wang, Ning Huang, Jonelle G Pallota, Tajana Douglas, Joonas Haapasalo, Ferechte Razavi, Evelina Silvestri, Olga Sirbu, Samantha Worme, Michelle M Kameda-Smith, Xiaochong Wu, Craig Daniels, Antony K Michaelraj, Aparna Bhaduri, Daniel Schramek, Hiromichi Suzuki, Livia Garzia, Nabil Ahmed, Claudia L Kleinman, Lincoln D Stein, Peter Dirks, Christopher Dunham, Nada Jabado, Jeremy N Rich, Wei Li, Poul H Sorensen, Robert J Wechsler-Reya, William A Weiss, Kathleen J Millen, David W Ellison, Dimiter S Dimitrov, Michael D Taylor

Faculty, Staff and Students Publications

We identify a population of PRTG+ve MYChigh NESTINlow stem cells in the four-week-old human embryonic hindbrain that subsequently localizes to the ventricular zone of the rhombic lip (RLVZ). Oncogenic transformation of early Prtg+ve rhombic lip stem cells initiate Group 3 Medulloblastoma (Gr3-MB)-like tumors. PRTG+ve stem-cells grow adjacent to a human specific interposed vascular plexus in the RLVZ, a phenotype which is recapitulated in Gr3-MB, but not other types of medulloblastoma. Co-culture of Gr3-MB with endothelial cells promotes tumor stem-cell growth, with the endothelial cells adopting an immature phenotype. Targeting the PRTGhigh compartment of Gr3-MB in vivo using either the diphtheria …

Comparing Visualization Performance Of Liquid Embolic Agents Using A Novel Injectable Phantom, J Ryan Mason, Cristina Dodge, Adam Beardsley, Susan Hilsenbeck, Goetz Benndorf

Center for Medical Ethics and Health Policy Staff Publications

Background: Radiographic visualization of liquid embolic agents (LEAs) during embolization procedures in neurovascular territory represents a crucial feature to ensure efficacy and safety for the patients during endovascular treatment of arteriovenous shunting lesions. Radiopacity of available LEAs varies significantly and limited methods are currently available for comparison. The purpose of this study was to compare the contrast resolution (CR) during injection under blank roadmap of various LEAs, as well as standard contrast material.

Methods: An injectable angiographic phantom was designed consisting of parallel tubings between 313 and 1000 micron. Under roadmap, eight radiopaque liquid agents were injected and analyzed: Onyx18®, …

Evaluation Of Open-Source Ciliary Analysis Software In Primary Ciliary Dyskinesia: A Comparative Assessment, Zachary J Demetriou, José Muñiz-Hernández, Gabriel Rosario-Ortiz, Frances M Quiñones, Gabriel Gonzalez-Diaz, Marcos J Ramos-Benitez, Ricardo A Mosquera, Wilfredo De Jesús-Rojas

Faculty, Staff and Student Publications

Primary Ciliary Dyskinesia (PCD) is a rare genetic disorder characterized by alterations in motile cilia function. The diagnosis of PCD is challenging due to the lack of standardized methods in clinical practice. High-speed video microscopy analysis (HSVA) directly evaluates ciliary beat frequency (CBF) in PCD. Recently, open-source ciliary analysis software applications have shown promise in measuring CBF accurately. However, there is limited knowledge about the performance of different software applications, creating a gap in understanding their comparative effectiveness in measuring CBF in PCD. We compared two open-source software applications, CiliarMove (v219) and Cilialyzer (v1.2.1-b3098cb), against the manual count method. We …

Impact Of Cyp1a2 Genotypes On The Ergogenic Effects And Subjective Mood States Of Caffeine Ingestion In Resistance-Trained Women, Jessica M Prather, Christine M Florez, Amie Vargas, Bella Soto, Audrey Ross, Abby Harrison, Ariane H Secrest, Darryn S Willoughby, Sydney Kutter, Lem W Taylor

Faculty, Staff and Students Publications

Caffeine’s metabolism is determined by CYP1A2 genotypes: AC/CC (SLOW) and AA (FAST). This trial evaluated CYP1A2 genotypes’ impact on exercise and cognitive effects in 36 resistance-trained females assessed under placebo (PL) and caffeine (6 mg/kg bw anhydrous caffeine-CAF) conditions, before ingestion and throughout the session. 23andMe® (San Francisco, CA, USA) determined genotypes using saliva. Data were analyzed using two-way RMANOVA and paired-samples t-tests (p < 0.05). A significant main effect for genotype existed for leg press repetitions to failure (RTF) for CAF (p = 0.038), with the FAST group performing more repetitions than the SLOW (p = 0.027). There was a significant condition x genotype interaction for the subjective outcome index score (p = …

Intouch Week Of August 19, 2024, New York Medical College

InTouch

• NYMC Forms Academic Affiliation with Mount Sinai Medical Center in Miami Beach
• Making Strides Against Obesity
• From the Collection of Edward C. Halperin, M.D., M.A.
• Chancellor Halperin Hosts Virtual Town Hall Meeting
• Srihari S. Naidu, M.D., Raises Awareness About HCM Through New Children's Book
• Student Spotlight: Identical Twins Esther and Elisheva Miller Share a Dream in Medicine

The Experience Of Homelessness And Its Effects On Gut Eubiosis, Kamerin Villagomez

University Honors Theses

Microorganisms which populate the human gastrointestinal tract (GIT) have a profound effect on overall human health. The relationship between host health and eubiosis, or balance, of the GIT microbiome is symbiotic and can have reciprocal relationships with quality of sleep, quality of diet, stress and mental health, and the experience of pain. These specific aspects of health are unique in populations experiencing homelessness due to the multi-dimensional and complex nature of their lived experience. Very few studies explore populations experiencing homelessness, with even fewer investigating the intersection between this population and the human GIT microbiome. It is important to do …

Injectable, Reversibly Thermoresponsive Captopril-Laden Hydrogel For The Local Treatment Of Sensory Loss In Diabetic Neuropathy, Amit Chandra Das, James M Nichols, Caitlin V Crelli, Lu Liu, Riddhi Vichare, Hoang Vu Pham, Caitlyn M Gaffney, Fisher R Cherry, Peter M Grace, Andrew J Shepherd, Jelena M Janjic

Faculty, Staff and Student Publications

A major and irreversible complication of diabetes is diabetic peripheral neuropathy (DPN), which can lead to significant disability and decreased quality of life. Prior work demonstrates the peptide hormone Angiotensin II (Ang II) is released locally in neuropathy and drives inflammation and impaired endoneurial blood flow. Therefore, we proposed that by utilizing a local thermoresponsive hydrogel injection, we could deliver inhibitors of angiotensin-converting enzyme (ACE) to suppress Ang II production and reduce nerve dysfunction in DPN through local drug release. The ACE inhibitor captopril was encapsulated into a micelle, which was then embedded into a reversibly thermoresponsive pluronics-based hydrogel matrix. …

Preventive Effects Of Quercetin On The Leaky Gut By Suppression Of Il-1beta-Induced Transcription Factors Involved In An Inflammatory Pathway In Colonic Epithelial Cells, Wannaporn Chayalak, Sumpun Thammacharoen, Chatsri Deachapunya, Sutthasinee Poonyachoti

The Thai Journal of Veterinary Medicine

Flavonol quercetin (Q), found in vegetables and fruits, demonstrates the most potent anti-inflammatory effect. The preventive effect and cellular mechanisms of Q (Q1, Q10, and Q100 µM) on IL-1β induced leaky gut via the signaling molecules of inflammatory pathway, NF-κB p65-iκB/or p38/ERK1/2/MLCK/phospho(p)-MLC were investigated in Caco-2 cells. The cytotoxic effect of Q was initially determined by MTT assay. Transepithelial electrical resistance (TER) and apical-to-basolateral fluorescein isothiocyanate-labeled dextran (FD-4) flux were used to determine paracellular permeability. The protein expression of signaling molecules was examined by Western blot analysis, and their target MLCK mRNA expression was determined using real-time PCR. All Q …

Epigenetic Mechanisms Differentially Regulate Blood Pressure And Renal Dysfunction In Male And Female Npr1 Haplotype Mice, Prerna Kumar, Kandasamy Neelamegam, Chandramohan Ramasamy, Ramachandran Samivel, Huijing Xia, Daniel R. Kapusta, Kailash N. Pandey

School of Graduate Studies Faculty Publications

We determined the epigenetic mechanisms regulating mean arterial pressure (MAP) and renal dysfunction in guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) gene-targeted mice. The Npr1 (encoding NPRA) gene-targeted mice were treated with class 1 specific histone deacetylase inhibitor (HDACi) mocetinostat (MGCD) to determine the epigenetic changes in a sex-specific manner. Adult male and female Npr1 haplotype (1-copy; Npr1+/−), wild-type (2-copy; Npr1+/+), and gene-duplicated heterozygous (3-copy; Npr1++/+) mice were intraperitoneally injected with MGCD (2 mg/kg) for 14 days. BP, renal function, histopathology, and epigenetic changes were measured. One-copy male mice showed significantly increased MAP, renal dysfunction, and fibrosis than 2-copy and 3-copy mice. …

Factors Associated With Elevated Sars-Cov-2 Immune Response In Children And Adolescents, Sarah E Messiah, Rhiana Abbas, Emma Bergqvist, Harold W Kohl, Michael D Swartz, Yashar Talebi, Rachit Sabharwal, Haoting Han, Melissa A Valerio-Shewmaker, Stacia M Desantis, Ashraf Yaseen, Henal A Gandhi, Ximena Flandes Amavisca, Jessica A Ross, Lindsay N Padilla, Michael O Gonzalez, Leqing Wu, Mark A Silberman, David Lakey, Jennifer A Shuford, Stephen J Pont, Eric Boerwinkle

Faculty, Staff and Student Publications

BACKGROUND: Understanding the distinct immunologic responses to SARS-CoV-2 infection among pediatric populations is pivotal in navigating the COVID-19 pandemic and informing future public health strategies. This study aimed to identify factors associated with heightened antibody responses in children and adolescents to identify potential unique immune dynamics in this population.

METHODS: Data collected between July and December 2023 from the Texas Coronavirus Antibody REsponse Survey (Texas CARES), a statewide prospective population-based antibody survey among 1-to-19-year-old participants, were analyzed. Each participant had the following data available for analysis: (1) Roche Elecsys® Anti-SARS-CoV-2 Immunoassay for Nucleocapsid protein antibodies (Roche N-test), (2) qualitative and …

Chatgpt And Google Assistant As A Source Of Patient Education For Patients With Amblyopia: Content Analysis, Gloria Wu, David A Lee, Weichen Zhao, Adrial Wong, Rohan Jhangiani, Sri Kurniawan

Faculty, Staff and Student Publications

Background: We queried ChatGPT (OpenAI) and Google Assistant about amblyopia and compared their answers with the keywords found on the American Association for Pediatric Ophthalmology and Strabismus (AAPOS) website, specifically the section on amblyopia. Out of the 26 keywords chosen from the website, ChatGPT included 11 (42%) in its responses, while Google included 8 (31%).

Objective: Our study investigated the adherence of ChatGPT-3.5 and Google Assistant to the guidelines of the AAPOS for patient education on amblyopia.

Methods: ChatGPT-3.5 was used. The four questions taken from the AAPOS website, specifically its glossary section for amblyopia, are as follows: (1) What …

In Vitro Antibacterial, Antibiofilm Activities, And Phytochemical Properties Of Posidonia Oceanica (L) Delile: An Endemic Mediterranean Seagrass, Ertugrul Ozbil, Mehmet Ilktac, Sultan Ogmen, Ovgu Isbilen, Jesus M Duran Ramirez, Jana Gomez, Jennifer N Walker, Ender Volkan

Faculty, Staff and Student Publications

In the antibiotic resistance era, utilizing understudied sources for novel antimicrobials or antivirulence agents can provide new advances against antimicrobial resistant pathogens. In this study, we aimed to investigate antibacterial and antibiofilm activities of Posidonia oceanica (L.) Delile against Enterococcus faecalis ATCC 29212, Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922 and Klebsiella pneumoniae ATCC 700603 and several S. aureus clinical isolates obtained from medical devices, including patient urinary catheters and breast implant infections, with varying antibiotic recalcitrance profiles. The ethanolic and methanolic extracts from P. oceanica rhizome exhibited significant antibacterial activity against E. faecalis and S. aureus, as well …

Persistence Of Daptomycin-Resistant And Vancomycin-Resistant Enterococci In Hospitalized Patients With Underlying Malignancies: A 7-Year Follow-Up Study, Lynn El Haddad, Georgios Angelidakis, Yuting Zhai, Layale Yaghi, Cesar A Arias, Samuel A Shelburne, Kwangcheol Casey Jeong, Roy F Chemaly

Faculty, Staff and Student Publications

Vancomycin-resistant enterococci (VRE) commonly colonize the gut of individuals with hematologic malignancies or undergoing hematopoietic cell transplant (HCT) and may cause bacteremia. In 2012, we identified VRE isolates from patients and patients' rooms and showed transmission networks of highly genetically related daptomycin-resistant (DR)-VRE strains. This is a follow-up study performing whole-genome sequencing (WGS) and phylogenetic analyses on 82 clinical VRE strains isolated from stools and blood cultures of patients with leukemia and HCT between 2015 and 2019. Here, we observed transmission of highly genetically related strains between rooms on the same or on different floors, including a DR-VRE strain identified …

Regulatory Complexity Of Cellular Differentiation In Candida Albicans Revealed Through Systematic Screening Of Protein Kinase Mutants, Michael C Lorenz

Faculty, Staff and Student Publications

A recent study in mBio reports the construction and preliminary screening of a library containing mutants of 99 of the 119 predicted protein kinases in Candida albicans (the majority of the remaining 20 are probably essential) (J. Kramara, M.-J. Kim, T. L. Ollinger, L. C. Ristow, et al., mBio e01249-24, 2024, https://doi.org/10.1128/mbio.01249-24). Using a quantitative competition assay in 10 conditions that represent nutritional, osmotic, cell wall, and pH stresses that are considered to model various aspects of the host environment allowed them to phenotypically cluster kinases, which highlight both the integration and specialization of signaling pathways, suggesting novel functions …

Infant And Adult Human Intestinal Enteroids Are Morphologically And Functionally Distinct, Grace O Adeniyi-Ipadeola, Julia D Hankins, Amal Kambal, Xi-Lei Zeng, Ketki Patil, Victoria Poplaski, Carolyn Bomidi, Hoa Nguyen-Phuc, Sandra L Grimm, Cristian Coarfa, Fabio Stossi, Sue E Crawford, Sarah E Blutt, Allison L Speer, Mary K Estes, Sasirekha Ramani

Faculty, Staff and Students Publications

UNLABELLED: Human intestinal enteroids (HIEs) are gaining recognition as physiologically relevant models of the intestinal epithelium. While HIEs from adults are used extensively in biomedical research, few studies have used HIEs from infants. Considering the dramatic developmental changes that occur during infancy, it is important to establish models that represent infant intestinal characteristics and physiological responses. We established jejunal HIEs from infant surgical samples and performed comparisons to jejunal HIEs from adults using RNA sequencing (RNA-Seq) and morphologic analyses. We then validated differences in key pathways through functional studies and determined whether these cultures recapitulate known features of the infant …

Pediatric Glioma Immune Profiling Identifies Tim3 As A Therapeutic Target In Braf Fusion Pilocytic Astrocytoma, Shashwat Tripathi, Hinda Najem, Corey Dussold, Sebastian Pacheco, Ruochen Du, Moloud Sooreshjani, Lisa Hurley, James P Chandler, Roger Stupp, Adam M Sonabend, Craig M Horbinski, Rimas V Lukas, Joanne Xiu, Giselle Lopez, Theodore P Nicolaides, Valerie Brown, Nitin R Wadhwani, Sandi K Lam, Charles David James, Ganesh Rao, Maria G Castro, Amy B Heimberger, Michael Decuypere

Faculty, Staff and Students Publications

Despite being the leading cause of cancer-related childhood mortality, pediatric gliomas have been relatively understudied, and the repurposing of immunotherapies has not been successful. Whole-transcriptome sequencing, single-cell sequencing, and sequential multiplex immunofluorescence were used to identify an immunotherapeutic strategy that could be applied to multiple preclinical glioma models. MAPK-driven pediatric gliomas have a higher IFN signature relative to other molecular subgroups. Single-cell sequencing identified an activated and cytotoxic microglia (MG) population designated MG-Act in BRAF-fused, MAPK-activated pilocytic astrocytoma (PA), but not in high-grade gliomas or normal brain. T cell immunoglobulin and mucin domain 3 (TIM3) was expressed on MG-Act and …