Medical Microbiology Commons^™

Systemic Interindividual Dna Methylation Variants In Cattle Share Major Hallmarks With Those In Humans, Wen-Jou Chang, Maria S Baker, Eleonora Laritsky, Chathura J Gunasekara, Uditha Maduranga, Justine C Galliou, Joseph W Mcfadden, Jessica R Waltemyer, Bruce Berggren-Thomas, Brianna N Tate, Hanxue Zhang, Benjamin D Rosen, Curtis P Van Tassell, George E Liu, Cristian Coarfa, Yi Athena Ren, Robert A Waterland

Faculty, Staff and Students Publications

BACKGROUND: We recently identified ~ 10,000 correlated regions of systemic interindividual epigenetic variation (CoRSIVs) in the human genome. These methylation variants are amenable to population studies, as DNA methylation measurements in blood provide information on epigenetic regulation throughout the body. Moreover, establishment of DNA methylation at human CoRSIVs is labile to periconceptional influences such as nutrition. Here, we analyze publicly available whole-genome bisulfite sequencing data on multiple tissues of each of two Holstein cows to determine whether CoRSIVs exist in cattle.

RESULTS: Focusing on genomic blocks with ≥ 5 CpGs and a systemic interindividual variation index of at least 20, …

Intratumoral Microbiome Of Adenoid Cystic Carcinomas And Comparison With Other Head And Neck Cancers, Tatiana V Karpinets, Yoshitsugu Mitani, Chia-Chi Chang, Xiaogang Wu, Xingzhi Song, Ivonne I Flores, Lauren K Mcdaniel, Yasmine M Hoballah, Fabiana J Veguilla, Renata Ferrarotto, Lauren E Colbert, Nadim J Ajami, Robert R Jenq, Jianhua Zhang, Andrew P Futreal, Adel K El-Naggar

Faculty, Staff and Student Publications

Adenoid cystic carcinoma (ACC) is a rare, usually slow-growing yet aggressive head and neck malignancy. Despite its clinical significance, our understanding of the cellular evolution and microenvironment in ACC remains limited. We investigated the intratumoral microbiomes of 50 ACC tumor tissues and 33 adjacent normal tissues using 16S rRNA gene sequencing. This allowed us to characterize the bacterial communities within the ACC and explore potential associations between the bacterial community structure, patient clinical characteristics, and tumor molecular features obtained through RNA sequencing. The bacterial composition in the ACC was significantly different from that in adjacent normal salivary tissue, and the …

Morgs3 Functions In Intracellular Reactive Oxygen Species Perception-Integrated Camp Signaling To Promote Appressorium Formation In Magnaporthe Oryzae, Ruiming Zhang, Xinyu Liu, Jiayun Xu, Chen Chen, Zhaoxuan Tang, Chengtong Wu, Xinyue Li, Lei Su, Muxing Liu, Leiyun Yang, Gang Li, Haifeng Zhang, Ping Wang, Zhengguang Zhang

School of Graduate Studies Faculty Publications

Regulator of G-protein signaling (RGS) proteins exhibit GTPase-accelerating protein activities to govern G-protein function. In the rice blast fungus Magnaporthe oryzae, there is a family of at least eight RGS and RGS-like proteins (MoRgs1 to MoRgs8), each exhibiting distinct or shared functions in the growth, appressorium formation, and pathogenicity. MoRgs3 recently emerged as one of the crucial regulators that senses intracellular oxidation during appressorium formation. To explore this unique regulatory mechanism of MoRgs3, we identified the nucleoside diphosphate kinase MoNdk1 that interacts with MoRgs3. MoNdk1 phosphorylates MoRgs3 under induced intracellular reactive oxygen species levels, and MoRgs3 phosphorylation is required for …

Baseline Data Collections Of Lipopolysaccharide Content In 414 Herbal Extracts And Its Role In Innate Immune Activation, Vindy Tjendana Tjhin, Masataka Oda, Masashi Yamashita, Tomoko Iwaki, Yasuko Fujita, Koji Wakame, Hiroyuki Inagawa, Gen-Ichiro Soma

Faculty, Staff and Student Publications

Some herbal extracts contain relatively high amounts of lipopolysaccharide (LPS). Because orally administered LPS activates innate immunity without inducing inflammation, it plays a role as an active ingredient in herbal extracts. However, the LPS content in herbal extracts remains extensively unevaluated. This study aimed to create a database of LPS content in herbal extracts; therefore, the LPS content of 414 herbal extracts was measured and the macrophage activation potential was evaluated. The LPS content of these hot water extracts was determined using the kinetic-turbidimetric method. The LPS concentration ranged from a few ng/g to hundreds of μg/g (Standard Escherichia coli …

A Pan-Cancer Patient-Derived Xenograft Histology Image Repository With Genomic And Pathologic Annotations Enables Deep Learning Analysis, Brian S White, Xing Yi Woo, Soner Koc, Todd Sheridan, Steven B Neuhauser, Shidan Wang, Yvonne A Evrard, Li Chen, Ali Foroughi Pour, John D Landua, R Jay Mashl, Sherri R Davies, Bingliang Fang, Maria Gabriela Raso, Kurt W Evans, Matthew H Bailey, Yeqing Chen, Min Xiao, Jill C Rubinstein, Brian J Sanderson, Michael W Lloyd, Sergii Domanskyi, Lacey E Dobrolecki, Maihi Fujita, Junya Fujimoto, Guanghua Xiao, Ryan C Fields, Jacqueline L Mudd, Xiaowei Xu, Melinda G Hollingshead, Shahanawaz Jiwani, Saul Acevedo, Pdxnet Consortium, Brandi N Davis-Dusenbery, Peter N Robinson, Jeffrey A Moscow, James H Doroshow, Nicholas Mitsiades, Salma Kaochar, Chong-Xian Pan, Luis G Carvajal-Carmona, Alana L Welm, Bryan E Welm, Ramaswamy Govindan, Shunqiang Li, Michael A Davies, Jack A Roth, Funda Meric-Bernstam, Yang Xie, Meenhard Herlyn, Li Ding, Michael T Lewis, Carol J Bult, Dennis A Dean, Jeffrey H Chuang

Faculty, Staff and Students Publications

Patient-derived xenografts (PDX) model human intra- and intertumoral heterogeneity in the context of the intact tissue of immunocompromised mice. Histologic imaging via hematoxylin and eosin (H&E) staining is routinely performed on PDX samples, which could be harnessed for computational analysis. Prior studies of large clinical H&E image repositories have shown that deep learning analysis can identify intercellular and morphologic signals correlated with disease phenotype and therapeutic response. In this study, we developed an extensive, pan-cancer repository of >1,000 PDX and paired parental tumor H&E images. These images, curated from the PDX Development and Trial Centers Research Network Consortium, had a …

14-3-3Ζ Suppresses Rankl Signaling By Destabilizing Traf6, R. Ayyasamy, S. Fan, P. Czernik, B. Lecka-Czernik, Somsubhra Chattopadhyay, R. Chakravarti

Markey Cancer Center Faculty Publications

Macrophages are essential regulators of inflammation and bone loss. Receptor activator of nuclear factor-κβ ligand (RANKL), a pro-inflammatory cytokine, is responsible for macrophage differentiation to osteoclasts and bone loss. We recently showed that 14-3-3ζ-knockout (Ywhaz^KO) rats exhibit increased bone loss in the inflammatory arthritis model. 14-3-3ζ is a cytosolic adaptor protein that actively participates in many signaling transductions. However, the role of 14-3-3ζ in RANKL signaling or bone remodeling is unknown. We investigated how 14-3-3ζ affects osteoclast activity by evaluating its role in RANKL signaling. We utilized 14-3-3ζ-deficient primary bone marrow–derived macrophages obtained from wildtype and Ywhaz^{KO …}

Microbiomes In Birds: A Review Of Links To Health And Reproduction, Mary Ann Ottinger, Shailaja Mani, Sonja Krüger, Brent Coverdale, Sandi Willows-Munro, Leigh Combrink

Faculty, Staff and Students Publications

Microbiomes have emerged as a key component essential for maintaining the health of an organism. Additionally, the roles of microbiomes are multifaceted, some unique to specific body areas and organs while others, particularly the gut microbiome, having broader effects on the entire organism. Comparative literature is emerging that compares microbiomes across mammals and birds. Domestic poultry have been the most extensively studied relative to their role in production agriculture. These data have provided a great deal of information about the effects of diet and nutritional requirements relative to the gut microbiome, productivity, and resilience to diseases. Conversely, limited research has …

Analyzing Efficiency Of A Lentiviral Shrna Knockdown System In Human Enteroids Using Western Blot And Flow Cytometry, Adam P Wilson, Karni S Moshal, Addison P Franca, Sasirekha Ramani, Randle Gallucci, Hala Chaaban, Kathryn Y Burge

Faculty, Staff and Students Publications

Enteroids are in vitro models to study gastrointestinal pathologies and test personalized therapeutics; however, the inherent complexity of enteroids often renders standard gene editing approaches ineffective. Here, we introduce a refined lentiviral transfection protocol, ensuring sufficient lentiviral engagement with enteroids while considering spatiotemporal growth variability throughout the extracellular matrix. Additionally, we highlight a selection process for transduced cells, introduce a protocol to accurately measure transduction efficiency, and explore methodologies to gauge effects of gene knockdown on biological processes.

Leveraging Integrated Rna Sequencing To Decipher Adrenomedullin's Protective Mechanisms In Experimental Bronchopulmonary Dysplasia, Subarna Palit, Amrit Kumar Shrestha, Shyam Thapa, Sandra L Grimm, Cristian Coarfa, Fabian Theis, Lukas M Simon, Binoy Shivanna

Faculty, Staff and Students Publications

Bronchopulmonary dysplasia (BPD) is a chronic lung disease commonly affecting premature infants, with limited therapeutic options and increased long-term consequences. Adrenomedullin (Adm), a proangiogenic peptide hormone, has been found to protect rodents against experimental BPD. This study aims to elucidate the molecular and cellular mechanisms through which Adm influences BPD pathogenesis using a lipopolysaccharide (LPS)-induced model of experimental BPD in mice. Bulk RNA sequencing of Adm-sufficient (wild-type or Adm+/+) and Adm-haplodeficient (Adm+/−) mice lungs, integrated with single-cell RNA sequencing data, revealed distinct gene expression patterns and cell type alterations associated with Adm deficiency …

Deciphering The Microbial Fingerprint Of Covid-19: A Multi-Layered Exploration Of The Oral And Gut Microbiome Dysbiosis, Iman Mostafa Sultan

Theses and Dissertations

The impact of SARS-CoV-2 infection on the human microbiome remains a dynamic and intricate puzzle. This study delves deeper into this mystery by revisiting the oral and gut microbial compositions of 53 COVID-19 patients before and after viral clearance, alongside comparisons to 76 healthy individuals. Through a comparative lens, we have emploed two distinct differential abundance methods – DeSeq2 and ANCOM – while drawing upon the thorough SILVA database encompassing the full-length 16S rRNA gene. The analysis underscores the crucial role of a diverse methodological choir in microbiome research. In certain instances, the congruence between DeSeq2 and ANCOM may exhibit …

In-Silico Analysis Of Tmem2 As A Pancreatic Adenocarcinoma And Cancer-Associated Fibroblast Biomarker, And Functional Characterization Of Nsc777201, For Targeted Drug Development, Prateeti Srivastava, Vijesh Kumar Yadav, Tzu-Hao Chang, Emily Chia-Yu Su, Bashir Lawal, Alexander Th Wu, Hsu-Shan Huang

Faculty, Staff and Student Publications

Pancreatic adenocarcinoma (PAAD), known as one of the deadliest cancers, is characterized by a complex tumor microenvironment, primarily comprised of cancer-associated fibroblasts (CAFs) in the extracellular matrix. These CAFs significantly alter the matrix by interacting with hyaluronic acid (HA) and the enzyme hyaluronidase, which degrades HA - an essential process for cancer progression and spread. Despite the critical role of this interaction, the specific functions of CAFs and hyaluronidase in PAAD development are not fully understood. Our study investigates this interaction and assesses NSC777201, a new anti-cancer compound targeting hyaluronidase. This research utilized computational methods to analyze gene expression data …

Identification And Characterization Of Cannabichromene's Major Metabolite Following Incubation With Human Liver Microsomes, Alexandra M Ward, Touraj Shokati, Jost Klawitter, Jelena Klawitter, Vu Nguyen, Laura Kozell, Atheir I Abbas, David Jones, Uwe Christians

Faculty, Staff and Student Publications

Cannabichromene (CBC) is a minor cannabinoid within the array of over 120 cannabinoids identified in the Cannabis sativa plant. While CBC does not comprise a significant portion of whole plant material, it is available to the public in a purified and highly concentrated form. As minor cannabinoids become more popular due to their potential therapeutic properties, it becomes crucial to elucidate their metabolism in humans. Therefore, the goal of this was study to identify the major CBC phase I-oxidized metabolite generated in vitro following incubation with human liver microsomes. The novel metabolite structure was identified as 2′-hydroxycannabicitran using gas chromatography–mass …

Mycoplasmoides Genitalium Nucleic Acid Semi-Quantitation And Molecular Macrolide Resistance Detection Via Automated Assays: Gender And Specimen Source Considerations, Erik Munson, Josephine Moore, Trinity Krueger, Amanda Zapp, Stephen C Lavey, Kimber L Munson, Irene A Stafford, Brian Mustanski

Faculty, Staff and Student Publications

A laboratory-developed test (LDT) using analyte-specific reagents has been optimized on a commercial platform to detect macrolide resistance-associated mutations (MRM) in 23S rRNA from Mycoplasmoides genitalium from primary clinical specimens. In this study, MRM-LDT was applied to a multi-specimen source study set. One thousand four hundred ninety-five primary specimens testing positive for M. genitalium by commercial transcription-mediated amplification (TMA) were initially titered by the TMA assay using serial 10-fold dilutions to semi-quantitate target nucleic acid burden. Primary specimens were then processed for MRM detection using the MRM-LDT. Findings were stratified by gender and specimen source. The mean log10 target nucleic …

Quantitative Proteomic Analysis Reveals Unique Hsp90 Cycle-Dependent Client Interactions, Erick I Rios, Davi Gonçalves, Kevin A Morano, Jill L Johnson

Faculty, Staff and Student Publications

Hsp90 is an abundant and essential molecular chaperone that mediates the folding and activation of client proteins in a nucleotide-dependent cycle. Hsp90 inhibition directly or indirectly impacts the function of 10-15% of all proteins due to degradation of client proteins or indirect downstream effects. Due to its role in chaperoning oncogenic proteins, Hsp90 is an important drug target. However, compounds that occupy the ATP-binding pocket and broadly inhibit function have not achieved widespread use due to negative effects. More selective inhibitors are needed; however, it is unclear how to achieve selective inhibition. We conducted a quantitative proteomic analysis of soluble …

Medmicromaps, A Novel Decision-Tree Guide For Infectious Diseases Differential Diagnoses, And Evaluation Of Pre- And Post-Pandemic User Engagement By Preclinical Medical Students, Jason Ceballos, Tavsimran Luthra, Lucia Garces-Torres, Valerie Lentz, Jack Nelson, Claudia Carceles-Roman, Ian Holyoak, Jane Harrington

International Journal of Emerging and Disruptive Innovation in Education : VISIONARIUM

Background: Medical education has undergone major changes in the past 5 years to adapt to the digital-centered student population with diverse learning preferences. To address the challenges of shifting delivery modalities, multimedia resources were created to provide interactive e-learning material on infectious diseases for year 2 medical students.

Methods: Medical students at a USA-accredited Caribbean medical school were provided with supplemental e-learning materials including animations, illustrations, diagnostic algorithms aka MedMicroMaps, and Case-Based tutorials. Participants were classified by semester and lecture delivery: In-person: Cohort 1 (n=526); Virtual: Cohort 2 (n=651); and Hybrid: Cohort 3 ( …

Cyp3a Mediates An Unusual C(Sp2)-C(Sp3) Bond Cleavage Via Ipso-Addition Of Oxygen In Drug Metabolism, Xuan Qin, Yong Wang, Qiuji Ye, John M Hakenjos, Jin Wang, Mingxing Teng, Lei Guo, Zhi Tan, Damian W Young, Kevin R Mackenzie, Feng Li

Faculty, Staff and Students Publications

Mammalian cytochrome P450 drug-metabolizing enzymes rarely cleave carbon–carbon (C-C) bonds and the mechanisms of such cleavages are largely unknown. We identified two unusual cleavages of non-polar, unstrained C(sp2)-C(sp3) bonds in the FDA-approved tyrosine kinase inhibitor pexidartinib that are mediated by CYP3A4/5, the major human phase I drug metabolizing enzymes. Using a synthetic ketone, we rule out the Baeyer-Villiger oxidation mechanism that is commonly invoked to address P450-mediated C-C bond cleavages. Our studies in 18O2 and H218O enriched systems reveal two unusual distinct mechanisms of C-C bond cleavage: one bond is cleaved by CYP3A-mediated ipso-addition of oxygen to a C(sp2) …

Clonality And Epidemiological Studies Of E. Coli Strain Collected From Abu Dhabi Emirate Using Ngs And Bioinformatic Tools, Ahmed Abdelrahman Mohamed

Theses

In the current landscape, where antibiotic resistance in bacteria is steadily rising, the role of bacterial genomics has assumed increasing significance. Therefore, it is necessary for microbiologists to acquire proficiency in the utilization of these methods and tools to harness their potential in gaining valuable insights into bacterial genomes. This can facilitate the development of innovative strategies for managing and treating bacterial infections. Here we present the power of the whole-genome sequencing technology in characterization of multidrug resistant Escherichia coli isolates. Fourteen Escherichia coli isolates were selected for this study. Following the standard microbiological techniques to confirm the sample identification, …

Multidisciplinary Training In Dermatology: Exploring The Spectrum Of Board Certifications Among Physicians Practicing Dermatology In Texas, Rebecca H Lee, Jason Lee, Jonny Hatch, Lilian Zhan, Braden Van Alfen, Mark Conley, Tracy Zhao, Carlos Gomez-Meade

Faculty, Staff and Students Publications

Dermatology, a medical specialty focused on skin, hair, and nail conditions, often overlaps with various medical specialties. Although most physicians practicing dermatology are board-certified in dermatology, there are physicians practicing dermatology who are board-certified in a variety of different medical specialties. This cross-sectional study examines the board certifications of physicians who reported practicing dermatology in Texas. Data were sourced from the Texas Medical Board database updated in August 2023. The data showed that out of 1,614 practicing physicians declaring dermatology as a specialty in Texas, 1,080 (66.91%) physicians had one board certification, 200 (12.39%) had two, and 15 (0.93%) had …

The Kat Module Of The Saga Complex Maintains The Oncogenic Gene Expression Program In Mycn- Amplified Neuroblastoma, Clare F Malone, Nathaniel W Mabe, Alexandra B Forman, Gabriela Alexe, Kathleen L Engel, Ying-Jiun C Chen, Melinda Soeung, Silvi Salhotra, Allen Basanthakumar, Bin Liu, Sharon Y R Dent, Kimberly Stegmaier

Faculty, Staff and Student Publications

Pediatric cancers are frequently driven by genomic alterations that result in aberrant transcription factor activity. Here, we used functional genomic screens to identify multiple genes within the transcriptional coactivator Spt-Ada-Gcn5-acetyltransferase (SAGA) complex as selective dependencies for MYCN-amplified neuroblastoma, a disease of dysregulated development driven by an aberrant oncogenic transcriptional program. We characterized the DNA recruitment sites of the SAGA complex in neuroblastoma and the consequences of loss of SAGA complex lysine acetyltransferase (KAT) activity on histone acetylation and gene expression. We demonstrate that loss of SAGA complex KAT activity is associated with reduced MYCN binding on chromatin, suppression of …

Twist1 Drives Cytotoxic Cd8+ T-Cell Exhaustion Through Transcriptional Activation Of Cd274 (Pd-L1) Expression In Breast Cancer Cells, Xiaobin Yu, Jianming Xu

Faculty, Staff and Students Publications

In breast cancer, epithelial-mesenchymal transition (EMT) is positively associated with programmed death ligand 1 (PD-L1) expression and immune escape, and TWIST1 silences ERα expression and induces EMT and cancer metastasis. However, how TWIST1 regulates PD-L1 and immune evasion is unknown. This study analyzed TWIST1 and PD-L1 expression in breast cancers, investigated the mechanism for TWIST1 to regulate PD-L1 transcription, and assessed the effects of TWIST1 and PD-L1 in cancer cells on cytotoxic CD8+ T cells. Interestingly, TWIST1 expression is correlated with high-level PD-L1 expression in ERα-negative breast cancer cells. The overexpression and knockdown of TWIST1 robustly upregulate and downregulate PD-L1 …