Biological Phenomena, Cell Phenomena, and Immunity Commons^™

A Novel Sequential Compression Appliance To Reduce Scarring Of The Face, Michelle N. Dwertman, Henry B. Huson

School of Medicine Faculty Publications

56th Annual Meeting of the American Burn Association, ABA 2024; April 9 - 12, 2024, Chicago, IL

Emerging Variants Develop Total Escape From Potent Monoclonal Antibodies Induced By Ba4/5 Infection, Chang Liu, Raksha Das, Aiste Dijokaite-Guraliuc, Daming Zhou, Alexander J Mentzer, Piyada Supasa, Muneeswaran Selvaraj, Helen M E Duyvesteyn, Thomas G Ritter, Nigel Temperton, Paul Klenerman, Susanna J Dunachie, Neil G Paterson, Mark A Williams, David R Hall, Elizabeth E Fry, Juthathip Mongkolsapaya, Jingshan Ren, David I Stuart, Gavin R Screaton

Faculty, Staff and Student Publications

The rapid evolution of SARS-CoV-2 is driven in part by a need to evade the antibody response in the face of high levels of immunity. Here, we isolate spike (S) binding monoclonal antibodies (mAbs) from vaccinees who suffered vaccine break-through infections with Omicron sub lineages BA.4 or BA.5. Twenty eight potent antibodies are isolated and characterised functionally, and in some cases structurally. Since the emergence of BA.4/5, SARS-CoV-2 has continued to accrue mutations in the S protein, to understand this we characterize neutralization of a large panel of variants and demonstrate a steady attrition of neutralization by the panel of …

Jennifer A Wargo, Nadim J Ajami, And Carrie R Daniel-Macdougall, Jennifer A Wargo, Nadim J Ajami, Carrie R Daniel-Macdougall

Faculty, Staff and Student Publications

Dr. Jennifer A. Wargo, Dr. Nadim J. Ajami, and Dr. Carrie R. Daniel-MacDougall describe their academic and clinical work on the role of the microbiome to determine response to immunotherapies and discuss current challenges and potential needs to integrate their findings into clinical practice.

Multilocus Pathogenic Variants Contribute To Intrafamilial Clinical Heterogeneity: A Retrospective Study Of Sibling Pairs With Neurodevelopmental Disorders, Tugce Bozkurt-Yozgatli, Davut Pehlivan, Richard A Gibbs, Ugur Sezerman, Jennifer E Posey, James R Lupski, Zeynep Coban-Akdemir

Faculty, Staff and Students Publications

BACKGROUND: Multilocus pathogenic variants (MPVs) are genetic changes that affect multiple gene loci or regions of the genome, collectively leading to multiple molecular diagnoses. MPVs may also contribute to intrafamilial phenotypic variability between affected individuals within a nuclear family. In this study, we aim to gain further insights into the influence of MPVs on a disease manifestation in individual research subjects and explore the complexities of the human genome within a familial context.

METHODS: We conducted a systematic reanalysis of exome sequencing data and runs of homozygosity (ROH) regions of 47 sibling pairs previously diagnosed with various neurodevelopmental disorders (NDD). …

An Exploration Of The Effectiveness Of Xanthorrhiza Simplicissima And Its Secondary Alkaloids As Antibiotics Against Staphylococcus Aureus With The Use Of Reserpine, Donald Bothe, Savita Chaurasia

Undergraduate Theses

Xanthorhiza simplicissima is a plant that is steeped in medical history. It has been used for hundreds of years by the Native Americans, and later by the Europeans, of Appalachia for its medicinal properties. One of the most useful medical applications of this plant are its antibiotic properties, as typified by its use as a tea that was consumed to treat mouth sores. These antibiotic properties can be attributed to some of its secondary alkaloids such as berberine, liriodenine, oxyacanthine, and magnoflorine. These compounds have been studied in other systems; however, oxyacanthine and magnoflorine have not been researched in tandem …

Water, Sanitation, And Hygiene Infrastructure And Resources In Schools In Belize During The Covid-19 Pandemic, 2021-2023, Anh N Ly, Kelsey Mcdavid, Christina Craig, Dian Maheia, Yolanda Gongora, Alexandra Medley, Francis Morey, Russell Manzanero, Gerhaldine Morazan, Allison Lino, Vickie Romero, Rosalva Blanco, Kanako Ishida, Matthew Lozier, Kristy O Murray

Faculty, Staff and Students Publications

Access to water, sanitation, and hygiene (WASH) resources in schools is critical for disease prevention and control, especially during public health emergencies. In Belize, systematic, national data on WASH in schools are needed to inform public health decisions and interventions. From December 2021 to January 2022, a national survey was sent electronically to government and government-aided primary and secondary schools in Belize (N = 308) to gather information on WASH services. From the survey, 12 pilot schools were selected based on the highest self-reported need for WASH resources to participate in additional evaluation and intervention, which included environmental nudges, supplemental …

Charting The Cellular Biogeography In Colitis Reveals Fibroblast Trajectories And Coordinated Spatial Remodeling, Paolo Cadinu, Kisha N Sivanathan, Aditya Misra, Rosalind J Xu, Davide Mangani, Evan Yang, Joseph M Rone, Katherine Tooley, Yoon-Chul Kye, Lloyd Bod, Ludwig Geistlinger, Tyrone Lee, Randall T Mertens, Noriaki Ono, Gang Wang, Liliana Sanmarco, Francisco J Quintana, Ana C Anderson, Vijay K Kuchroo, Jeffrey R Moffitt, Roni Nowarski

Faculty, Staff and Student Publications

Gut inflammation involves contributions from immune and non-immune cells, whose interactions are shaped by the spatial organization of the healthy gut and its remodeling during inflammation. The crosstalk between fibroblasts and immune cells is an important axis in this process, but our understanding has been challenged by incomplete cell-type definition and biogeography. To address this challenge, we used multiplexed error-robust fluorescence in situ hybridization (MERFISH) to profile the expression of 940 genes in 1.35 million cells imaged across the onset and recovery from a mouse colitis model. We identified diverse cell populations, charted their spatial organization, and revealed their polarization …

Targeted Deletion Of Nr2f2 And Vcam1 In Theca Cells Impacts Ovarian Follicular Development: Insights Into Polycystic Ovary Syndrome?†, Nicholes R Candelaria, Joanne S Richards

Faculty, Staff and Students Publications

Defining features of polycystic ovary syndrome (PCOS) include elevated expression of steroidogenic genes, theca cell androgen biosynthesis, and peripheral levels of androgens. In previous studies, we identified vascular cell adhesion molecule 1 (VCAM1) as a selective androgen target gene in specific NR2F2/SF1 (+/+) theca cells. By deleting NR2F2 and VCAM1 selectively in CYP17A1 theca cells in mice, we documented that NR2F2 and VCAM1 impact distinct and sometimes opposing theca cell functions that alter ovarian follicular development in vivo: including major changes in ovarian morphology, steroidogenesis, gene expression profiles, immunolocalization images (NR5A1, CYP11A1, NOTCH1, CYP17A1, INSL3, VCAM1, NR2F2) as well as …

Cd24 Negativity Reprograms Mitochondrial Metabolism To Pparα And Nf-Κb-Driven Fatty Acid Β-Oxidation In Triple-Negative Breast Cancer, Divya Murthy, Debasmita Dutta, Kuldeep S Attri, Tagari Samanta, Sukjin Yang, Kwang Hwa Jung, Sarah G Latario, Vasanta Putluri, Shixia Huang, Nagireddy Putluri, Jun Hyoung Park, Benny Abraham Kaipparettu

Faculty, Staff and Students Publications

CD24 is a well-characterized breast cancer (BC) stem cell (BCSC) marker. Primary breast tumor cells having CD24-negativity together with CD44-positivity is known to maintain high metastatic potential. However, the functional role of CD24 gene in triple-negative BC (TNBC), an aggressive subtype of BC, is not well understood. While the significance of CD24 in regulating immune pathways is well recognized in previous studies, the significance of CD24 low expression in onco-signaling and metabolic rewiring is largely unknown. Using CD24 knock-down and over-expression TNBC models, our in vitro and in vivo analysis suggest that CD24 is a tumor suppressor in metastatic TNBC. …

Wnk Kinase Is A Vasoactive Chloride Sensor In Endothelial Cells, Tessa A C Garrud, Briar Bell, Alejandro Mata-Daboin, Dieniffer Peixoto-Neves, Daniel M Collier, Julio F Cordero-Morales, Jonathan H Jaggar

Faculty, Staff and Student Publications

Endothelial cells (ECs) line the wall of blood vessels and regulate arterial contractility to tune regional organ blood flow and systemic pressure. Chloride (Cl-) is the most abundant anion in ECs and the Cl- sensitive With-No-Lysine (WNK) kinase is expressed in this cell type. Whether intracellular Cl- signaling and WNK kinase regulate EC function to alter arterial contractility is unclear. Here, we tested the hypothesis that intracellular Cl- signaling in ECs regulates arterial contractility and examined the signaling mechanisms involved, including the participation of WNK kinase. Our data obtained using two-photon microscopy and cell-specific inducible knockout mice indicated that acetylcholine, …

Deepdof-Se: Affordable Deep-Learning Microscopy Platform For Slide-Free Histology, Lingbo Jin, Yubo Tang, Jackson B Coole, Melody T Tan, Xuan Zhao, Hawraa Badaoui, Jacob T Robinson, Michelle D Williams, Nadarajah Vigneswaran, Ann M Gillenwater, Rebecca R Richards-Kortum, Ashok Veeraraghavan

Faculty, Staff and Student Publications

Histopathology plays a critical role in the diagnosis and surgical management of cancer. However, access to histopathology services, especially frozen section pathology during surgery, is limited in resource-constrained settings because preparing slides from resected tissue is time-consuming, labor-intensive, and requires expensive infrastructure. Here, we report a deep-learning-enabled microscope, named DeepDOF-SE, to rapidly scan intact tissue at cellular resolution without the need for physical sectioning. Three key features jointly make DeepDOF-SE practical. First, tissue specimens are stained directly with inexpensive vital fluorescent dyes and optically sectioned with ultra-violet excitation that localizes fluorescent emission to a thin surface layer. Second, a deep-learning …

The Saga Of E Faecium, Rishika Prasad, Robert R Jenq

Faculty, Staff and Student Publications

An enzyme that remodels the cell wall of Enterococcus faecium helps these gut bacteria to divide and generate peptide fragments that enhance the immune response against cancer.

Human Brain Glycoform Coregulation Network And Glycan Modification Alterations In Alzheimer's Disease, Qi Zhang, Cheng Ma, Lih-Shen Chin, Sheng Pan, Lian Li

Faculty, Staff and Student Publications

Despite the importance of protein glycosylation to brain health, current knowledge of glycosylated proteoforms or glycoforms in human brain and their alterations in Alzheimer's disease (AD) is limited. Here, we report a proteome-wide glycoform profiling study of human AD and control brains using intact glycopeptide-based quantitative glycoproteomics coupled with systems biology. Our study identified more than 10,000 human brain N-glycoforms from nearly 1200 glycoproteins and uncovered disease signatures of altered glycoforms and glycan modifications, including reduced sialylation and N-glycan branching and elongation as well as elevated mannosylation and N-glycan truncation in AD. Network analyses revealed a higher-order organization of brain …

Bi-Allelic Acbd6 Variants Lead To A Neurodevelopmental Syndrome With Progressive And Complex Movement Disorders, Rauan Kaiyrzhanov, Aboulfazl Rad, Sheng-Jia Lin, Aida Bertoli-Avella, Wouter W Kallemeijn, Annie Godwin, Maha S Zaki, Kevin Huang, Tracy Lau, Cassidy Petree, Stephanie Efthymiou, Ehsan Ghayoor Karimiani, Maja Hempel, Elizabeth A Normand, Sabine Rudnik-Schöneborn, Ulrich A Schatz, Marc P Baggelaar, Muhammad Ilyas, Tipu Sultan, Javeria Raza Alvi, Manizha Ganieva, Ben Fowler, Ruxandra Aanicai, Gulsen Akay Tayfun, Abdulaziz Al Saman, Abdulrahman Alswaid, Nafise Amiri, Nilufar Asilova, Vorasuk Shotelersuk, Patra Yeetong, Matloob Azam, Meisam Babaei, Gholamreza Bahrami Monajemi, Pouria Mohammadi, Saeed Samie, Selina Husna Banu, Jorge Pinto Basto, Fanny Kortüm, Mislen Bauer, Peter Bauer, Christian Beetz, Masoud Garshasbi, Awatif Hameed Issa, Wafaa Eyaid, Hind Ahmed, Narges Hashemi, Kazem Hassanpour, Isabella Herman, Sherozjon Ibrohimov, Ban A Abdul-Majeed, Maria Imdad, Maksudjon Isrofilov, Qassem Kaiyal, Suliman Khan, Brian Kirmse, Janet Koster, Charles Marques Lourenço, Tadahiro Mitani, Oana Moldovan, David Murphy, Maryam Najafi, Davut Pehlivan, Maria Eugenia Rocha, Vincenzo Salpietro, Miriam Schmidts, Adel Shalata, Mohammad Mahroum, Jawabreh Kassem Talbeya, Robert W Taylor, Dayana Vazquez, Annalisa Vetro, Hans R Waterham, Mashaya Zaman, Tina A Schrader, Wendy K Chung, Renzo Guerrini, James R Lupski, Joseph Gleeson, Mohnish Suri, Yalda Jamshidi, Kailash P Bhatia, Barbara Vona, Michael Schrader, Mariasavina Severino, Matthew Guille, Edward W Tate, Gaurav K Varshney, Henry Houlden, Reza Maroofian

Faculty, Staff and Students Publications

The acyl-CoA-binding domain-containing protein 6 (ACBD6) is ubiquitously expressed, plays a role in the acylation of lipids and proteins and regulates the N-myristoylation of proteins via N-myristoyltransferase enzymes (NMTs). However, its precise function in cells is still unclear, as is the consequence of ACBD6 defects on human pathophysiology. Using exome sequencing and extensive international data sharing efforts, we identified 45 affected individuals from 28 unrelated families (consanguinity 93%) with bi-allelic pathogenic, predominantly loss-of-function (18/20) variants in ACBD6. We generated zebrafish and Xenopus tropicalis acbd6 knockouts by CRISPR/Cas9 and characterized the role of ACBD6 on protein N-myristoylation with myristic acid alkyne …

De Novo Variants In Fryl Are Associated With Developmental Delay, Intellectual Disability, And Dysmorphic Features, Xueyang Pan, Alice M Tao, Shenzhao Lu, Mengqi Ma, Shabab B Hannan, Rachel Slaugh, Sarah Drewes Williams, Lauren O'Grady, Oguz Kanca, Richard Person, Melissa T Carter, Konrad Platzer, Franziska Schnabel, Rami Abou Jamra, Amy E Roberts, Jane W Newburger, Anya Revah-Politi, Jorge L Granadillo, Alexander P A Stegmann, Margje Sinnema, Andrea Accogli, Vincenzo Salpietro, Valeria Capra, Lina Ghaloul-Gonzalez, Martina Brueckner, Marleen E H Simon, David A Sweetser, Kevin E Glinton, Susan E Kirk, Baylor College Of Medicine Center For Precision Medicine Models, Michael F Wangler, Shinya Yamamoto, Wendy K Chung, Hugo J Bellen

Faculty, Staff and Students Publications

FRY-like transcription coactivator (FRYL) belongs to a Furry protein family that is evolutionarily conserved from yeast to humans. The functions of FRYL in mammals are largely unknown, and variants in FRYL have not previously been associated with a Mendelian disease. Here, we report fourteen individuals with heterozygous variants in FRYL who present with developmental delay, intellectual disability, dysmorphic features, and other congenital anomalies in multiple systems. The variants are confirmed de novo in all individuals except one. Human genetic data suggest that FRYL is intolerant to loss of function (LoF). We find that the fly FRYL ortholog, furry (fry), is …

The Bone Marrow Endothelial Progenitor Cell Response To Septic Infection, Xin Shi, Kevin J. Simms, Thomas J. Ewing, Yuan-Ping Lin, Yi-Ling Chen, John N. Melvan, Robert W. Siggins, Ping Zhang

School of Graduate Studies Faculty Publications

Early increase in the level of endothelial progenitor cells (EPCs) in the systemic circulation occurs in patients with septic infection/sepsis. The significance and underlying mechanisms of this response remain unclear. This study investigated the bone marrow EPC response in adult mice with septic infection induced by intravenous injection (i.v.) of . For experiments, sorted marrow stem/progenitor cells (SPCs) including lineage(lin)stem cell factor receptor (c-kit)stem cell antigen-1 (Sca-1), linc-kit, and lin cells were cultured with or without lipopolysaccharides (LPSs) and recombinant murine vascular endothelial growth factor (VEGF) in the absence and presence of anti-Sca-1 crosslinking antibodies. In a separate set of …

Swine Influenza A Virus: Challenges And Novel Vaccine Strategies, Erika M. Petro-Turnquist, Matthew J. Pekarek, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Swine Influenza A Virus (IAV-S) imposes a significant impact on the pork industry and has been deemed a significant threat to global public health due to its zoonotic potential. The most effective method of preventing IAV-S is vaccination. While there are tremendous efforts to control and prevent IAV-S in vulnerable swine populations, there are considerable challenges in developing a broadly protective vaccine against IAV-S. These challenges include the consistent diversification of IAV-S, increasing the strength and breadth of adaptive immune responses elicited by vaccination, interfering maternal antibody responses, and the induction of vaccine-associated enhanced respiratory disease after vaccination. Current vaccination …

Gabaergic/Glycinergic And Glutamatergic Neurons Mediate Distinct Neurodevelopmental Phenotypes Of Stxbp1 Encephalopathy, Joo Hyun Kim, Wu Chen, Eugene S Chao, Armando Rivera, Heet Naresh Kaku, Kevin Jiang, Dongwon Lee, Hongmei Chen, Jaimie M Vega, Teresa V Chin, Kevin Jin, Kelly T Nguyen, Sheldon S Zou, Zain Moin, Shawn Nguyen, Mingshan Xue 薛名杉

Faculty, Staff and Students Publications

An increasing number of pathogenic variants in presynaptic proteins involved in the synaptic vesicle cycle are being discovered in neurodevelopmental disorders. The clinical features of these synaptic vesicle cycle disorders are diverse, but the most prevalent phenotypes include intellectual disability, epilepsy, movement disorders, cerebral visual impairment, and psychiatric symptoms ( Verhage and Sørensen, 2020; Bonnycastle et al., 2021; John et al., 2021; Melland et al., 2021). Among this growing list of synaptic vesicle cycle disorders, the most frequent is STXBP1 encephalopathy caused by de novo heterozygous pathogenic variants in syntaxin-binding protein 1 (STXBP1, also known as …

Unveiling Gene Interactions In Alzheimer's Disease By Integrating Genetic And Epigenetic Data With A Network-Based Approach, Keith L Sanders, Astrid M Manuel, Andi Liu, Boyan Leng, Xiangning Chen, Zhongming Zhao

Faculty, Staff and Student Publications

Alzheimer’s Disease (AD) is a complex disease and the leading cause of dementia in older people. We aimed to uncover aspects of AD’s pathogenesis that may contribute to drug repurposing efforts by integrating DNA methylation and genetic data. Implementing the network-based tool, a dense module search of genome-wide association studies (dmGWAS), we integrated a large-scale GWAS dataset with DNA methylation data to identify gene network modules associated with AD. Our analysis yielded 286 significant gene network modules. Notably, the foremost module included the BIN1 gene, showing the largest GWAS signal, and the GNAS gene, the most significantly hypermethylated. We conducted …

Identification Of Novel F2-Isoprostane Metabolites By Specific Udp-Glucuronosyltransferases, Ginger L Milne, Marina S Nogueira, Benlian Gao, Stephanie C Sanchez, Warda Amin, Sarah Thomas, Camille Oger, Jean-Marie Galano, Harvey J Murff, Gong Yang, Thierry Durand

Faculty, Staff and Student Publications

UDP-glucuronosyltransferases (UGTs) catalyze the conjugation of glucuronic acid with endogenous and exogenous lipophilic small molecules to facilitate their inactivation and excretion from the body. This represents approximately 35 % of all phase II metabolic transformations. Fatty acids and their oxidized eicosanoid derivatives can be metabolized by UGTs. F2-isoprostanes (F2-IsoPs) are eicosanoids formed from the free radical oxidation of arachidonic acid. These molecules are potent vasoconstrictors and are widely used as biomarkers of endogenous oxidative damage. An increasing body of evidence demonstrates the efficacy of measuring the β-oxidation metabolites of F2-IsoPs rather than the unmetabolized F2-IsoPs to quantify oxidative damage in …