Medicine and Health Sciences Commons^™

Purification And Biochemical Characterization Of The Dna Binding Domain Of The Nitrogenase Transcriptional Activator Nifa From Gluconacetobacter Diazotrophicus, Heidi G. Standke, Lois Kim, Cedric P. Owens

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

NifA is a σ⁵⁴ activator that turns on bacterial nitrogen fixation under reducing conditions and when fixed cellular nitrogen levels are low. The redox sensing mechanism in NifA is poorly understood. In α- and β-proteobacteria, redox sensing involves two pairs of Cys residues within and immediately following the protein’s central AAA⁺ domain. In this work, we examine if an additional Cys pair that is part of a C(X)5 C motif and located immediately upstream of the DNA binding domain of NifA from the α-proteobacterium Gluconacetobacter diazotrophicus (Gd) is involved in redox sensing. We hypothesize that the …

Role Of Phosphorylated Dicer1 In Tumor Progression, Raisa Reyes-Castro

Dissertations & Theses (Open Access)

DICER1 is a multidomain enzyme discovered and widely recognized for its function in small non-coding microRNA (miRNA) synthesis. In cancer development, DICER1 functions as a haploinsufficient tumor suppressor which regulates miRNAs and Epithelial-to-Mesenchymal Transition (EMT). The Arur laboratory discovered that DICER1 is phosphorylated by active ERK and that ERK-mediated phosphorylation triggers DICER1 to translocate from the cytoplasm to the nucleus of cells in worms, mice and humans. Further, a heterozygous allele of a genetically engineered mouse model of phosphomimetic Dicer1 when combined with heterozygous Kras oncogenic background contributes to lung tumor progression in vivo. Mechanisms through which phosphomimetic Dicer1 …

Extracellular Trna-Derived Rnas As Emerging Activators Of Endosomal Toll-Like Receptors: A Narrative Review, Justin Gumas, Yohei Kirino

Computational Medicine Center Faculty Papers

Background and Objective: The innate immune system deploys various pattern-recognition receptors (PRRs), including Toll-like receptors (TLRs), to detect the invasion of pathogens and initiate protective responses. TLR7 and TLR8 are located within the endosome of immune cells and are activated by single-stranded RNAs (ssRNAs). In addition to foreign ssRNAs from bacteria and viruses, endogenous self-ssRNAs, such as microRNAs (miRNAs), have been shown to activate TLR7 and TLR8, but such endogenous ssRNA ligands have not yet been fully elucidated. This scientific knowledge gap is partly derived from the technical limitations of standard RNA-seq, particularly its inability to capture non-miRNA-short non-coding RNAs …

Investigating The Role Of Endothelial Breast Cancer Susceptibility Gene 2 In Doxorubicin-Induced Cardiotoxicity, Berk U. Rasheed

Electronic Thesis and Dissertation Repository

Doxorubicin (Dox) is a chemotherapeutic drug used to treat various malignancies including breast and ovarian cancers. Accumulating evidence implicates cardiac impairments associated with Dox treatment. The Breast Cancer Susceptibility Gene 2 (BRCA2) functions to maintain genome-wide stability by promoting DNA-damage repair. Accordingly, cardiomyocyte damage is specifically regulated by contributors of DNA damage repair such as BRCA2. The endothelium, the innermost cells of every blood vessel, act to protect our tissues from noxious elements, however, recent evidence suggests that BRCA2 knockdown compromises endothelial cell function. A putative role of endothelial BRCA2 during Dox-induced cardiotoxicity (DIC) remains unknown. We hypothesized that endothelial-specific …

Incubation With Porcine Urinary Bladder Matrix Yields A Late-Stage Wound Transcriptome In Endothelial Cells And Keratinocytes Isolated From Both Diabetic And Non-Diabetic Subjects, John T. Paige, Daniel J. Lightell, Hunter F. Douglas, Natasha C. Klingenberg, Thaidan Pham, T. Cooper Woods

School of Medicine Faculty Publications

Proper wound closure requires the functional coordination of endothelial cells (ECs) and keratinocytes. In the late stages of wound healing, keratinocytes become activated and ECs promote the maturation of nascent blood vessels. In diabetes mellitus, decreased keratinocyte activation and impaired angiogenic action of ECs delay wound healing. Porcine urinary bladder matrix (UBM) improves the rate of wound healing, but the effect of exposure to UBM under diabetic conditions remains unclear. We hypothesized that keratinocytes and ECs isolated from both diabetic and non-diabetic donors would exhibit a similar transcriptome representative of the later stages of wound healing following incubation with UBM. …

Sars-Cov-2 Next Generation Sequencing (Ngs) Data From Clinical Isolates From The East Texas Region Of The United States, Rob E. Carpenter, Vaibhav K. Tamrakar, Advanta Genetics

Human Resource Development Faculty Publications and Presentations

The SARS-CoV-2 virus has evolved throughout the pandemic and is likely to continue evolving into new variants. Some of these variants may affect functional properties, including infectivity, interactions with host immunity, and disease severity. And compromised vaccine efficacy is an emerging concern with every new viral variant. Next-generation sequencing (NGS) has emerged as the tool of choice for discovering new variants and understanding the transmission dynamics of SARS-CoV-2. Deciphering the SARS-CoV-2 genome has enabled epidemiological survivance and forecast of altered etiologically. Clinical presentations of the infection are influenced by comorbidities such as age, immune status, diabetes, and the infecting variant. …

Orthologs Of The C. Elegans Heterochronic Genes Have Divergent Functions In C. Briggsae, Maria Ivanova, Eric G. Moss

Rowan-Virtua Research Day

The heterochronic genes of C. elegans comprise the best-studied pathway controlling the timing of tissue and organ formation in an animal. To begin to understand the evolution of this pathway, the significance of each factor, and the relationships among the components, we characterized 11 C. briggsae orthologs of C. elegans heterochronic genes. Using CRISPR/Cas9, we made a variety of alleles and found that several mutant phenotypes differ in significant ways from those of C. elegans. Although most orthologs displayed defects in developmental timing, those phenotypes could differ in which stages they controlled, the penetrance and expressivity of the phenotypes, or …

Differential Degeneration Of Neurons In A Mouse Model Of Canavan Disease, Vibha Chauhan, Quy Nguyen, Jeremy Francis, Paola Leone

Rowan-Virtua Research Day

Canavan disease (CD) is an inherited leukodystrophy caused by inactivating mutations to the glial enzyme aspartoacylase (ASPA). ASPA catabolizes neuronal N-acetylaspartate (NAA) into free acetate and aspartate and loss of this function results in the chronic elevation of non-catabolized NAA and the failure of developmental myelination. Elevated NAA is thought to cause damage to myelin and myelin-producing cells (oligodendrocytes, but the viability of neurons in CD is relatively unexplored. We compare here the progressive degeneration of neurons in two regions of the CD mouse brain, the thalamus and the cortex, distinguished by differing degrees of vacuolation, and show that the …

Utilizing Ultra-Performance Chromatography High-Resolution Mass Spectrometry To Investigate Fatty Acid Mediated Antibiotic Tolerance, Brittni Woodall

Doctoral Dissertations

The lipid membrane is the first component necessary to sustain life. To maintain homeostasis, segregate cellular machinery, provide protection from the environment, and reproduce, an organism must establish a boundary in which the processes can occur. Throughout the last two decades, research has propelled our knowledge of lipid membranes much beyond original hypotheses. Once thought of to be static and uniform, the understanding of the lipid membrane has evolved to encompass a structure that is responsive, unique, and intricately constructed by the organism itself. By chance or by choice, organisms adapt the lipid membrane according to the environment for which …

The Presence Of Childhood Obesity In Nebraska And The Physiological Repercussions Of The Disease, Madison R. Bezousek

Honors Theses

Childhood Obesity can cause lifelong repercussions in children and adults. There has been stigma around the causes of obesity and its relation to lifestyle choices, without consideration of the genetic and syndromic causes. In this literature review the causes of obesity were investigated, along with the effect on the physiological systems and the enviornmental factors that are continuing the obesity epidemic. Preventing and treating lifestyle obesity is something that is seen to have the greatest effect on youth, especially with intergenerational obesity. Nebraska schools have implemented programs to encourage healthy living, and ongoing research is being implemented to reduce the …

The Genetic Determinants Of Recurrent Somatic Mutations In 43,693 Blood Genomes, Joshua S. Weinstock, Cecelia A. Laurie, Jai G. Broome, Kent D. Taylor, Xiuqing Guo, Alan R. Shuldiner, Jeffrey R. O'Connell, Ravi Duggirala, Joanne E. Curran, John Blangero

School of Medicine Publications and Presentations

Nononcogenic somatic mutations are thought to be uncommon and inconsequential. To test this, we analyzed 43,693 National Heart, Lung and Blood Institute Trans-Omics for Precision Medicine blood whole genomes from 37 cohorts and identified 7131 non-missense somatic mutations that are recurrently mutated in at least 50 individuals. These recurrent non-missense somatic mutations (RNMSMs) are not clearly explained by other clonal phenomena such as clonal hematopoiesis. RNMSM prevalence increased with age, with an average 50-year-old having 27 RNMSMs. Inherited germline variation associated with RNMSM acquisition. These variants were found in genes involved in adaptive immune function, proinflammatory cytokine production, and lymphoid …

Meta-Narrative Review Of Possible Impacts Of Genetic Screening On Treatment Of Breast Cancer, Toqa Al Alawi, Sheza Khan, Ivey Knebel, Steven Luong, Vilma Sanchez, Kamilah Walker-Charles

Research Methods Poster Session 2023

Objective: To examine the impacts of genetic screening on the treatment of breast cancer, in relation to differences, outcomes and decisions in treatment plans or surgery in patients that performed genetic screening versus those that did not.

Background: Genetic screening technology has become commercially available, yet standard preventative care for breast cancer has no genetic screening involved. Genetic screening in breast cancer treatment is performed, but its usage is not standardized.

Methods: Findings were synthesized using the meta-narrative review style to examine articles retrieved from searches of digital databases PubMed and the M.D. Anderson Scholarly Library.

Discussion: Articles were selected …

Anterior And Posterior Tongue Regions And Taste Papillae: Distinct Roles And Regulatory Mechanisms With An Emphasis On Hedgehog Signaling And Antagonism., Archana Kumari, Charlotte M. Mistretta

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Sensory receptors across the entire tongue are engaged during eating. However, the tongue has distinctive regions with taste (fungiform and circumvallate) and non-taste (filiform) organs that are composed of specialized epithelia, connective tissues, and innervation. The tissue regions and papillae are adapted in form and function for taste and somatosensation associated with eating. It follows that homeostasis and regeneration of distinctive papillae and taste buds with particular functional roles require tailored molecular pathways. Nonetheless, in the chemosensory field, generalizations are often made between mechanisms that regulate anterior tongue fungiform and posterior circumvallate taste papillae, without a clear distinction that highlights …

Parp1 Associates With R-Loops To Promote Their Resolution And Genome Stability, Natalie Laspata, Parminder Kaur, Sofiane Yacine Mersaoui, Daniela Muoio, Zhiyan Silvia Liu, Maxwell Henry Bannister, Hai Dang Nguyen, Caroline Curry, John M. Pascal, Guy G. Poirier, Hong Wang, Jean-Yves Masson, Elise Fouquerel

Student Papers, Posters & Projects

PARP1 is a DNA-dependent ADP-Ribose transferase with ADP-ribosylation activity that is triggered by DNA breaks and non-B DNA structures to mediate their resolution. PARP1 was also recently identified as a component of the R-loop-associated protein-protein interaction network, suggesting a potential role for PARP1 in resolving this structure. R-loops are three-stranded nucleic acid structures that consist of a RNA-DNA hybrid and a displaced non-template DNA strand. R-loops are involved in crucial physiological processes but can also be a source of genome instability if persistently unresolved. In this study, we demonstrate that PARP1 binds R-loops in vitro and associates with R-loop formation …

Sperm Dna Integrity In Absolute Teratozoospermia Patients And Its Impact On Assisted Reproductive Technology Outcome, Dina Faris

Theses and Dissertations

Sperm DNA Fragmentation (SDF) is a common cause of male infertility, although it is underdiagnosed due to lack of routine testing. High levels of SDF are reported in men with abnormal sperm morphology. However, the implications of such findings on live birth following Intracytoplasmic Sperm Injection (ICSI) have not been studied in absolute teratozoospermia men (100% abnormal sperm morphology). In this prospective study, the severity of DNA damage was evaluated in absolute teratozoospermia patients and its impact on ICSI outcomes, particularly live birth rate. My study included 36 men with absolute teratozoospermia and 30 men with normal sperm. Real-time assessment …

Evaluation Of Genetic Alterations In Hereditary Cancer Susceptibility Genes In The Ashkenazi Jewish Women Community Of Mexico, Clara Estela Díaz-Velásquez, Rina Gitler, Adriana Antoniano, Ronny Kershenovich Sefchovich, Aldo Hugo De La Cruz-Montoya, Héctor Martínez-Gregorio, Ernesto Arturo Rojas-Jiménez, Ricardo Cortez Cardoso Penha, Luis Ignacio Terrazas, Talia Wegman-Ostrosky, Ephrat Levi-Lahad, Jovanny Zabaleta, Sandra Perdomo, Felipe Vaca-Paniagua

School of Medicine Faculty Publications

Background: Individuals of Ashkenazi Jewish ancestry have been identified as having higher prevalence of specific pathogenic variants associated with susceptibility to specific rare and chronic diseases. In Mexico, the prevalence and composition of rare cancer predisposing germline variants in Ashkenazi Jewish individuals has not been evaluated. Aim and methods: We aimed to evaluate the prevalence of pathogenic variants by massive parallel sequencing in a panel of 143 cancer-predisposing genes in 341 women from the Ashkenazi Jewish community of Mexico, who were contacted and invited to participate in the study through the ALMA Foundation for Cancer Reconstruction. Pre- and posttest genetic …

Immunotherapeutic Targets In Non-Small Cell Lung Cancer, Habib Sadeghirad, Tayyeb Bahrami, Sepideh M. Layeghi, Hassan Yousefi, Meysam Rezaei, Seyed R. Hosseini-Fard, Payar Radfar, Majid E. Warkiani, Ken O'Byrne, Arutha Kulasinghe

School of Medicine Faculty Publications

Non-small cell lung cancer (NSCLC) is one of the most common types of cancer in the world and has a 5-year survival rate of ~20%. Immunotherapies have shown promising results leading to durable responses, however, they are only effective for a subset of patients. To determine the best therapeutic approach, a thorough and in-depth profiling of the tumour microenvironment (TME) is required. The TME is a complex network of cell types that form an interconnected network, promoting tumour cell initiation, growth and dissemination. The stroma, immune cells and endothelial cells that comprise the TME generate a plethora of cytotoxic or …

Histoplasma Tympanomastoiditis: Case Report And Literature Review, Terrence Park, Gordon Love, Victoria Burke

School of Medicine Faculty Publications

Histoplasma is a dimorphic fungus capable of producing a diverse array of clinical pathology in humans dependent upon the host immune status. Acute symptomatic infection typically presents as an isolated pulmonary or nodal disease in immunocompetent patients with extra-thoracic manifestations rarely seen in this population. In this report, we describe a novel case of Histoplasma capsulatum tympanomastoiditis in an immunocompetent patient who presented with progressively worsening purulent otorrhea, vertigo, and facial nerve palsy. He was successfully managed with surgical debridement and a prolonged antifungal course.

Investigation Of The Dyrk1a Regulation By Lzts2-Sipa1l1 Complex, Rebecca Gunnin, Austin Witt B.S., Larisa Litovchick M.D.,Ph.D.

Undergraduate Research Posters

A region on chromosome 21, the Down Syndrome critical region (DSCR), is associated with major defects found in Down Syndrome, such as craniofacial malformations. DYRK1A is a gene found on chromosome 21 within the DSCR that encodes an enzyme, dual specificity tyrosine-phosphorylation-regulated kinase 1A. DYRK1A is known to phosphorylate many substrate proteins and is thought to be involved in tumor suppression, neurological development, cell cycle regulation, and aging. Recently, the Litovchick lab and others reported that DYRK1A also plays a role in the double-strand break repair of DNA, which could lead to mutations and tumorigenesis, if deregulated.

The Litovchick lab …

Effects That The Methylenetetrahydrofolate Gene Mutation (Both The C677t And A1298c Polymorphisms) Have On Both Men And Women’S Fertility Abilities And Subsequent Fetal Development, As Well As What Nutritional Changes Can Possibly Do To Aid In Reversing These Supposed Negative Effects., Elizabeth Simkanin

Williams Honors College, Honors Research Projects

This study discusses the perceived negative effects of variants (C677T and A1298C) of the methylenetetrahydrofolate (MTHFR) gene on male and female fertility and fetal development, as well as the potential for nutrition changes to aid in reversing these negative effects. This research project was completed in order to discuss the possible association with and connection between nutrition and fertility in both male and female individuals who have either of the two most common MTHFR gene polymorphisms, 677C>T and 1298A>C. These two polymorphisms are of particular interest because they are associated with the most decreased activity of the MTHFR …