Medicine and Health Sciences Commons^™

Iron-Dependent Gene Expression In Actinomyces Oris, Matthew P. Mulé, David Giacalone, Kayla Lawlor, Alexa Golden, Caroline Cook, Thomas Lott, Elizabeth Aksten, George A. O'Toole, Lori J. Bergeron

Dartmouth Scholarship

Actinomyces oris is a Gram-positive bacterium that has been associated with healthy and diseased sites in the human oral cavity. Most pathogenic bacteria require iron to survive, and in order to acquire iron in the relatively iron-scarce oral cavity A. oris has been shown to produce iron-binding molecules known as siderophores. The genes encoding these siderophores and transporters are thought to be regulated by the amount of iron in the growth medium and by the metal-dependent repressor, AmdR, which we showed previously binds to the promoter of proposed iron-regulated genes.

The Conserved G-Protein Coupled Receptor Fshr-1 Regulates Protective Host Responses To Infection And Oxidative Stress, Elizabeth V. Miller, Leah N. Grandi, Jennifer A. Giannini, Joseph D. Robinson, Jennifer R. Powell

Biology Faculty Publications

The innate immune system’s ability to sense an infection is critical so that it can rapidly respond if pathogenic microorganisms threaten the host, but otherwise maintain a quiescent baseline state to avoid causing damage to the host or to commensal microorganisms. One important mechanism for discriminating between pathogenic and non-pathogenic bacteria is the recognition of cellular damage caused by a pathogen during the course of infection. InCaenorhabditis elegans, the conserved G-protein coupled receptor FSHR-1 is an important constituent of the innate immune response. FSHR-1 activates the expression of antimicrobial infection response genes in infected worms and delays accumulation …

Testing Multiple Hypotheses Through Imp Weighted Fdr Based On A Genetic Functional Network With Application To A New Zebrafish Transcriptome Study, Jiang Gui, Casey S. Greene, Con Sullivan, Walter Taylor, Jason H. Moore, Carol Kim

Dartmouth Scholarship

In genome-wide studies, hundreds of thousands of hypothesis tests are performed simultaneously. Bonferroni correction and False Discovery Rate (FDR) can effectively control type I error but often yield a high false negative rate. We aim to develop a more powerful method to detect differentially expressed genes. We present a Weighted False Discovery Rate (WFDR) method that incorporate biological knowledge from genetic networks. We first identify weights using Integrative Multi-species Prediction (IMP) and then apply the weights in WFDR to identify differentially expressed genes through an IMP-WFDR algorithm. We performed a gene expression experiment to identify zebrafish genes that change expression …

Clustered Regularly Interspaced Short Palindromic Repeat-Dependent, Biofilm-Specific Death Of Pseudomonas Aeruginosa Mediated By Increased Expression Of Phage-Related Genes, Gary E. E. Heussler, Kyle C. Cady, Katja Koeppen, Sabin Bhuju, Bruce A. Stanton, George A. O’Toole

Dartmouth Scholarship

The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (CRISPR/Cas) system is an adaptive immune system present in many archaea and bacteria. CRISPR/Cas systems are incredibly diverse, and there is increasing evidence of CRISPR/Cas systems playing a role in cellular functions distinct from phage immunity. Previously, our laboratory reported one such alternate function in which the type 1-F CRISPR/Cas system of the opportunistic pathogen Pseudomonas aeruginosa strain UCBPP-PA14 (abbreviated as P. aeruginosa PA14) inhibits both biofilm formation and swarming motility when the bacterium is lysogenized by the bacteriophage DMS3. In this study, we demonstrated that the presence of just the DMS3 …

Early Inflammatory Mediator Gene Expression In Two Models Of Traumatic Brain Injury: Ex Vivo Cortical Slice In Mice And In Vivo Cortical Impact In Piglets, David J. Graber, Beth A. Costine, William F. Hickey

Dartmouth Scholarship

Background: The immunological response during the first 24 hours after traumatic brain injury (TBI) may be a critical therapeutic interval for limiting the secondary neuronal damage that is influenced by enhanced inflammatory mediator expression.

Methods: To gain further insight of the early injury response, we examined the expression of several inflammatory genes by real-time qPCR as a function of time or distance from injury in two distinct mammalian models: an ex vivo mouse cortical slice injury system and an in vivo piglet model of brain injury.

The Role Of Il-27 In Susceptibility To Post-Influenza Staphylococcus Aureus Pneumonia, Keven M. Robinson, Benjamin Lee, Erich V Scheller, Sivanarayana Mandalapu, Richard I. Enelow

Dartmouth Scholarship

Influenza is a common respiratory virus and Staphylococcus aureus frequently causes secondary pneumonia during influenza infection, leading to increased morbidity and mortality. Influenza has been found to attenuate subsequent Type 17 immunity, enhancing susceptibility to secondary bacterial infections. IL-27 is known to inhibit Type 17 immunity, suggesting a potential critical role for IL-27 in viral and bacterial co-infection.

In Vivo Cigarette Smoke Exposure Decreases Ccl20, Slpi, And Bd-1 Secretion By Human Primary Nasal Epithelial Cells, James Jukosky, Benoit J. Gosselin, Leah Foley, Tenzin Dechen, Steven Fiering, Mardi A. Crane-Godreau

Dartmouth Scholarship

Smokers and individuals exposed to second-hand cigarette smoke have a higher risk of developing chronic sinus and bronchial infections. This suggests that cigarette smoke (CS) has adverse effects on immune defenses against pathogens. Epithelial cells are important in airway innate immunity and are the first line of defense against infection. Airway epithelial cells not only form a physical barrier but also respond to the presence of microbes by secreting antimicrobials, cytokines, and chemokines. These molecules can lyse infectious microorganisms and/or provide signals critical to the initiation of adaptive immune responses. We examined the effects of CS on antimicrobial secretions of …

Increased Tissue Temperature Improves Electro-Transfer Mediated Gene Delivery To Skin, Anna Bulysheva, Amy Donate, Chelsea Edelblute, Derrick Jung, Karl Schoenbach, Richard Heller

Bioelectrics Publications

[Introduction] Developing an optimal gene electro-transfer system for delivery of plasmid DNA to the skin in vivo has been challenging with expression often confined in the epithelium requiring high voltage electric fields, which can cause cellular and tissue damage. Minimizing such damage, while optimizing gene expression profiles, are highly desirable for therapeutic applications of gene delivery to the skin. Cell membrane fluidity is temperature dependent, thus moderate temperature elevation can increase membrane fluidity. Utilizing this concept, we developed a novel gene electro-transfer electrode for in vivo applications with ability to heat tissue with a laser integrated into a four pin …

Defining The Role Of Trps1 In Phosphate Mediated Mineralization, Maria Kuzynski

All ETDs from UAB

Mineralization is a tightly controlled bi-phasic process that occurs when crystals of calcium and phosphate (Pi) are laid down within the extracellular matrix. However, the molecular networks regulating the initiation and progression of this process have not been well characterized. Pi, as one of the components of mineral crystals and a signaling molecule that regulates expression of mineralization-related genes, is essential to the mineralization process. In our studies, we discovered a novel function for Pi in this process: Pi is sufficient to induce secretion of matrix vesicles, which support the initiation of mineralization. Furthermore, we determined that this induction is …

Gene Expression And Alzheimer's Disease: Evaluation Of Gene Expression Patterns In Brain And Blood For An Alzheimer's Disease Mouse Model, Amanda Hazy

Senior Honors Theses

Previous studies have established a causative role for altered gene expression in development of Alzheimer’s disease (AD). These changes can be affected by methylation and miRNA regulation. In this study, expression of miRNA known to change methylation status in AD was assessed by qPCR. Genome-wide expression changes were determined by RNA-sequencing of mRNA from hippocampus and blood of control and AD mice. The qPCR data showed significantly increased expression of Mir 17 in AD, and sequencing data revealed 230 genes in hippocampus, 58 genes in blood, and 8 overlapping genes showing significant differential expression (p value ≤ 0.05). Expression data …

High-Throughput Data Analysis: Application To Micronuclei Frequency And T-Cell Receptor Sequencing, Mateusz Makowski

Theses and Dissertations

The advent of high-throughput sequencing has brought about the creation of an unprecedented amount of research data. Analytical methodology has not been able to keep pace with the plethora of data being produced. Two assays, ImmunoSEQ and the cytokinesisblock micronucleus (CBMN), that both produce count data and have few methods available to analyze them are considered.

ImmunoSEQ is a sequencing assay that measures the beta T-cell receptor (TCR) repertoire. The ImmunoSEQ assay was used to describe the TCR repertoires of patients that have undergone hematopoietic stem cell transplantation (HSCT). Several different methods for spectratype analysis were extended to the TCR …

Retracted - Quantitative Study Of Epigenetic Signature In Head And Necksquamous Cell Carcinoma, Ayesha Umair, Bassel Tarakji, Alzoghaibi Ibrahim, Azzeghaibi Nasser, Alenzi Fq, Ayesha Shreen

Turkish Journal of Medical Sciences

Background/aim: The aberrant upregulation of Forkhead box protein M1 (FOXM1) plays a fundamental role in cancer initiation by perturbing stem cell differentiation. This study aims to investigate the role of FOXM1 in epigenetic modification and gene expression of target genes in primary human oral keratinocytes, squamous cell carcinoma cell lines, and head and neck squamous cell carcinoma (HNSCC) tissue biopsies. Materials and methods: A genome-wide promoter methylation microarray was used to compare HNSCC cell line (n = 8), primary human oral keratinocytes (NOK; n = 8) transduced with FOXM1 and EGFP, and HNSCC tissue biopsies (n = 3). Seventeen Foxm1B-induced …