Medicine and Health Sciences Commons^™

Life-Shortening Wolbachia Infection Reduces Population Growth Of Aedes Aegypti, Eunho Suh, David R. Mercer, Stephen L. Dobson

Entomology Faculty Publications

Wolbachia bacteria are being introduced into natural populations of vector mosquitoes, with the goal of reducing the transmission of human diseases such as Zika and dengue fever. The successful establishment of Wolbachia infection is largely dependent on the effects of Wolbachia infection to host fitness, but the effects of Wolbachia infection on the individual life-history traits of immature mosquitoes can vary. Here, the effects of life-shortening Wolbachia (wMelPop) on population growth of infected individuals were evaluated by measuring larval survival, developmental time and adult size of Aedes aegypti in intra- (infected or uninfected only) and inter-group (mixed with …

A Platform For The Discovery And Characterization Of Proteins That Associate With Pseudomonas Aeruginosa Rna Polymerase, Danielle N. Brogren

All NMU Master's Theses

Pseudomonas aeruginosa is an opportunistic bacterial pathogen notable for its ability to colonize the lungs of cystic fibrosis patients. Once the bacterium infects and colonizes humans, it is extremely difficult to eradicate. This leads to long-term infections that significantly damage the lungs and other tissues. P. aeruginosa infections are challenging to treat due to the bacterium’s natural antibiotic resistance and the rise of multidrug resistant strains. Development of novel drug treatments are a necessity.

In all organisms, the regulation of gene expression is a highly controlled process. Remarkably, in P. aeruginosa bioinformatics studies showed that 20% of its genome is …

Effects Of Acute Sepsis On Renal Structure And Sympathetic Innervation In Mice, Tuqa Alkhateeb

Electronic Theses and Dissertations

Sympathetic nerves are important for renal physiology and sepsis pathophysiology. A recent study showed sprouting of sympathetic nerves in spleen of septic mice. This study was done to test if renal sprouting of sympathetic nerves also happens and to investigate renal morphology in septic mice. Cecal ligation and puncture (CLP) was used to induce sepsis and kidneys were removed for evaluation. Bowman’s space was diminished with cortical bubble cells present suggestive of acute renal pathology, however, renal function was unchanged. Acute sepsis did not affect either renal sympathetic innervation or non-neuronal cholinergic cells. Mouse kidneys had more epinephrine (EPI) than …

The Role Of Co-Opted Escrt Proteins And Lipid Factors In Protection Of Tombusviral Double-Stranded Rna Replication Intermediate Against Reconstituted Rnai In Yeast, Nikolay Kovalev, Jun-Ichi Inaba, Zhenghe Li, Peter D. Nagy

Plant Pathology Faculty Publications

Reconstituted antiviral defense pathway in surrogate host yeast is used as an intracellular probe to further our understanding of virus-host interactions and the role of co-opted host factors in formation of membrane-bound viral replicase complexes in protection of the viral RNA against ribonucleases. The inhibitory effect of the RNA interference (RNAi) machinery of S. castellii, which only consists of the two-component DCR1 and AGO1 genes, was measured against tomato bushy stunt virus (TBSV) in wild type and mutant yeasts. We show that deletion of the co-opted ESCRT-I (endosomal sorting complexes required for transport I) or ESCRT-III factors makes …

Crystal Structure Of Yersinia Pestis Virulence Factor Yfea Reveals Two Polyspecific Metal-Binding Sites, Christopher D. Radka, Lawrence J. Delucas, Landon S. Wilson, Matthew B. Lawrenz, Robert D. Perry, Stephen G. Aller

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Gram-negative bacteria use siderophores, outer membrane receptors, inner membrane transporters and substrate-binding proteins (SBPs) to transport transition metals through the periplasm. The SBPs share a similar protein fold that has undergone significant structural evolution to communicate with a variety of differentially regulated transporters in the cell. In Yersinia pestis, the causative agent of plague, YfeA (YPO2439, y1897), an SBP, is important for full virulence during mammalian infection. To better understand the role of YfeA in infection, crystal structures were determined under several environmental conditions with respect to transition-metal levels. Energy-dispersive X-ray spectroscopy and anomalous X-ray scattering data show that …

Circling The Drain: Regulating Nutrient Pollution From Agricultural Sources, William Gutermuth

Journal of Law and Health

The 2014 Toledo, Ohio tap water ban has, at least temporarily, put a spotlight on United States water supplies. Consequently, many Americans have begun to take a closer look at the quality of the fresh water bodies being used to supply tap water to their homes. Therefore, this Note analyzes the problems currently threatening the lakes, rivers, and other surface waters that are the source of fresh drinking water for huge populations in the United States. Part II examines the problem of nutrient pollution and explains the harmful effects it has on human health. Part III provides an overview of …

Characterization Of Transmembrane Protein 35 Expression: Considerations Of Sex And Ovarian Hormones, Amanda M. Vanderplow

All NMU Master's Theses

The recently discovered novel neuropeptide transmembrane protein 35 (TMEM35), is believed to modulate chemical signaling within the nervous system. Notably, the TMEM35 protein is detectable in humans, non-human primates and rodents, suggesting a conserved and critical function. Despite this, the functions of TMEM35 are ill-defined in the nervous system and insufficiently studied (currently only three publications). Previous work has identified high expression of TMEM35 in both the ventromedial hypothalamus (VMH) and the limbic circuit of the mouse brain. Due to the known functions of these two regions, this pattern of expression indicates possible roles of this neuropeptide in social behavior …

Rediscovery Of The Microtubule System In Chlamydomonas, Yi Liu

Dissertations (1934 -)

Extensive studies have revealed the complex mechanisms underlying the roles of the microtubule system in fundamental cellular processes, the severe consequences in development and health resulted from its anomaly, and the irreplaceable therapeutic agents that perturbs this vital yet inherently unstable cytoskeletal system. Most of the concepts derived from a handful of model organisms become dogma of the field despite contrary observations. By overcoming a major limitation of biflagellate green alga Chlamydomonas - the intense autofluorescence common to photosynthetic cells - this dissertation discovered new phenomena of the microtubule system and conceived an invention. The microtubule system of the green …

The Noncanonical Roles Of Two Primordial Molecules In Flagella, Xiaoyan Zhu

Dissertations (1934 -)

Motile cilia and flagella are ancient organelles that eukaryotic organisms today still rely on to thrive in their natural environment. Not surprisingly, accumulated evidence has shown that the intricate motility machinery, the microtubule-based axoneme, is evolutionarily conserved down to the molecular level. This notion is epitomized by the signature axonemal complex, the radial spoke (RS). The RS is part of a control center conferring the high frequency and tightly regulated movement. Key RS proteins discovered in biflagellate green alga, Chlamydomonas reinhardtii, are also generated by nearly all ciliated organisms, including Homo sapiens. Among them are two subunits from primordial protein …

Induction And Suppression Of Antiviral Rna Silencing By Tomato Spotted Wilt Virus, Sergio M. Gabriel Peralta

Department of Agronomy and Horticulture: Dissertations, Theses, and Student Research

Tomato spotted wilt virus (TSWV) is an emerging pathogen with wide host range and one of the most important viruses of plants. Information regarding processing of negative single stranded RNA viruses such as TSWV in the RNA silencing pathway remains limited. In nature TSWV is only transmitted by thrips as vectors and since infection occurs in both thrips and plants, an experimental system to transmit using thrips and the detection of TSWV were established. In order to understand the processing of TSWV in the RNA silencing pathway, Arabidopsis thaliana as a model plant was used in the genetic analysis against …

Freshwater Fungal Infections, Dennis J. Baumgardner

Dennis J. Baumgardner, MD

Fungal infections as a result of freshwater exposure or trauma are fortunately rare. Etiologic agents are varied, but commonly include filamentous fungi and Candida. This narrative review describes various sources of potential freshwater fungal exposure and the diseases that may result, including fungal keratitis, acute otitis externa and tinea pedis, as well as rare deep soft tissue or bone infections and pulmonary or central nervous system infections following traumatic freshwater exposure during natural disasters or near-drowning episodes. Fungal etiology should be suspected in appropriate scenarios when bacterial cultures or molecular tests are normal or when the infection worsens or fails …

Exploring The Impact Of Olfaction On Short-Term And Long-Term Maternal Recognition In Peromyscus Californicus, Mariah F. Conley

Honors Projects

Previous studies have established a connection between social behavior and olfaction, in that as anosmia causes a decrease in perception of social cues, social behavior itself decreases. Studies investigating maternal behavior specifically have focused on foster care, in which the behaviors formed during parturition are conserved and displayed with unrelated pups. The combination of long-term retention of maternal behavior, maternal recognition, and olfaction has yet to be explored. In this study, I induced anosmia in Peromyscus californicus, a monogamous, biparental species, and analyzed their behavior with their own pups and with foreign pups in the days after birth, as well …

Swainsonine Biosynthesis Genes In Diverse Symbiotic And Pathogenic Fungi, Daniel Cook, Bruno G. G. Donzelli, Rebecca Creamer, Deana L. Baucom, Dale R. Gardner, Juan Pan, Neil Moore, Stuart B. Krasnoff, Jerzy W. Jaromczyk, Christopher L. Schardl

Plant Pathology Faculty Publications

Swainsonine—a cytotoxic fungal alkaloid and a potential cancer therapy drug—is produced by the insect pathogen and plant symbiont Metarhizium robertsii, the clover pathogen Slafractonia leguminicola, locoweed symbionts belonging to Alternaria sect. Undifilum, and a recently discovered morning glory symbiont belonging to order Chaetothyriales. Genome sequence analyses revealed that these fungi share orthologous gene clusters, designated “SWN,” which included a multifunctional swnKgene comprising predicted adenylylation and acyltransferase domains with their associated thiolation domains, a β-ketoacyl synthase domain, and two reductase domains. The role of swnK was demonstrated by inactivating it in M. robertsii through homologous …

Zinc Transporters Ybtx And Znuabc Are Required For The Virulence Of Yersinia Pestis In Bubonic And Pneumonic Plague In Mice, Alexander G. Bobrov, Olga Kirillina, Marina Y. Fosso, Jacqueline D. Fetherston, M. Clarke Miller, Tiva T. Vancleave, Joseph A. Burlison, William K. Arnold, Matthew B. Lawrenz, Sylvie Garneau-Tsodikova, Robert D. Perry

Microbiology, Immunology, and Molecular Genetics Faculty Publications

A number of bacterial pathogens require the ZnuABC Zinc (Zn²⁺) transporter and/or a second Zn²⁺ transport system to overcome Zn²⁺ sequestration by mammalian hosts. Previously we have shown that in addition to ZnuABC, Yersinia pestis possesses a second Zn²⁺ transporter that involves components of the yersiniabactin (Ybt), siderophore-dependent iron transport system. Synthesis of the Ybt siderophore and YbtX, a member of the major facilitator superfamily, are both critical components of the second Zn²⁺ transport system. Here we demonstrate that a ybtX znu double mutant is essentially avirulent in mouse models of bubonic and pneumonic …

An Analysis Of Neurogenesis In A Mouse Model Of Chemotherapy Related Cognitive Impairment, Maxwell A. Hennings

Electronic Theses and Dissertations

Cancer patients treated with adjuvant chemotherapy often experience cognitive decline following treatment. This phenomenon, often dubbed “chemo brain” or “chemo fog” is usually temporary, but for a subset of survivors, these cognitive impairments can be long-lasting (>10 years) and negatively affect patients’ quality of life, career performance, and social fulfillment. While it is unclear what neurobiological mechanisms underlie chemotherapy related cognitive impairment, the majority of the animal literature has focused on adult neurogenesis. One process important for neurogenesis is the proliferation of new neurons within the dentate gyrus of the hippocampus. It is evident that many chemotherapy agents can …

Identification Of Intrahelical Bifurcated H‑Bonds As A New Type Of Gate In K+ Channels, Oliver Rauh, Martin Urban, Leonhard M. Henkes, Tobias Winterstein, Timo Greiner, James L. Van Etten, Anna Moroni, Stefan M. Kast, Gerhard Thiel, Indra Schroeder

James Van Etten Publications

Gating of ion channels is based on structural transitions between open and closed states. To uncover the chemical basis of individual gates, we performed a comparative experimental and computational analysis between two K⁺ channels, Kcv_S and Kcv_NTS. These small viral encoded K+ channel proteins, with a monomer size of only 82 amino acids, resemble the pore module of all complex K+ channels in terms of structure and function. Even though both proteins share about 90% amino acid sequence identity, they exhibit different open probabilities with ca. 90% in Kcv_NTS and 40% in Kcv_S. …

Lymphoid Hematopoiesis And The Role Of B-Cells In Transgenic Mouse Model Of Sickle Cell Disease, Christina Cotte

University Scholar Projects

Sickle cell disease (SCD) has been shown to be associated with decreased baseline immunity and thus increased susceptibility to infection. I sought to discern possible causes of this by looking into the correlations between SCD and hematopoiesis, the immune system and the neuroendocrine system, and ultimately by conducting experiments surrounding the impaired immune system of SCD. These experiments focused on the potential causes and effects of the diminution of B-1a cells in the SCD spleen. Adoptive transfers, infections with Streptococcus pneumoniae, and histologic imaging were conducted to establish if the diminution of the B-1a cells in the SCD spleen …

Are Cdi Systems Multicolored, Facultative, Helping Greenbeards?, Elizabeth S. Danka, Erin C. Garcia, Peggy A. Cotter

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Competitive and cooperative interactions between organisms, including bacteria, can significantly impact the composition of a community and the fitness of its members, as well as the fitness of their hosts when communities are living on or within other organisms. Understanding the underlying mechanisms is critical to the development of strategies to control microbiological communities that impact animal and plant health and also for understanding the evolution of social behaviors, which has been challenging for evolutionary biologists. Contact-dependent growth inhibition (CDI) is a phenomenon defined by the delivery of a protein toxin to the cytoplasm of neighboring bacteria upon cell–cell contact, …

Chat Expression In Chlamydia Muridarum-Infected Female Murine Genital Tract, Hallie Sartain

Undergraduate Honors Theses

Chlamydia trachomatis is the most prevalent agent of bacterial sexually transmitted infections in the world. However, a profuse number of cases are unreported, as the infection is often asymptomatic. Sequelae such as pelvic inflammatory disease, an increased risk of cervical cancer, premature birth, and perinatal infections in pregnant women can occur. Inflammation occurs in the body in response to infection or injury. Although inflammation can lead to some unwanted secondary effects, such as pain, it serves to return the body to homeostasis by restoring injured tissues and eliminating pathogens. One recently identified connection between the central nervous system and the …

Determination Of The Effects That A Previously Uncharacterized Secreted Product From Klebsiella Pneumoniae Has On Citrobacter Freundii And Enterobacter Cloacae Biofilms, Cody M. Hastings

Undergraduate Honors Theses

More so than ever, Multiple Drug Resistant (MDR) bacteria are on the rise due to overuse of antibiotics along with natural selection for adaptations that enhance drug-resistant properties. One particular bacterial family, Enterobacteriaceae, has been problematic, exhibiting several bacterial members that have developed a precipitous resistance to modern antibiotics and are also primary causative agents of nosocomial, or hospital acquired, infections. Citrobacter freundii (CF) and Enterobacter cloacae (ECL) are two species of the Enterobacteriaceae family causing significant medical concern due to their role in producing numerous opportunistic infections such as bacteremia, lower respiratory tract infections, urinary tract infections, and endocarditis. …

Range-Wide Prevalence And Impacts Of Pseudocercosporella Inconspicua On Lilium Grayi And An Assessment Of L. Superbum And L. Michauxii As Reservoirs, Cindy L. Barrett

Electronic Theses and Dissertations

Lilium grayi (Gray’s Lily), a southern Appalachian endemic species, is threatened by a Lilium-specific fungal pathogen, Pseudocercosporella inconspicua. The disease is characterized by tan lesions that can cause early senescence, while also lowering seed production and viability. This project tested for P. inconspicua conidia and accessed health at nine locations. The disease was present and ubiquitous across the range of L. grayi. Through identification of P. inconspicua conidia in the field, L. superbum (Turk’s Cap Lily) was identified as an additional host, while L. michauxii (Michaux’s Lily) was disease-free. However, infection was inducible in both species. With …

Pharmacodynamic Activity Of Fosfomycin Simulating Urinary Concentrations Achieved After A Single 3 Gram Oral Dose Versus Escherichia Coli Using An In Vitro Model, George G. Zhanel, Kate Parkinson, Sean Higgins, Andrew Denisuik, Heather Adam, Johann Pitout, Ayman Noreddin, James A. Karlowsky

Pharmacy Faculty Articles and Research

We assessed the activity of fosfomycin simulating urinary concentrations achieved after a single 3 gram oral dose against Escherichia coli using an in vitro pharmacodynamic model. Eleven urinary isolates of E. coli were studied. Isolates were ESBL-producing or carbapenemase-producing. The in vitro pharmacodynamic model was inoculated with an inoculum of (~1 × 10⁶ cfu/mL). Fosfomycin was administered to simulate maximum free (ƒ) urine (U) concentrations and a t_1/2 obtained after a standard single 3 gram oral dose in healthy volunteers (ƒU_max, 4000 mg/L; t_1/2, 6 h). Sampling was performed over 48 h to assess …

The Effects Of A Hpv Educational Intervention Aimed At Collegiate Males On Knowledge, Vaccine Intention, And Uptake, Mary A. Knudtson

Evidence-Based Practice Project Reports

Human Papillomavirus (HPV) is the most common sexually transmitted infection (STI) in the United States (US). In 2013, approximately 6% of 19 to 26-year-old males had received at least one dose of the HPV vaccine (Richman, Maddy, Torres, & Goldberg, 2016). Currently there is no known cure for HPV, however a prophylactic vaccination provides an efficacious method for protection against HPV related diseases. The purpose of the evidence-based project was to provide a HPV educational intervention to collegiate males and examine the effects of HPV knowledge, intention to vaccinate, and receipt of vaccination. The Health Belief Model was selected to …

Thinking Pigs: Cognition, Emotion, And Personality, Lori Marino, Christina M. Colvin

Lori Marino, PhD

An exploration of the cognitive complexity of Sus domesticus, the domestic pig.

Granting Personhood For Sentient Non-Human Animals And Sentient Artificial Intelligences: A Demonstrative Argument, Jeremiah Meadows

Virginias Collegiate Honors Council Conference

While the subject of personhood has been exhaustively debated regarding the unborn, personhood for sentient animals and artificial intelligences is a concept that is rarely deliberated. Humanity has learned that there are multiple animal species which are very similar to humans in their self-awareness, emotional capacity, and free will. These traits have been partially developed for artificial intelligences as well, and those characteristics will evolve alongside human and technological development. As stratified societies emerged, there have been multiple occurrences where individuals were deemed lesser but then later acquired equal standing. Dr. Daniel Wilson, roboticist, wrote in his novel Robopocalypse, “It …

Thujone Inhibits The Function Of Α7-Nicotinic Acetylcholine Receptors And Impairs Nicotine-Induced Memory Enhancement In One-Trial Passive Avoidance Paradigm, Ahmed Sultan, Keun-Hang Susan Yang, Dmytro Isaev, Eslam El Nebrisi, Nurulain Syed, Nadia Khan, Christopher F. Howarth, Bassem Sadek, Murat Oz

Mathematics, Physics, and Computer Science Faculty Articles and Research

Effects of thujone, a major ingredient of absinthe, wormwood oil and some herbal medicines, were tested on the function of α7 subunit of the human nicotinic acetylcholine (α7 nACh) receptor expressed in Xenopus oocytes using the two-electrode voltage-clamp technique. Thujone reversibly inhibited ACh (100 μM)-induced currents with an IC50 value of 24.7 μM. The effect of thujone was not dependent on the membrane potential and did not involve Ca2+-dependent Cl- channels expressed endogenously in oocytes. Inhibition by thujone was not reversed by increasing ACh concentrations. Moreover, specific binding of [125I] -bungarotoxin was not altered by thujone. Further experiments in SH-EP1 …

Distribution Of Diverse Escherichia Coli Between Cattle And Pasture, Volker Brozel

Volker Brozel

Targeted Aav5-Smad7 Gene Therapy Inhibits Corneal Scarring In Vivo, Suneel Gupta, Jason T. Rodier, Ajay Sharma, Elizabeth A. Giuliano, Prashant R. Sinha, Nathan P. Hesemann, Arkasubhra Ghosh, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Corneal scarring is due to aberrant activity of the transforming growth factor β (TGFβ) signaling pathway following traumatic, mechanical, infectious, or surgical injury. Altered TGFβ signaling cascade leads to downstream Smad (Suppressor of mothers against decapentaplegic) protein-mediated signaling events that regulate expression of extracellular matrix and myogenic proteins. These events lead to transdifferentiation of keratocytes into myofibroblasts through fibroblasts and often results in permanent corneal scarring. Hence, therapeutic targets that reduce transdifferentiation of fibroblasts into myofibroblasts may provide a clinically relevant approach to treat corneal fibrosis and improve long-term visual outcomes. Smad7 protein regulates the functional effects of TGFβ signaling …

Virus-Mediated Suppression Of Host Non-Self Recognition Facilitates Horizontal Transmission Of Heterologous Viruses, Songsong Wu, Jiasen Cheng, Yanping Fu, Tao Chen, Daohong Jiang, Said A. Ghabrial, Jiatao Xie

Plant Pathology Faculty Publications

Non-self recognition is a common phenomenon among organisms; it often leads to innate immunity to prevent the invasion of parasites and maintain the genetic polymorphism of organisms. Fungal vegetative incompatibility is a type of non-self recognition which often induces programmed cell death (PCD) and restricts the spread of molecular parasites. It is not clearly known whether virus infection could attenuate non-self recognition among host individuals to facilitate its spread. Here, we report that a hypovirulence-associated mycoreovirus, named Sclerotinia sclerotiorum mycoreovirus 4 (SsMYRV4), could suppress host non-self recognition and facilitate horizontal transmission of heterologous viruses. We found that cell death in …

Draft Genome Sequence Of Cercospora Sojina Isolate S9, A Fungus Causing Frogeye Leaf Spot (Fls) Disease Of Soybean, Fanchang Zeng, Chaofan Wang, Guirong Zhang, Junmei Wei, Carl A. Bradley, Ray Ming

Plant Pathology Faculty Publications

Fungi are the causal agents of many of the world's most serious plant diseases causing disastrous consequences for large-scale agricultural production. Pathogenicity genomic basis is complex in fungi as multicellular eukaryotic pathogens. The fungus Cercospora sojina is a plant pathogen that threatens global soybean supplies. Here, we report the genome sequence of C. sojina strain S9 and detect genome features and predicted genomic elements. The genome sequence of C. sojina is a valuable resource with potential in studying the fungal pathogenicity and soybean host resistance to frogeye leaf spot (FLS), which is caused by C. sojina. …