Digital Commons Network^™

Identification Of Ecdysone Hormone Receptor Agonists As A Therapeutic Approach For Treating Filarial Infections, Amruta S Mhashilkar, Sai L Vankayala, Canhui Liu, Fiona Kearns, Priyanka Mehrotra, George Tzertzinis, Subba R Palli, H. Lee Woodcock Iii, Thomas R Unnasch

Chemistry Faculty Publications

BACKGROUND: A homologue of the ecdysone receptor has previously been identified in human filarial parasites. As the ecdysone receptor is not found in vertebrates, it and the regulatory pathways it controls represent attractive potential chemotherapeutic targets.

METHODOLOGY/ PRINCIPAL FINDINGS: Administration of 20-hydroxyecdysone to gerbils infected with B. malayi infective larvae disrupted their development to adult stage parasites. A stable mammalian cell line was created incorporating the B. malayi ecdysone receptor ligand-binding domain, its heterodimer partner and a secreted luciferase reporter in HEK293 cells. This was employed to screen a series of ecdysone agonist, identifying seven agonists active at sub-micromolar concentrations. …

Identification Of Ecdysone Hormone Receptor Agonists As A Therapeutic Approach For Treating Filarial Infections, Amruta S. Mhashilkar, Sai L. Vankayala, Canhui Liu, Fiona Kearns, Priyanka Mehrotra, George Tzertzinis, Subba R. Palli, H. Lee Woodcock, Thomas R. Unnasch

Entomology Faculty Publications

Background A homologue of the ecdysone receptor has previously been identified in human filarial parasites. As the ecdysone receptor is not found in vertebrates, it and the regulatory pathways it controls represent attractive potential chemotherapeutic targets.

Methodology/ Principal Findings Administration of 20-hydroxyecdysone to gerbils infected with B. malayi infective larvae disrupted their development to adult stage parasites. A stable mammalian cell line was created incorporating the B. malayi ecdysone receptor ligand-binding domain, its heterodimer partner and a secreted luciferase reporter in HEK293 cells. This was employed to screen a series of ecdysone agonist, identifying seven agonists active at …

Multiorgan Chronic Inflammatory Hepatobiliary Pancreatic Murine Model Deficient In Tumor Necrosis Factor Receptors 1 And 2, Helieh S. Oz

Physiology Faculty Publications

AIM: To provoke persistent/chronic multiorgan inflammatory response and to contribute to stones formation followed by fibrosis in hepatobiliary and pancreatic tissues.

METHODS: Tumor necrosis factor receptors 1 and 2 (TNFR1/R2) deficient mice reared in-house were given dibutyltin dichloride (DBTC) twice within 10 d by oral gavage delivery. Sham control animals received vehicle treatment and naïve animals remained untreated throughout the study. Animals were monitored daily for symptoms of pain and discomfort. The abdominal and hindpaw hypersensitivity were assessed with von Frey microfilaments. Exploratory behaviors were recorded at the baseline, after initiation of treatment, and before study termination. Histopathological …

Framework For Drafting Ecological Objectives For Water Sharing Plans - Submission Of The Nsw Aboriginal Land Council, Geoff Scott, New South Wales Aboriginal Land Council

Indigenous Water Justice Symposium (June 6)

Presenter: Phil Duncan, Gomeroi Nation, New South Wales Aboriginal Land Council

4 pages

Contains 1 footnote

Letter addressed to Nick Cook, A/Team Leader, WSP Science & Evaluation - North, NSW Office of Water, from Geoff Scott, Chief Executive Officer, New South Wales Aboriginal Land Council.

Threatening Animals?, Heather I. Sullivan

Modern Languages and Literatures Faculty Research

Threatening predators and pernicious beasts continue to play significant roles in the human imaginary even as human threats to other species increase exponentially in the age of Anthropocene. While posthumanist animal studies and material ecocriticism sync human and other animals within the biosphere’s living interactions, our shared material reciprocity is currently skewing ever more towards the human threat to other species – and so to ourselves as co-dependents. This essay explores the meaning of “threatening” and “threatened”. Five German texts presenting human-animal interactions in the Anthropocene’s span by Goethe, Kafka, Stifter, Duve, and Trojanow unsettle expectations of threats. In Goethe’s …

Associative Spike Timing-Dependent Potentiation Of The Basal Dendritic Excitatory Synapses In The Hippocampus In Vivo., Thomas K Fung, Clayton S Law, L Stan Leung

Physiology and Pharmacology Publications

Spike timing-dependent plasticity in the hippocampus has rarely been studied in vivo. Using extracellular potential and current source density analysis in urethane-anesthetized adult rats, we studied synaptic plasticity at the basal dendritic excitatory synapse in CA1 after excitation-spike (ES) pairing; E was a weak basal dendritic excitation evoked by stratum oriens stimulation, and S was a population spike evoked by stratum radiatum apical dendritic excitation. We hypothesize that positive ES pairing-generating synaptic excitation before a spike-results in long-term potentiation (LTP) while negative ES pairing results in long-term depression (LTD). Pairing (50 pairs at 5 Hz) at ES intervals of -10 …

Reproductive Arrest And Stress Resistance In Winter-Acclimated Drosophila Suzukii., Jantina Toxopeus, Ruth Jakobs, Laura V Ferguson, Tara D Gariepy, Brent J Sinclair

Biology Publications

Overwintering insects must survive the multiple-stress environment of winter, which includes low temperatures, reduced food and water availability, and cold-active pathogens. Many insects overwinter in diapause, a developmental arrest associated with high stress tolerance. Drosophila suzukii (Diptera: Drosophilidae), spotted wing drosophila, is an invasive agricultural pest worldwide. Its ability to overwinter and therefore establish in temperate regions could have severe implications for fruit crop industries. We demonstrate here that laboratory populations of Canadian D. suzukii larvae reared under short-day, low temperature, conditions develop into dark 'winter morph' adults similar to those reported globally from field captures, and observed by us …

Expression And Function Of Pannexins In The Inner Ear And Hearing, Hong-Bo Zhao

Otolaryngology--Head & Neck Surgery Faculty Publications

Pannexin (Panx) is a gene family encoding gap junction proteins in vertebrates. So far, three isoforms (Panx1, 2 and 3) have been identified. All of three Panx isoforms express in the cochlea with distinct expression patterns. Panx1 expresses in the cochlea extensively, including the spiral limbus, the organ of Corti, and the cochlear lateral wall, whereas Panx2 and Panx3 restrict to the basal cells of the stria vascularis in the lateral wall and the cochlear bony structure, respectively. However, there is no pannexin expression in auditory sensory hair cells. Recent studies demonstrated that like connexin gap junction gene, Panx1 deficiency …

Enhancement Of Aging Rat Laryngeal Muscles With Endogenous Growth Factor Treatment, Joseph C. Stemple, Richard D. Andreatta, Tanya S. Seward, Vrushali Angadi, Maria Dietrich, Colleen A. Mcmullen

Physical Therapy Faculty Publications

Clinical evidence suggests that laryngeal muscle dysfunction is associated with human aging. Studies in animal models have reported morphological changes consistent with denervation in laryngeal muscles with age. Life‐long laryngeal muscle activity relies on cytoskeletal integrity and nerve–muscle communication at the neuromuscular junction (NMJ). It is thought that neurotrophins enhance neuromuscular transmission by increasing neurotransmitter release. We hypothesized that treatment with neurotrophin 4 (NTF4) would modify the morphology and functional innervation of aging rat laryngeal muscles. Fifty‐six Fischer 344xBrown Norway rats (6‐ and 30‐mo age groups) were used to evaluate to determine if NTF4, given systemically (n = 32) …

Thrombospondin 1 Deficiency Ameliorates The Development Of Adriamycin-Induced Proteinuric Kidney Disease, Hasiyeti Maimaitiyiming, Qi Zhou, Shuxia Wang

Pharmacology and Nutritional Sciences Faculty Publications

Accumulating evidence suggests that thrombospondin 1 (TSP1) is an important player in diabetic nephropathy. However, the role of TSP1 in podocyte injury and the development of non-diabetic proteinuric kidney disease is largely unknown. In the current study, by using a well-established podocyte injury model (adriamycin-induced nephropathy mouse model), we examined the contribution of TSP1 to the development of proteinuric kidney disease. We found that TSP1 was up-regulated in the glomeruli, notably in podocytes, in adriamycin injected mice before the onset of proteinuria. ADR treatment also stimulated TSP1 expression in cultured human podocytes in vitro. Moreover, increased TSP1 mediated ADR-induced …

Ubr3, A Novel Modulator Of Hh Signaling Affects The Degradation Of Costal-2 And Kif7 Through Poly-Ubiquitination, Tongchao Li, Junkai Fan, Bernardo Blanco-Sánchez, Nikolaos Giagtzoglou, Guang Lin, Shinya Yamamoto, Manish Jaiswal, Kuchuan Chen, Jie Zhang, Wei Wei, Michael T. Lewis, Andrew K. Groves, Monte Westerfield, Jianhang Jia, Hugo J. Bellen

Markey Cancer Center Faculty Publications

Hedgehog (Hh) signaling regulates multiple aspects of metazoan development and tissue homeostasis, and is constitutively active in numerous cancers. We identified Ubr3, an E3 ubiquitin ligase, as a novel, positive regulator of Hh signaling in Drosophila and vertebrates. Hh signaling regulates the Ubr3-mediated poly-ubiquitination and degradation of Cos2, a central component of Hh signaling. In developing Drosophila eye discs, loss of ubr3 leads to a delayed differentiation of photoreceptors and a reduction in Hh signaling. In zebrafish, loss of Ubr3 causes a decrease in Shh signaling in the developing eyes, somites, and sensory neurons. However, not all tissues that require …

Diffuse Traumatic Brain Injury Induces Prolonged Immune Sysregulation And Potentiates Hyperalgesia Following A Peripheral Immune Challenge, Rachel K. Rowe, Gavin I. Ellis, Jordan L. Harrison, Adam D. Bachstetter, Gregory F. Corder, Linda J. Van Eldik, Bradley K. Taylor, Francesc Marti, Jonathan Lifshitz

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Background: Nociceptive and neuropathic pain occurs as part of the disease process after traumatic brain injury (TBI) in humans. Central and peripheral inflammation, a major secondary injury process initiated by the traumatic brain injury event, has been implicated in the potentiation of peripheral nociceptive pain. We hypothesized that the inflammatory response to diffuse traumatic brain injury potentiates persistent pain through prolonged immune dysregulation.

Results: To test this, adult, male C57BL/6 mice were subjected to midline fluid percussion brain injury or to sham procedure. One cohort of mice was analyzed for inflammation-related cytokine levels in cortical biopsies and serum along an …

The Tnfα-Transgenic Rat: Hippocampal Synaptic Integrity, Cognition, Function, And Post-Ischemic Cell Loss, L. Creed Pettigrew, Richard J. Kryscio, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

The cytokine, tumor necrosis factor α (TNFα), is a key regulator of neuroinflammation linked to numerous neurodegenerative conditions and diseases. The present study used transgenic rats that overexpress a murine TNFα gene, under the control of its own promoter, to investigate the impact of chronically elevated TNFα on hippocampal synaptic function. Neuronal viability and cognitive recovery in TNFα Tg rats were also determined following an ischemic insult arising from reversible middle cerebral artery occlusion (MCAO). Basal CA3-CA1 synaptic strength, recorded in acute brain slices, was not significantly different between eight-week-old TNFα Tg rats and non-Tg rats. In contrast, slices from …

Single-Cell Transcriptional Analysis Of Normal, Aberrant, And Malignant Hematopoiesis In Zebrafish, Finola E. Moore, Elaine G. Garcia, Riadh Lobbardi, Esha Jain, Qin Tang, John C. Moore, Mauricio Cortes, Aleksey Molodtsov, Melissa Kasheta, Christina C. Luo, Amaris J. Garcia, Ravi Mylvaganam, Jeffrey A. Yoder, Jessica S. Blackburn, Ruslan I. Sadreyev, Craig J. Ceol, Trista E. North, David M. Langenau

Molecular and Cellular Biochemistry Faculty Publications

Hematopoiesis culminates in the production of functionally heterogeneous blood cell types. In zebrafish, the lack of cell surface antibodies has compelled researchers to use fluorescent transgenic reporter lines to label specific blood cell fractions. However, these approaches are limited by the availability of transgenic lines and fluorescent protein combinations that can be distinguished. Here, we have transcriptionally profiled single hematopoietic cells from zebrafish to define erythroid, myeloid, B, and T cell lineages. We also used our approach to identify hematopoietic stem and progenitor cells and a novel NK-lysin 4⁺ cell type, representing a putative cytotoxic T/NK cell. Our platform …

Calpain-5 Expression In The Retina Localizes To Photoreceptor Synapses, Kellie A. Schaefer, Marcus A. Toral, Gabriel Velez, Allison J. Cox, Sheila A. Baker, Nicholas C. Borcherding, Diana F. Colgan, Vimala Bondada, Charles B. Mashburn, Chen Guang Yu, James W. Geddes, Stephen H. Tsang, Alexander G. Bassuk, Vinit B. Mahajan

Spinal Cord and Brain Injury Research Center Faculty Publications

Purpose: We characterize calpain-5 (CAPN5) expression in retinal and neuronal subcellular compartments.

Methods: CAPN5 gene variants were classified using the exome variant server, and RNA-sequencing was used to compare expression of CAPN5 mRNA in the mouse and human retina and in retinoblastoma cells. Expression of CAPN5 protein was ascertained in humans and mice in silico, in mouse retina by immunohistochemistry, and in neuronal cancer cell lines and fractionated central nervous system tissue extracts by Western analysis with eight antibodies targeting different CAPN5 regions.

Results: Most CAPN5 genetic variation occurs outside its protease core; and searches …

A Conserved Dna Repeat Promotes Selection Of A Diverse Repertoire Of Trypanosoma Brucei Surface Antigens From The Genomic Archive., Galadriel Hovel-Miner, Monica R Mugnier, Benjamin Goldwater, George A M Cross, F Nina Papavasiliou

Microbiology, Immunology, and Tropical Medicine Faculty Publications

African trypanosomes are mammalian pathogens that must regularly change their protein coat to survive in the host bloodstream. Chronic trypanosome infections are potentiated by their ability to access a deep genomic repertoire of Variant Surface Glycoprotein (VSG) genes and switch from the expression of one VSG to another. Switching VSG expression is largely based in DNA recombination events that result in chromosome translocations between an acceptor site, which houses the actively transcribed VSG, and a donor gene, drawn from an archive of more than 2,000 silent VSGs. One element implicated in these duplicative gene conversion events is a DNA repeat …

Paradoxical Acclimation Responses In The Thermal Performance Of Insect Immunity., Laura V Ferguson, David E Heinrichs, Brent J Sinclair

Biology Publications

Winter is accompanied by multiple stressors, and the interactions between cold and pathogen stress potentially determine the overwintering success of insects. Thus, it is necessary to explore the thermal performance of the insect immune system. We cold-acclimated spring field crickets, Gryllus veletis, to 6 °C for 7 days and measured the thermal performance of potential (lysozyme and phenoloxidase activity) and realised (bacterial clearance and melanisation) immune responses. Cold acclimation decreased the critical thermal minimum from -0.5 ± 0.25 to -2.1 ± 0.18 °C, and chill coma recovery time after 72 h at -2 °C from 16.8 ± 4.9 to 5.2 …

Paradoxical Acclimation Responses In The Thermal Performance Of Insect Immunity., Laura V Ferguson, David E Heinrichs, Brent J Sinclair

Biology Publications

Winter is accompanied by multiple stressors, and the interactions between cold and pathogen stress potentially determine the overwintering success of insects. Thus, it is necessary to explore the thermal performance of the insect immune system. We cold-acclimated spring field crickets, Gryllus veletis, to 6 °C for 7 days and measured the thermal performance of potential (lysozyme and phenoloxidase activity) and realised (bacterial clearance and melanisation) immune responses. Cold acclimation decreased the critical thermal minimum from -0.5 ± 0.25 to -2.1 ± 0.18 °C, and chill coma recovery time after 72 h at -2 °C from 16.8 ± 4.9 to 5.2 …

Strange And Unstable Bodies: Shifting Materialities In Early American Natural History Correspondence Networks, Julie Marie Mccown

English Dissertations - Archive

This dissertation fills a gap in the study of early American natural history literature by investigating the representation of animal bodies within early American natural history writing and attending to the role animal bodies play in shaping natural history knowledge and how natural history in turn shapes animal bodies. It also examines the effect the shifting materiality of animal bodies has on constructions of race and ethnicity in early America, as well as the ways non-white, non-male, and non-human persons exercise agency via natural history correspondence networks. Employing animal studies, posthumanism, and new materialism, I contend that, within natural history’s …

Characterization Of A Silac Method For Proteomic Analysis Of Primary Rat Microglia, Ping Zhang, Ashley E. Culver-Cochran, Stanley M. Stevens Jr., Bin Liu

Molecular Biosciences Faculty Publications

Microglia play important and dynamic roles in mediating a variety of physiological and pathological processes during the development, normal function and degeneration of the central nervous system. Application of SILAC-based proteomic analysis would greatly facilitate the identification of cellular pathways regulating the multifaceted phenotypes of microglia. We and others have successfully SILAC-labeled immortalized murine microglial cell lines in previous studies. In this study, we report the development and evaluation of a SILAC-labeled primary rat microglia model. Although the isotope labeling scheme for primary microglia is drastically different from that of immortalized cell lines, our de novo and uninterrupted primary culture …

Video Campaign On Behalf Of The Rispca, Kara M. Guezze

Senior Honors Projects

According to the American Society for the Prevention of Cruelty to Animals, it is estimated that 70-80 million dogs and 74-96 million cats are owned in the United States. It is impossible to determine how many stray dogs and cats live in the US, but estimates for cats alone range up to 70 million. There will always be a need for the protection and care of stray, abandoned, and abused animals, as well as management of their population. These companion animals are our best friends and have easily integrated into our families over the years. For over 146 years, the …

Influence Of Daily Social Stimulation On Behavioral And Physiological Outcomes In An Animal Model Of Ptsd., Shyam Seetharaman, Monika Fleshner, Collin R. Park, David M. Diamond

Psychology Faculty Publications

INTRODUCTION: We have shown in previous work that acute episodes of predator exposure occurring in the context of chronic social instability produced PTSD-like sequelae in rats. Our animal model of PTSD contained two components: (1) acute trauma, immobilization of rats in close proximity to a cat twice in 10 days, and (2) chronic social instability, 31 days of randomized housing of cage cohorts. Here we tested the hypothesis that daily social stimulation would block the development of the PTSD-like sequelae.

METHODS: Beginning 24 h after the first cat exposure, adult male rats were given our established PTSD model, alone or …

Capturing The Phylogeny Of Holometabola With Mitochondrial Genome Data And Bayesian Site-Heterogeneous Mixture Models, Fan Song, Hu Li, Pei Jiang, Xuguo Zhou, Jinpeng Liu, Changhai Sun, Alfried P. Vogler, Wanzhi Cai

Entomology Faculty Publications

After decades of debate, a mostly satisfactory resolution of relationships among the 11 recognized holometabolan orders of insects has been reached based on nuclear genes, resolving one of the most substantial branches of the tree-of-life, but the relationships are still not well established with mitochondrial genome data. The main reasons have been the absence of sufficient data in several orders and lack of appropriate phylogenetic methods that avoid the systematic errors from compositional and mutational biases in insect mitochondrial genomes. In this study, we assembled the richest taxon sampling of Holometabola to date (199 species in 11 orders), and analyzed …

The Fire In The Firefly: The Unspoken (Speaks), Ania S. Payne

All NMU Master's Theses

This collection of nonfiction essays explores life and the way that we, as animals—humans, mammals, insects—engage the world that we all share together, both from a personal perspective and from a distant, 3^rd person perspective. Some of these essays dabble in memoir, wherein I closely examine the intricacies of the relationships between my family members, neighbors, and friends. Other essays are driven by research and my relentless curiosity about the world around me—what goes on in the mind of the earthworm or chigger, the science of fear and the inevitability of death that surrounds us all. This collective narrative …

Kindred, Katelyn Osborne

Electronic Theses and Dissertations

Kindred, an MFA exhibition held at the Tipton Gallery located in downtown Johnson City from Feburary 22^nd to March 4^th. Kindred presents two bodies of work, which are a collection of drawings, etchings, monoprints, and lithographs, that center around a personal mythology and symbolism of self-identity and discovery. These works explore the physical and spiritual connection behind being a fraternal twin through the metaphorical use of animal imagery.

The ideas discussed in this paper center around the process of creating a personal mythology and symbolism through my observations of animals and how I relate that experience to …

A One Health Message About Bats Increases Intentions To Follow Public Health Guidance On Bat Rabies, Hang Lu, Katherine A. Mccomas, Danielle E. Buttke, Sungjong Roh, Margaret A. Wild

Research Collection Lee Kong Chian School Of Business

Since 1960, bat rabies variants have become the greatest source of human rabies deaths in the United States. Improving rabies awareness and preventing human exposure to rabid bats remains a national public health priority today. Concurrently, conservation of bats and the ecosystem benefits they provide is of increasing importance due to declining populations of many bat species. This study used a visitor-intercept experiment (N = 521) in two U.S. national parks where human and bat interactions occur on an occasional basis to examine the relative persuasiveness of four messages differing in the provision of benefit and uncertainty information on intentions …

Effect Of Dietary Starch Source And Concentration On Equine Fecal Microbiota, Brittany E. Harlow, Laurie M. Lawrence, Susan H. Hayes, Andrea Crum, Michael D. Flythe

Animal and Food Sciences Faculty Publications

Starch from corn is less susceptible to equine small intestinal digestion than starch from oats, and starch that reaches the hindgut can be utilized by the microbiota. The objective of the current study was to examine the effects of starch source on equine fecal microbiota. Thirty horses were assigned to treatments: control (hay only), HC (high corn), HO (high oats), LC (low corn), LO (low oats), and LW (low pelleted wheat middlings). Horses received an all-forage diet (2 wk; d -14 to d -1) before the treatment diets (2 wk; d 1 to 14). Starch was introduced gradually so that …

Tmem184b Promotes Axon Degeneration And Neuromuscular Junction Maintenance, Martha R.C. Bhattacharya, Stefanie Geisler, Sara K. Pittman, Ryan A. Doan, Conrad C. Weihl, Jeffrey Milbrandt, Aaron Diantonio

Open Access Publications

UNLABELLED: Complex nervous systems achieve proper connectivity during development and must maintain these connections throughout life. The processes of axon and synaptic maintenance and axon degeneration after injury are jointly controlled by a number of proteins within neurons, including ubiquitin ligases and mitogen activated protein kinases. However, our understanding of these molecular cascades is incomplete. Here we describe the phenotype resulting from mutation of TMEM184b, a protein identified in a screen for axon degeneration mediators. TMEM184b is highly expressed in the mouse nervous system and is found in recycling endosomes in neuronal cell bodies and axons. Disruption of TMEM184b expression …

Tgf-Β Neutralization Enhances Angii-Induced Aortic Rupture And Aneurysm In Both Thoracic And Abdominal Regions, Xiaofeng Chen, Debra L. Rateri, Deborah A. Howatt, Anju Balakrishnan, Jessica J. Moorleghen, Lisa A. Cassis, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

AngII and TGF-β interact in development of thoracic and abdominal aortic diseases, although there are many facets of this interaction that have not been clearly defined. The aim of the present study was to determine the effects of TGF-β neutralization on AngII induced-aortic pathologies. Male C57BL/6J mice were administered with either a rabbit or mouse TGF-β neutralizing antibody and then infused with AngII. The rabbit TGF-β antibody modestly reduced serum TGF-β concentrations, with no significant enhancements to AngII-induced aneurysm or rupture. Administration of this rabbit TGF-β antibody in mice led to high serum titers against rabbit IgG that may have …

Aphid Performance Changes With Plant Defense Mediated By Cucumber Mosaic Virus Titer, Xiaobin Shi, Yang Gao, Shuo Yan, Xin Tang, Xuguo Zhou, Deyong Zhang, Yong Liu

Entomology Faculty Publications

Background: Cucumber mosaic virus (CMV) causes appreciable losses in vegetables, ornamentals and agricultural crops. The green peach aphid, Myzus persicae Sulzer (Aphididae) is one of the most efficient vectors for CMV. The transmission ecology of aphid-vectored CMV has been well investigated. However, the detailed description of the dynamic change in the plant-CMV-aphid interaction associated with plant defense and virus epidemics is not well known.

Results: In this report, we investigated the relationship of virus titer with plant defense of salicylic acid (SA) and jasmonic acid (JA) during the different infection time and their interaction with aphids in CMV-infected tobacco plants. …