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Zika Virus Infection Causes Temporary Paralysis In Adult Mice With Motor Neuron Synaptic Retraction And Evidence For Proximal Peripheral Neuropathy, John D. Morrey, Alexandre L. R. Oliveira, Hong Wang, Katherine Zukor, Mateus Vidigal De Castro, Venkatraman Siddharthan Dec 2019

Zika Virus Infection Causes Temporary Paralysis In Adult Mice With Motor Neuron Synaptic Retraction And Evidence For Proximal Peripheral Neuropathy, John D. Morrey, Alexandre L. R. Oliveira, Hong Wang, Katherine Zukor, Mateus Vidigal De Castro, Venkatraman Siddharthan

Animal, Dairy, and Veterinary Science Faculty Publications

Clinical evidence is mounting that Zika virus can contribute to Guillain-Barré syndrome which causes temporary paralysis, yet the mechanism is unknown. We investigated the mechanism of temporary acute flaccid paralysis caused by Zika virus infection in aged interferon αβ-receptor knockout mice used for their susceptibility to infection. Twenty-five to thirty-five percent of mice infected subcutaneously with Zika virus developed motor deficits including acute flaccid paralysis that peaked 8-10 days after viral challenge. These mice recovered within a week. Despite Zika virus infection in the spinal cord, motor neurons were not destroyed. We examined ultrastructures of motor neurons and synapses by …


Docosahexaenoic Acid Consumption Impedes Early Interferon- And Chemokine-Related Gene Expression While Suppressing Silica-Triggered Flaring Of Murine Lupus, Abby D. Benninghoff, Melissa A. Bates, Preeti S. Chauhan, Kathryn A. Wierenga, Kristen N. Gilley, Andrij Holian, Jack R. Harkema, James J. Pestka Dec 2019

Docosahexaenoic Acid Consumption Impedes Early Interferon- And Chemokine-Related Gene Expression While Suppressing Silica-Triggered Flaring Of Murine Lupus, Abby D. Benninghoff, Melissa A. Bates, Preeti S. Chauhan, Kathryn A. Wierenga, Kristen N. Gilley, Andrij Holian, Jack R. Harkema, James J. Pestka

Animal, Dairy, and Veterinary Science Faculty Publications

Exposure of lupus-prone female NZBWF1 mice to respirable crystalline silica (cSiO2), a known human autoimmune trigger, initiates loss of tolerance, rapid progression of autoimmunity, and early onset of glomerulonephritis. We have previously demonstrated that dietary supplementation with the ω-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) suppresses autoimmune pathogenesis and nephritis in this unique model of lupus flaring. In this report, we utilized tissues from prior studies to test the hypothesis that DHA consumption interferes with upregulation of critical genes associated with cSiO2-triggered murine lupus. A NanoString nCounter platform targeting 770 immune-related genes was used to assess …


Vascular Leak And Hypercytokinemia Associated With Severe Fever With Thrombocytopenia Syndrome Virus Infection In Mice, Jonna B. Westover, Brady T. Hickerson, Arnaud J. Van Wettere, Brett L. Hurst, Jacqueline P. Kurz, Ashley Dagley, Petra Wülfroth, Takashi Komeno, Yousuke Furuta, Thomas Steiner, Brian B. Gowen Sep 2019

Vascular Leak And Hypercytokinemia Associated With Severe Fever With Thrombocytopenia Syndrome Virus Infection In Mice, Jonna B. Westover, Brady T. Hickerson, Arnaud J. Van Wettere, Brett L. Hurst, Jacqueline P. Kurz, Ashley Dagley, Petra Wülfroth, Takashi Komeno, Yousuke Furuta, Thomas Steiner, Brian B. Gowen

Animal, Dairy, and Veterinary Science Faculty Publications

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever (VHF) endemic to China, South Korea, Japan, and Vietnam. Here we characterize the pathogenesis and natural history of disease in IFNAR-/- mice challenged with the HB29 strain of SFTS virus (SFTSV) and demonstrate hallmark features of VHF such as vascular leak and high concentrations of proinflammatory cytokines in blood and tissues. Treatment with FX06, a natural plasmin digest product of fibrin in clinical development as a treatment for vascular leak, reduced vascular permeability associated with SFTSV infection but did not significantly improve survival outcome. Further studies are …


Function And Transcriptional Regulation Of Bovine Torc2 Gene In Adipocytes: Roles Of C/Ebpγ, Xbp1, Insm1 And Znf263, Rajwali Khan, Sayed Haidar Abbas Raza, Zainaguli Junjvlieke, Wang Xiaoyu, Matthew D. Garcia, Ibrahim Elsaeid Elnour, Wang Hongbao, Zan Linsen Sep 2019

Function And Transcriptional Regulation Of Bovine Torc2 Gene In Adipocytes: Roles Of C/Ebpγ, Xbp1, Insm1 And Znf263, Rajwali Khan, Sayed Haidar Abbas Raza, Zainaguli Junjvlieke, Wang Xiaoyu, Matthew D. Garcia, Ibrahim Elsaeid Elnour, Wang Hongbao, Zan Linsen

Animal, Dairy, and Veterinary Science Faculty Publications

The TORC2 gene is a member of the transducer of the regulated cyclic adenosine monophosphate (cAMP) response element binding protein gene family, which plays a key role in metabolism and adipogenesis. In the present study, we confirmed the role of TORC2 in bovine preadipocyte proliferation through cell cycle staining flow cytometry, cell counting assay, 5-ethynyl-20 -deoxyuridine staining (EdU), and mRNA and protein expression analysis of proliferation-related marker genes. In addition, Oil red O staining analysis, immunofluorescence of adiponectin, mRNA and protein level expression of lipid related marker genes confirmed the role of TORC2 in the regulation of bovine adipocyte differentiation. …


Basal Diet Determined Long-Term Composition Of The Gut Microbiome And Mouse Phenotype To A Greater Extent Than Fecal Microbiome Transfer From Lean Or Obese Human Donors, Daphne Michelle Rodriguez Jimenez, Abby D. Benninghoff, Niklas D.J. Aardema, Sumira Phatak, Korry J. Hintze Jul 2019

Basal Diet Determined Long-Term Composition Of The Gut Microbiome And Mouse Phenotype To A Greater Extent Than Fecal Microbiome Transfer From Lean Or Obese Human Donors, Daphne Michelle Rodriguez Jimenez, Abby D. Benninghoff, Niklas D.J. Aardema, Sumira Phatak, Korry J. Hintze

Animal, Dairy, and Veterinary Science Faculty Publications

The Western dietary pattern can alter the gut microbiome and cause obesity and metabolic disorders. To examine the interactions between diet, the microbiome, and obesity, we transplanted gut microbiota from lean or obese human donors into mice fed one of three diets for 22 weeks: (1) a control AIN93G diet; (2) the total Western diet (TWD), which mimics the American diet; or (3) a 45% high-fat diet-induced obesity (DIO) diet. We hypothesized that a fecal microbiome transfer (FMT) from obese donors would lead to an obese phenotype and aberrant glucose metabolism in recipient mice that would be exacerbated by consumption …


Zika Virus Associated Pathology And Antigen Presence In The Testicle In The Absence Of Sexual Transmission During Subacute To Chronic Infection In A Mouse Model, Chad S. Clancy, Arnaud J. Van Wettere, John D. Morrey, Justin G. Julander Jun 2019

Zika Virus Associated Pathology And Antigen Presence In The Testicle In The Absence Of Sexual Transmission During Subacute To Chronic Infection In A Mouse Model, Chad S. Clancy, Arnaud J. Van Wettere, John D. Morrey, Justin G. Julander

Animal, Dairy, and Veterinary Science Faculty Publications

Zika virus (ZIKV) is an arboviral infection that has been shown to be sexually transmitted. The study outlined herein aims to determine if accessory sex glands and epididymal epithelial cells are sources of viral persistence in subacute and chronic ZIKV infection, and if infection of these organs is important in sexual transmission during long-term (chronic) infection. Male interferon type I receptor knockout (Ifnar−/−) mice were challenged with ZIKV and reproductive tissues were harvested 14 and 35 days post infection (DPI) for inoculation studies and 14, 35 and 70 DPI for histopathology. Artificial insemination fluid derived from epididymal …


Incomplete Urethral Duplication Associated With A Dermoid Cyst Within A Vascular Hamartoma In A Female Dog, Chad S. Clancy, Gordon A. Hullinger, Arnaud J. Van Wettere May 2019

Incomplete Urethral Duplication Associated With A Dermoid Cyst Within A Vascular Hamartoma In A Female Dog, Chad S. Clancy, Gordon A. Hullinger, Arnaud J. Van Wettere

Animal, Dairy, and Veterinary Science Faculty Publications

A seven-year-old spayed female Labrador retriever presented for necropsy following an acute history of thrombocytopenia, anemia, leukocytosis and abdominal effusion. A 2 × 3 × 10 cm, cylindrical to tubular, mottled red-to-tan mass extended from the caudal pelvic cavity caudally and ventrally under the dermis along the caudal aspect of the left pelvic limb adjacent to the semimembranosus and semitendinosus musculature. Histologic examination of the mass revealed a singular central lumen lined by urothelium that multifocally transitioned into non-keratinizing, stratified squamous epithelium associated with few hair follicles and sweat glands. The lumen was surrounded by a dense collagenous stroma containing …


Lack Of Selective Resistance Of Influenza A Virus In Presence Of Host-Targeted Antiviral, Uv-4b, Kelly L. Warfield, Kaitlyn R. Schaaf, Lisa Evans Dewald, Kevin B. Spurgers, Wei Wang, Eric Stavale, Michelle Mendenhall, Meghan H. Shilts, Timothy B. Stockwell, Dale L. Barnard, Urban Ramstedt, Suman R. Das May 2019

Lack Of Selective Resistance Of Influenza A Virus In Presence Of Host-Targeted Antiviral, Uv-4b, Kelly L. Warfield, Kaitlyn R. Schaaf, Lisa Evans Dewald, Kevin B. Spurgers, Wei Wang, Eric Stavale, Michelle Mendenhall, Meghan H. Shilts, Timothy B. Stockwell, Dale L. Barnard, Urban Ramstedt, Suman R. Das

Animal, Dairy, and Veterinary Science Faculty Publications

Development of antiviral drug resistance is a continuous concern for viruses with high mutation rates such as influenza. The use of antiviral drugs targeting host proteins required for viral replication is less likely to result in the selection of resistant viruses than treating with direct-acting antivirals. The iminosugar UV-4B is a host-targeted glucomimetic that inhibits endoplasmic reticulum α-glucosidase I and II enzymes resulting in improper glycosylation and misfolding of viral glycoproteins. UV-4B has broad-spectrum antiviral activity against diverse viruses including dengue and influenza. To examine the ability of influenza virus to develop resistance against UV-4B, mouse-adapted influenza virus was passaged …


Genome To Phenome: Improving Animal Health, Production, And Well-Being – A New Usda Blueprint For Animal Genome Research 2018–2027, Caird Rexroad, Jeffrey Vallet, Lakshmi Kumar Matukumalli, James Reecy, Derek Bickhart, Harvey Blackburn, Mark Boggess, Hans Cheng, Archie Clutter, Noelle Cockett, Catherine Ernst, Janet E. Fulton, John Liu, Joan Lunney, Holly Neibergs, Et Al. May 2019

Genome To Phenome: Improving Animal Health, Production, And Well-Being – A New Usda Blueprint For Animal Genome Research 2018–2027, Caird Rexroad, Jeffrey Vallet, Lakshmi Kumar Matukumalli, James Reecy, Derek Bickhart, Harvey Blackburn, Mark Boggess, Hans Cheng, Archie Clutter, Noelle Cockett, Catherine Ernst, Janet E. Fulton, John Liu, Joan Lunney, Holly Neibergs, Et Al.

Animal, Dairy, and Veterinary Science Faculty Publications

In 2008, a consortium led by the Agricultural Research Service (ARS) and the National Institute for Food and Agriculture (NIFA) published the “Blueprint for USDA Efforts in Agricultural Animal Genomics 2008–2017,” which served as a guiding document for research and funding in animal genomics. In the decade that followed, many of the goals set forth in the blueprint were accomplished. However, several other goals require further research. In addition, new topics not covered in the original blueprint, which are the result of emerging technologies, require exploration. To develop a new, updated blueprint, ARS and NIFA, along with scientists in the …


Altered Gene Response To Aflatoxin B1 In The Spleens Of Susceptible And Resistant Turkeys, Kent M. Reed, Kristelle M. Mendoza, Roger A. Coulombe Jr. Apr 2019

Altered Gene Response To Aflatoxin B1 In The Spleens Of Susceptible And Resistant Turkeys, Kent M. Reed, Kristelle M. Mendoza, Roger A. Coulombe Jr.

Animal, Dairy, and Veterinary Science Faculty Publications

Susceptibility and/or resistance to aflatoxin B1 (AFB1) is a threshold trait governed principally by glutathione S transferase (GST)-mediated detoxification. In poultry, domesticated turkeys are highly sensitive to AFB1, most likely due to dysfunction in hepatic GSTs. In contrast, wild turkeys are comparatively resistant to aflatoxicosis due to the presence of functional hepatic GSTAs and other possible physiological and immunological interactions. The underlying genetic basis for the disparate GST function in turkeys is unknown as are the broader molecular interactions that control the systemic response. This study quantifies the effects of dietary AFB1 on gene …


Efficacy Of A Ml336 Derivative Against Venezuelan And Eastern Equine Encephalitis Viruses, Colleen B. Jonsson, Xufeng Cao, Jasper Lee, Jon D. Gabbard, Yong-Kyu Chu, Elizabeth A. Fitzpatrick, Justin G. Julander, Dong-Hoon Chung, Jennifer Stabenow, Jennifer E. Golden Apr 2019

Efficacy Of A Ml336 Derivative Against Venezuelan And Eastern Equine Encephalitis Viruses, Colleen B. Jonsson, Xufeng Cao, Jasper Lee, Jon D. Gabbard, Yong-Kyu Chu, Elizabeth A. Fitzpatrick, Justin G. Julander, Dong-Hoon Chung, Jennifer Stabenow, Jennifer E. Golden

Animal, Dairy, and Veterinary Science Faculty Publications

Currently, there are no licensed human vaccines or antivirals for treatment of or prevention from infection with encephalitic alphaviruses. Because epidemics are sporadic and unpredictable, and endemic disease is common but rarely diagnosed, it is difficult to identify all populations requiring vaccination; thus, an effective post-exposure treatment method is needed to interrupt ongoing outbreaks. To address this public health need, we have continued development of ML336 to deliver a molecule with prophylactic and therapeutic potential that could be relevant for use in natural epidemics or deliberate release scenario for Venezuelan equine encephalitis virus (VEEV). We report findings from in vitro …


Mapping Of Dynamic Transcriptome Changes Associated With Silica-Triggered Autoimmune Pathogenesis In The Lupus-Prone Nzbwf1 Mouse, Melissa A. Bates, Abby D. Benninghoff, Kristen N. Gilley, Andrij Holian, Jack R. Harkema, James J. Pestka Mar 2019

Mapping Of Dynamic Transcriptome Changes Associated With Silica-Triggered Autoimmune Pathogenesis In The Lupus-Prone Nzbwf1 Mouse, Melissa A. Bates, Abby D. Benninghoff, Kristen N. Gilley, Andrij Holian, Jack R. Harkema, James J. Pestka

Animal, Dairy, and Veterinary Science Faculty Publications

Crystalline silica (cSiO2) is a widely recognized environmental trigger of autoimmune disease. In the lupus-prone female NZBWF1 mouse, airway exposure to cSiO2 triggers pulmonary ectopic lymphoid neogenesis, systemic autoantibody elevation, and glomerulonephritis. Here we tested the hypothesis that upregulation of adaptive immune function genes in the lung precedes cSiO2-triggering of autoimmune disease in this model. The study include three groups of mice, as follows: (1) necropsied 1 d after a single intranasal instillation of 1 mg cSiO2 or vehicle, (2) necropsied 1 d after four weekly single instillations of 1 mg cSiO2 or …


Generation Of H7n9-Specific Human Polyclonal Antibodies From A Transchromosomic Goat (Caprine) System, Hua Wu, Zhiqiang Fan, Michelle Brandsrud, Qinggang Meng, Molly Bobbitt, Misha Regouski, Rusty Stott, Alexis Sweat, Jackelyn Crabtree, Robert J. Hogan, Ralph A. Tripp, Zhongde Wang, Irina A. Polejaeva, Eddie J. Sullivan Jan 2019

Generation Of H7n9-Specific Human Polyclonal Antibodies From A Transchromosomic Goat (Caprine) System, Hua Wu, Zhiqiang Fan, Michelle Brandsrud, Qinggang Meng, Molly Bobbitt, Misha Regouski, Rusty Stott, Alexis Sweat, Jackelyn Crabtree, Robert J. Hogan, Ralph A. Tripp, Zhongde Wang, Irina A. Polejaeva, Eddie J. Sullivan

Animal, Dairy, and Veterinary Science Faculty Publications

To address the unmet needs for human polyclonal antibodies both as therapeutics and diagnostic reagents, building upon our previously established transchromosomic (Tc) cattle platform, we report herein the development of a Tc goat system expressing human polyclonal antibodies in their sera. In the Tc goat system, a human artificial chromosome (HAC) comprising the entire human immunoglobulin (Ig) gene repertoire in the germline configuration was introduced into the genetic makeup of the domestic goat. We achieved this by transferring the HAC into goat fetal fibroblast cells followed by somatic cell nuclear transfer for Tc goat production. Gene and protein expression analyses …


Human Polyclonal Antibodies Produced From Transchromosomal Bovine Provides Prophylactic And Therapeutic Protections Against Zika Virus Infection In Stat2 Ko Syrian Hamsters, Venkatraman Siddharthan, Jinxin Miao, Arnaud J. Van Wettere, Rong Li, Hua Wu, Eddie Sullivan, Jinan Jiao, Jay W. Hooper, David Safronetz, John D. Morrey, Justin G. Julander, Zhongde Wang Jan 2019

Human Polyclonal Antibodies Produced From Transchromosomal Bovine Provides Prophylactic And Therapeutic Protections Against Zika Virus Infection In Stat2 Ko Syrian Hamsters, Venkatraman Siddharthan, Jinxin Miao, Arnaud J. Van Wettere, Rong Li, Hua Wu, Eddie Sullivan, Jinan Jiao, Jay W. Hooper, David Safronetz, John D. Morrey, Justin G. Julander, Zhongde Wang

Animal, Dairy, and Veterinary Science Faculty Publications

Zika virus (ZIKV) infection can cause severe congenital diseases, such as microcephaly, ocular defects and arthrogryposis in fetuses, and Guillain–Barré syndrome in adults. Efficacious therapeutic treatments for infected patients, as well as prophylactic treatments to prevent new infections are needed for combating ZIKV infection. Here, we report that ZIKV-specific human polyclonal antibodies (SAB-155), elicited in transchromosomal bovine (TcB), provide significant protection from infection by ZIKV in STAT2 knockout (KO) golden Syrian hamsters both prophylactically and therapeutically. These antibodies also prevent testicular lesions in this hamster model. Our data indicate that antibody-mediated immunotherapy is effective in treating ZIKV infection. Because suitable …


Differential Transcriptome Responses To Aflatoxin B1 In The Cecal Tonsil Of Susceptible And Resistant Turkeys, Kent M. Reed, Kristelle M. Mendoza, Roger A. Coulombe Jr. Jan 2019

Differential Transcriptome Responses To Aflatoxin B1 In The Cecal Tonsil Of Susceptible And Resistant Turkeys, Kent M. Reed, Kristelle M. Mendoza, Roger A. Coulombe Jr.

Animal, Dairy, and Veterinary Science Faculty Publications

The nearly-ubiquitous food and feed-borne mycotoxin aflatoxin B1 (AFB1) is carcinogenic and mutagenic, posing a food safety threat to humans and animals. One of the most susceptible animal species known and thus a good model for characterizing toxicological pathways, is the domesticated turkey (DT), a condition likely due, at least in part, to deficient hepatic AFB1-detoxifying alpha-class glutathione S-transferases (GSTAs). Conversely, wild turkeys (Eastern wild, EW) are relatively resistant to the hepatotoxic, hepatocarcinogenic and immunosuppressive effects of AFB1 owing to functional gene expression and presence of functional hepatic GSTAs. This study was designed to …


Decreased Sarcopenia In Aged Females With Young Ovary Transplants Was Preserved In Mice That Received Germ Cell-Depleted Young Ovaries, Tracy L. Habermehl, Jeffrey B. Mason Jan 2019

Decreased Sarcopenia In Aged Females With Young Ovary Transplants Was Preserved In Mice That Received Germ Cell-Depleted Young Ovaries, Tracy L. Habermehl, Jeffrey B. Mason

Animal, Dairy, and Veterinary Science Faculty Publications

Previously, transplantation of young, cycling, ovaries increased life and health span in post-reproductive female mice. The current study addressed the influence of ovarian germ cells in the improvement in health by performing transplantations of young, germ cell-depleted ovaries. The purpose of this study is to further the understanding of reproductive influences on aging health. Control mice were grouped by age. Treatment mice were age-matched and received either germ cell depleted ovaries or germ cell containing ovaries at 400 days of age. All groups underwent health span assays until sacrifice (treatment and age-matched control groups were between 680 and 700 days). …