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Intestinal Stem Cells To Advance Drug Development, Precision, And Regenerative Medicine: A Paradigm Shift In Translational Research, Jonathan P. Mochel, Albert E. Jergens, Dawn Kingsbury, Hyun Jung Kim, Martín G. Martín, Karin Allenspach 2018 Iowa State University

Intestinal Stem Cells To Advance Drug Development, Precision, And Regenerative Medicine: A Paradigm Shift In Translational Research, Jonathan P. Mochel, Albert E. Jergens, Dawn Kingsbury, Hyun Jung Kim, Martín G. Martín, Karin Allenspach

Biomedical Sciences Publications

Recent advances in our understanding of the intestinal stem cell niche and the role of key signaling pathways on cell growth and maintenance have allowed the development of fully differentiated epithelial cells in 3D organoids. Stem cell-derived organoids carry significant levels of proteins that are natively expressed in the gut and have important roles in drug transport and metabolism. They are, therefore, particularly relevant to study the gastrointestinal (GI) absorption of oral medications. In addition, organoids have the potential to serve as a robust preclinical model for demonstrating the effectiveness of new drugs more rapidly, with more certainty, and at ...


The Pul37 Tegument Protein Guides Alphaherpesvirus Retrograde Axonal Transport To Promote Neuroinvasion, Alexsia L. Richards, Patricia J. Sollars, Jared D. Pitts, Austin M. Stults, Ekaterina E. Heldwein, Gary E. Pickard, Gregory A. Smith 2017 The Whitehead Institute for Biomedical Research

The Pul37 Tegument Protein Guides Alphaherpesvirus Retrograde Axonal Transport To Promote Neuroinvasion, Alexsia L. Richards, Patricia J. Sollars, Jared D. Pitts, Austin M. Stults, Ekaterina E. Heldwein, Gary E. Pickard, Gregory A. Smith

Papers in Veterinary and Biomedical Science

A hallmark property of the neurotropic alpha-herpesvirinae is the dissemination of infection to sensory and autonomic ganglia of the peripheral nervous system following an initial exposure at mucosal surfaces. The peripheral ganglia serve as the latent virus reservoir and the source of recurrent infections such as cold sores (herpes simplex virus type I) and shingles (varicella zoster virus). However, the means by which these viruses routinely invade the nervous system is not fully understood. We report that an internal virion component, the pUL37 tegument protein, has a surface region that is an essential neuroinvasion effector. Mutation of this region rendered ...


A Mutator Phenotype Promoting The Emergence Of Spontaneous Oxidative Stress-Resistant Mutants In Campylobacter Jejuni, Lei Dai, Orhan Sahin, Yizhi Tang, Qijing Zhang 2017 Iowa State University

A Mutator Phenotype Promoting The Emergence Of Spontaneous Oxidative Stress-Resistant Mutants In Campylobacter Jejuni, Lei Dai, Orhan Sahin, Yizhi Tang, Qijing Zhang

Veterinary Microbiology and Preventive Medicine Publications

Campylobacter jejuni is a leading cause of foodborne illnesses worldwide. As a microaerophilic organism, C. jejuni must be able to defend against oxidative stress encountered both in the host and in the environment. How Campylobacter utilizes a mutation-based mechanism for adaptation to oxidative stress is still unknown. Here we present a previously undescribed phenotypic and genetic mechanism that promotes the emergence of oxidative stress resistant mutants. Specifically, we showed that a naturally occurring mutator phenotype, resulting from a loss of function mutation in the DNA repair enzyme MutY, increased oxidative stress resistance (OXR) in C. jejuni. We further demonstrated ...


Effect Of Endophyte-Infected Tall Fescue Toxins On Growth Performance And The Microbial Community In The Rumen And Feces In Pregnant Ewes, Saleh Alrashedi 2017 University of Arkansas, Fayetteville

Effect Of Endophyte-Infected Tall Fescue Toxins On Growth Performance And The Microbial Community In The Rumen And Feces In Pregnant Ewes, Saleh Alrashedi

Theses and Dissertations

Fifty pregnant Katahdin ewes grazed pastures with high (HE) and moderate (MI) levels of Neotyphodium coenophialum-infected tall fescue between February 1 and May 24 to determine the impacts of tall fescue toxins on body weight (BW), body condition scores, FAMACHA scores, fecal egg counts (FEC), and serum Cu, Zn, prolactin, and non-esterified fatty acids (NEFA). Within those 50 ewes, 15 were selected randomly for fecal and rumen sampling to assess the impacts of HE and MI on the microbiome community. Total bacterial DNA was extracted from rumen and fecal samples, and alpha and beta diversities were used to relate microbiome ...


Effectiveness Of Composting As A Biosecure Disposal Method For Porcine Epidemic Diarrhea Virus (Pedv)-Infected Pig Carcasses, Sarah Vitosh-Sillman, John Dustin Loy, Bruce Brodersen, Clayton Kelling, Kent M. Eskridge, Amy Millmier Schmidt 2017 University of Nebraska-Lincoln

Effectiveness Of Composting As A Biosecure Disposal Method For Porcine Epidemic Diarrhea Virus (Pedv)-Infected Pig Carcasses, Sarah Vitosh-Sillman, John Dustin Loy, Bruce Brodersen, Clayton Kelling, Kent M. Eskridge, Amy Millmier Schmidt

Papers in Veterinary and Biomedical Science

Porcine epidemic diarrhea virus (PEDV) is an enteric disease of swine that has emerged as a worldwide threat to swine herd health and production. Substantial research has been conducted to assess viability of the virus on surfaces of vehicles and equipment, in feed and water, and on production building surfaces, but little is known about the persistence in PEDV-infected carcasses and effective disposal methods thereof. This study was conducted to quantify the persistence of PEDV RNA via quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) at various time-temperature combinations and in infected piglet carcasses subjected to composting. Although this method ...


A Multilayered Control Of The Human Survival Motor Neuron Gene Expression By Alu Elements, Eric W. Ottesen, Joonbae Seo, Natalia N. Singh, Ravindra N. Singh 2017 Iowa State University

A Multilayered Control Of The Human Survival Motor Neuron Gene Expression By Alu Elements, Eric W. Ottesen, Joonbae Seo, Natalia N. Singh, Ravindra N. Singh

Biomedical Sciences Publications

Humans carry two nearly identical copies of Survival Motor Neuron gene: SMN1 and SMN2. Mutations or deletions of SMN1, which codes for SMN, cause spinal muscular atrophy (SMA), a leading genetic disease associated with infant mortality. Aberrant expression or localization of SMN has been also implicated in other pathological conditions, including male infertility, inclusion body myositis, amyotrophic lateral sclerosis and osteoarthritis. SMN2 fails to compensate for the loss of SMN1 due to skipping of exon 7, leading to the production of SMNΔ7, an unstable protein. In addition, SMNΔ7 is less functional due to the lack of a critical C-terminus of ...


Equine Arteritis Virus Elicits A Mucosal Antibody Response In The Reproductive Tract Of Persistently Infected Stallions, Mariano Carossino, Bettina Wagner, Alan T. Loynachan, R. Frank Cook, Igor F. Canisso, Lakshman Chelvarajan, Casey L. Edwards, Bora Nam, John F. Timoney, Peter J. Timoney, Udeni B. R. Balasuriya 2017 University of Kentucky

Equine Arteritis Virus Elicits A Mucosal Antibody Response In The Reproductive Tract Of Persistently Infected Stallions, Mariano Carossino, Bettina Wagner, Alan T. Loynachan, R. Frank Cook, Igor F. Canisso, Lakshman Chelvarajan, Casey L. Edwards, Bora Nam, John F. Timoney, Peter J. Timoney, Udeni B. R. Balasuriya

Gluck Equine Research Center Faculty Publications

Equine arteritis virus (EAV) has the ability to establish persistent infection in the reproductive tract of the stallion (carrier) and is continuously shed in its semen. We have recently demonstrated that EAV persists within stromal cells and a subset of lymphocytes in the stallion accessory sex glands in the presence of a significant local inflammatory response. In the present study, we demonstrated that EAV elicits a mucosal antibody response in the reproductive tract during persistent infection with homing of plasma cells into accessory sex glands. The EAV-specific immunoglobulin isotypes in seminal plasma included IgA, IgG1, IgG3/5, and IgG4/7 ...


Cross-Reactive Immunity To Porcine Reproductive And Respiratory Syndrome Virus And Its Contribution To Protection, Ignacio Correas 2017 University of Nebraska - Lincoln

Cross-Reactive Immunity To Porcine Reproductive And Respiratory Syndrome Virus And Its Contribution To Protection, Ignacio Correas

Dissertations & Theses in Veterinary and Biomedical Science

Due to the vast geographical distribution and significant economic losses generated, porcine reproductive and respiratory syndrome virus (PRRSV) can be considered the most important swine pathogen of contemporary times. Current control and eradication strategies against PRRSV have difficulty succeeding because of their complex nature and the absence of an effective vaccine. A major obstacle for PRRSV vaccine development is the broad heterogeneity of the virus, both at the genetic and antigenic level, its rapid evolution, and an incomplete knowledge of the immune responses responsible for clearing the virus from the host. Specifically, how known correlates of protection against PRRSV—neutralizing ...


Sampling Guidelines For Oral Fluid-Based Surveys Of Group-Housed Animals, Marisa L. Rotolo, Yaxuan Sun, Chong Wang, Luis Gimenez-Lirola, David H. Baum, Phillip C. Gauger, Karen M. Harmon, Marlin Hoogland, Rodger Main, Jeffrey J. Zimmerman 2017 Iowa State University

Sampling Guidelines For Oral Fluid-Based Surveys Of Group-Housed Animals, Marisa L. Rotolo, Yaxuan Sun, Chong Wang, Luis Gimenez-Lirola, David H. Baum, Phillip C. Gauger, Karen M. Harmon, Marlin Hoogland, Rodger Main, Jeffrey J. Zimmerman

Veterinary Diagnostic and Production Animal Medicine Publications

Formulas and software for calculating sample size for surveys based on individual animal samples are readily available. However, sample size formulas are not available for oral fluids and other aggregate samples that are increasingly used in production settings. Therefore, the objective of this study was to develop sampling guidelines for oral fluid-based porcine reproductive and respiratory syndrome virus (PRRSV) surveys in commercial swine farms. Oral fluid samples were collected in 9 weekly samplings from all pens in 3 barns on one production site beginning shortly after placement of weaned pigs. Samples (n = 972) were tested by real-time reverse-transcription PCR (RT-rtPCR ...


Evaluation Of The Effect Of Serum Antibody Abundance Against Bovine Coronavirus On Bovine Coronavirus Shedding And Risk Of Respiratory Tract Disease In Beef Calves From Birth Through The First Five Weeks In A Feedlot, Aspen M. Workman, Larry A. Kuehn, Tara G. McDaneld, Michael L. Clawson, Carol G. Chitko-McKown, John Dustin Loy 2017 USDA-ARS U.S. Meat Animal Research Center

Evaluation Of The Effect Of Serum Antibody Abundance Against Bovine Coronavirus On Bovine Coronavirus Shedding And Risk Of Respiratory Tract Disease In Beef Calves From Birth Through The First Five Weeks In A Feedlot, Aspen M. Workman, Larry A. Kuehn, Tara G. Mcdaneld, Michael L. Clawson, Carol G. Chitko-Mckown, John Dustin Loy

Papers in Veterinary and Biomedical Science

Objective: To evaluate the effect of serum antibody abundance against bovine coronavirus (BCV) on BCV shedding and risk of bovine respiratory disease (BRD) in beef calves from birth through the first 5 weeks in a feedlot.

Animals: 890 natural-service crossbred beef calves from 4 research herds.

Procedures: Serial blood samples for measurement of serum anti-BCV antibody abundance by an ELISA and nasal swab specimens for detection of BCV and other viral and bacterial BRD pathogens by real-time PCR methods were collected from all calves or subsets of calves at predetermined times from birth through the first 5 weeks after feedlot ...


Hops (Humulus Lupulus L.) Bitter Acids: Modulation Of Rumen Fermentation And Potential As An Alternative Growth Promoter, Michael D. Flythe, Isabelle A. Kagan, Yuxi Wang, Nelmy Narvaez 2017 University of Kentucky

Hops (Humulus Lupulus L.) Bitter Acids: Modulation Of Rumen Fermentation And Potential As An Alternative Growth Promoter, Michael D. Flythe, Isabelle A. Kagan, Yuxi Wang, Nelmy Narvaez

Animal and Food Sciences Faculty Publications

Antibiotics can improve ruminant growth and efficiency by altering rumen fermentation via selective inhibition of microorganisms. However, antibiotic use is increasingly restricted due to concerns about the spread of antibiotic-resistance. Plant-based antimicrobials are alternatives to antibiotics in animal production. The hops plant (Humulus lupulus L.) produces a range of bioactive secondary metabolites, including antimicrobial prenylated phloroglucinols, which are commonly called alpha- and beta-acids. These latter compounds can be considered phyto-ionophores, phytochemicals with a similar antimicrobial mechanism of action to ionophore antibiotics (e.g., monensin, lasalocid). Like ionophores, the hop beta-acids inhibit rumen bacteria possessing a classical Gram-positive cell envelope. This ...


A Parapoxviral Virion Protein Inhibits Nf-Κb Signaling Early In Infection, Sushil Khatiwada, Gustavo A. Delhon, Ponnuraj Nagendraprabhu, Sabal Chaulagain, Shuhong Luo, Diego G. Diel, Eduardo F. Flores, D. L. Rock 2017 University of Illinois at Urbana-Champaign

A Parapoxviral Virion Protein Inhibits Nf-Κb Signaling Early In Infection, Sushil Khatiwada, Gustavo A. Delhon, Ponnuraj Nagendraprabhu, Sabal Chaulagain, Shuhong Luo, Diego G. Diel, Eduardo F. Flores, D. L. Rock

Papers in Veterinary and Biomedical Science

Poxviruses have evolved unique proteins and mechanisms to counteract the nuclear factor κB (NF-κB) signaling pathway, which is an essential regulatory pathway of host innate immune responses. Here, we describe a NF-κB inhibitory virion protein of orf virus (ORFV), ORFV073, which functions very early in infected cells. Infection with ORFV073 gene deletion virus (OV-IA82Δ073) led to increased accumulation of NF-κB essential modulator (NEMO), marked phosphorylation of IκB kinase (IKK) subunits IKKα and IKKβ, IκBα and NF-κB subunit p65 (NF-κB-p65), and to early nuclear translocation of NF-κB-p65 in virusinfected cells (30 min post infection). Expression of ORFV073 alone was sufficient to ...


Equine Arteritis Virus Has Specific Tropism For Stromal Cells And Cd8+ T And Cd21+ B Lymphocytes But Not For Glandular Epithelium At The Primary Site Of Persistent Infection In The Stallion Reproductive Tract, Mariano Carossino, Alan T. Loynachan, Igor F. Canisso, Richard Frank Cook, Juliana Roberta Campos, Bora Nam, Yun Young Go, Edward L. Squires, Mats H. T. Troedsson, Thomas W. Swerczek, Fabio Del Piero, Ernest F. Bailey, Peter J. Timoney, Udeni B. R. Balasuriya 2017 University of Kentucky

Equine Arteritis Virus Has Specific Tropism For Stromal Cells And Cd8+ T And Cd21+ B Lymphocytes But Not For Glandular Epithelium At The Primary Site Of Persistent Infection In The Stallion Reproductive Tract, Mariano Carossino, Alan T. Loynachan, Igor F. Canisso, Richard Frank Cook, Juliana Roberta Campos, Bora Nam, Yun Young Go, Edward L. Squires, Mats H. T. Troedsson, Thomas W. Swerczek, Fabio Del Piero, Ernest F. Bailey, Peter J. Timoney, Udeni B. R. Balasuriya

Veterinary Science Faculty Publications

Equine arteritis virus (EAV) has a global impact on the equine industry as the causative agent of equine viral arteritis (EVA), a respiratory, systemic, and reproductive disease of equids. A distinctive feature of EAV infection is that it establishes long-term persistent infection in 10 to 70% of infected stallions (carriers). In these stallions, EAV is detectable only in the reproductive tract, and viral persistence occurs despite the presence of high serum neutralizing antibody titers. Carrier stallions constitute the natural reservoir of the virus as they continuously shed EAV in their semen. Although the accessory sex glands have been implicated as ...


Comparison Of Humoral And T-Cell-Mediated Immune Responses To A Single Dose Of Bovela® Live Double Deleted Bvdv Vaccine Or To A Field Bvdv Strain, Ratree Platt, Lyle Kesl, Christian Guidarini, Chong Wang, James A. Roth 2017 Iowa State University

Comparison Of Humoral And T-Cell-Mediated Immune Responses To A Single Dose Of Bovela® Live Double Deleted Bvdv Vaccine Or To A Field Bvdv Strain, Ratree Platt, Lyle Kesl, Christian Guidarini, Chong Wang, James A. Roth

Chong Wang

The objective of this study was to determine and compare the humoral and cellular immune responses of calves exposed to a single dose of Bovela® bovine viral diarrhea virus (BVDV) live double deleted vaccine or a field strain virus (FSV) of BVDV type 2 (strain 890). Thirty seronegative, colostrum-deprived 5 month-old Holstein steer calves that tested negative for persistent BVDV by ear notch immunohistochemistry and seronegative to BVDV types 1 and 2 were used. Calves were screened by multi-parameter flow cytometry (MP-FCM) 1 week before vaccination to ensure that they were negative for T cell responses to the BVDV types ...


Key Role Of Capsular Polysaccharide In The Induction Of Systemic Infection And Abortion By Hypervirulent Campylobacter Jejuni, Orhan Sahin, Samantha A. Terhorst, Eric R. Burrough, Zhangqi Shen, Zuowei Wu, Lei Dai, Yizhi Tang, Paul J. Plummer, Ju Ji, Michael J. Yaeger, Qijing Zhang 2017 Iowa State University

Key Role Of Capsular Polysaccharide In The Induction Of Systemic Infection And Abortion By Hypervirulent Campylobacter Jejuni, Orhan Sahin, Samantha A. Terhorst, Eric R. Burrough, Zhangqi Shen, Zuowei Wu, Lei Dai, Yizhi Tang, Paul J. Plummer, Ju Ji, Michael J. Yaeger, Qijing Zhang

Veterinary Diagnostic and Production Animal Medicine Publications

Campylobacter jejuni is a zoonotic pathogen, and a hypervirulent clone, named clone SA, has recently emerged as the predominant cause of ovine abortion in the United States. To induce abortion, orally ingested Campylobacter must translocate across the intestinal epithelium, spread systemically in the circulation, and reach the fetoplacental tissue. Bacterial factors involved in these steps are not well understood. C. jejuni is known to produce capsular polysaccharide (CPS), but the specific role that CPS plays in systemic infection and particularly abortion in animals remains to be determined. In this study, we evaluated the role of CPS in bacteremia using a ...


Comparison Of Humoral And T-Cell-Mediated Immune Responses To A Single Dose Of Bovela® Live Double Deleted Bvdv Vaccine Or To A Field Bvdv Strain, Ratree Platt, Lyle Kesl, Christian Guidarini, Chong Wang, James A. Roth 2017 Iowa State University

Comparison Of Humoral And T-Cell-Mediated Immune Responses To A Single Dose Of Bovela® Live Double Deleted Bvdv Vaccine Or To A Field Bvdv Strain, Ratree Platt, Lyle Kesl, Christian Guidarini, Chong Wang, James A. Roth

Veterinary Microbiology and Preventive Medicine Publications

The objective of this study was to determine and compare the humoral and cellular immune responses of calves exposed to a single dose of Bovela® bovine viral diarrhea virus (BVDV) live double deleted vaccine or a field strain virus (FSV) of BVDV type 2 (strain 890). Thirty seronegative, colostrum-deprived 5 month-old Holstein steer calves that tested negative for persistent BVDV by ear notch immunohistochemistry and seronegative to BVDV types 1 and 2 were used. Calves were screened by multi-parameter flow cytometry (MP-FCM) 1 week before vaccination to ensure that they were negative for T cell responses to the BVDV types ...


Rnaseq Reveals Complex Response Of Campylobacter Jejuni To Ovine Bile And In Vivo Gallbladder Environment, Amanda J. Kreuder, Jennifer A. Schleining, Michael Yaeger, Qijing Zhang, Paul J. Plummer 2017 Iowa State University

Rnaseq Reveals Complex Response Of Campylobacter Jejuni To Ovine Bile And In Vivo Gallbladder Environment, Amanda J. Kreuder, Jennifer A. Schleining, Michael Yaeger, Qijing Zhang, Paul J. Plummer

Veterinary Diagnostic and Production Animal Medicine Publications

Colonization of the gallbladder by enteric pathogens such as Salmonella typhi, Listeria monocytogenes, and Campylobacter jejuni is thought to play a key role in transmission and persistence of these important zoonotic agents; however, little is known about the molecular mechanisms that allow for bacterial survival within this harsh environment. Recently, a highly virulent C. jejuni sheep abortion (SA) clone represented by the clinical isolate IA3902 has emerged as the dominant cause for sheep abortion in the United States. Previous studies have indicated that the C. jejuni clone SA can frequently be isolated from the gallbladders of otherwise healthy sheep, suggesting ...


Evaluation Of Escherichia Coli Outer Membrane Protein Etsc As A Candidate Antigen For Vaccine Against Avian Pathogenic E. Coli Infections In Chickens, David Couri 2017 Iowa State University

Evaluation Of Escherichia Coli Outer Membrane Protein Etsc As A Candidate Antigen For Vaccine Against Avian Pathogenic E. Coli Infections In Chickens, David Couri

Symposium on Undergraduate Research and Creative Expression

With the average American consuming 26 chickens per year, poultry is in high demand. Avian related infectious disease is rising and bacteria pose serious concerns for the health of livestock and possess zoonotic potential. The goal of the study is to evaluate surface protein EtsC highly prevalent among Avian Pathogenic E. coli (APEC), as a vaccine antigen candidate against these pathogens in chickens. The objective of this study is to determine antibody response in chickens vaccinated with the EtsC recombinant antigen. Eighteen 4 day-old White Leghorns (N=9/group) were subcutaneously vaccinated twice at two-week interval with PBS (control) or ...


Evaluate Broad Protection Of The Escherichia Coli Outer Membrane Protein (Omp) A Against Avian Pathogenic E. Coli Infections In Chickens, Caroline Treadwell 2017 Iowa State University

Evaluate Broad Protection Of The Escherichia Coli Outer Membrane Protein (Omp) A Against Avian Pathogenic E. Coli Infections In Chickens, Caroline Treadwell

Symposium on Undergraduate Research and Creative Expression

Avian Pathogenic E. coli (APEC) significantly impacts the poultry industry by causing the disease colibacillosis in chickens. In this research study, a vaccine containing Outer membrane protein A (OmpA), prevalent among APEC, was evaluated for its broad potential protectivity against APEC. The objectives of our study are to 1) evaluate whether an OmpA vaccine would stimulate an antibody response in chickens and 2) show in vitro broad protection against bacteria. At 4 days-old, White Leghorn chickens (9/group) were vaccinated subcutaneously twice at two week-intervals with either PBS (control) or 50 μg OmpA in CpG adjuvant. On day 33 of ...


Exogenous Lactobacilli Mitigate Microbial Changes Associated With Grain Fermentation (Corn, Oats, And Wheat) By Equine Fecal Microflora Ex Vivo, Brittany E. Harlow, Laurie M. Lawrence, Patricia A. Harris, Glen E. Aiken, Michael D. Flythe 2017 University of Kentucky

Exogenous Lactobacilli Mitigate Microbial Changes Associated With Grain Fermentation (Corn, Oats, And Wheat) By Equine Fecal Microflora Ex Vivo, Brittany E. Harlow, Laurie M. Lawrence, Patricia A. Harris, Glen E. Aiken, Michael D. Flythe

Animal and Food Sciences Faculty Publications

Cereal grains are often included in equine diets. When starch intake exceeds foregut digestion starch will reach the hindgut, impacting microbial ecology. Probiotics (e.g., lactobacilli) are reported to mitigate GI dysbioses in other species. This study was conducted to determine the effect of exogenous lactobacilli on pH and the growth of amylolytic and lactate-utilizing bacteria. Feces were collected from 3 mature geldings fed grass hay with access to pasture. Fecal microbes were harvested by differential centrifugation, washed, and re-suspended in anaerobic media containing ground corn, wheat, or oats at 1.6% (w/v) starch and one of five treatments ...


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