Medicine and Health Sciences Commons^™

Loss Of Thiol Repair Systems In Human Cataractous Lenses, Min Wei, Kui-Yi Xing, Yin-Chuan Fan, Teodosio Libondi, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

PURPOSE. The purpose of this study was to investigate the thiol repair systems of thioltransferase (TTase) and thioredoxin (Trx) and oxidation-damaged proteins in human cataractous lenses.

METHODS. Cataractous lenses in humans (57–85 years of age) were classified into cortical, nuclear, mixed, mature, and hypermature cataract types by using a lens opacity classification system, and were obtained by extracapsular cataract extraction (ECCE) procedure. Cortical and nuclear cataracts were grouped by decreasing order of visual acuity into optical chart reading (R), counting fingers (CF), hand motion (HM), and light perception (LP). ECCE lens homogenate was analyzed for glutathione (GSH) level and enzyme …

Glutaredoxin 2 (Grx2) Gene Deletion Induces Early Onset Of Age-Dependent Cataracts In Mice, Hongli Wu, Yibo Yu, Larry David, Ye-Shih Ho, Marjorie . F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

Glutaredoxin 2 (Grx2) is an isozyme of glutaredoxin1 (thioltransferase) present in the mitochondria and nucleus with disulfide reductase and peroxidase activities, and it controls thiol/ disulfide balance in cells. In this study, we investigated whether Grx2 gene deletion could induce faster age-related cataract formation and elucidated the biochemical changes effected by Grx2 gene deletion that may contribute to lens opacity. Slit lamp was used to examine the lenses in Grx2 knock-out (KO) mice and age-matched wild-type (WT) mice ages 1 to 16 months. In the Grx2 null mice, the lens nuclear opacity began at 5 months, 3 months sooner than …

Glucose Significantly Enhances Enterotoxigenic Escherichia Coli Adherence To Intestinal Epithelial Cells Through Its Effects On Heat-Labile Enterotoxin Production, Prageeth Wijemanne, Rodney A. Moxley

School of Veterinary and Biomedical Sciences: Faculty Publications

The present study tested whether exposure of enterotoxigenic Escherichia coli (ETEC) to glucose at different concentrations in the media results in increased bacterial adherence to host cells through increased heat-labile enterotoxin (LT) production, thereby suggesting the effects are physiological. Porcine-origin ETEC strains grown in Casamino acid yeast extract medium containing different concentrations of glucose were washed and inoculated onto IPEC-J2 porcine intestinal epithelial cells to test for effects on adherence and host cell cAMP concentrations. Consistent with previous studies, all LT+ strains had higher ETEC adherence to IPEC-J2 cells than did LT2 strains. Adherence of the LT2 but not the …

A Rational Framework For Evaluating The Next Generation Of Vaccines Against Mycobacterium Avium Subspecies Paratuberculosis, John P. Bannantine, Murray E. Hines Ii, Luiz E. Bermudez, Adel M. Talaat, Srinand Sreevatsan, Judith R. Stabel, Yung-Fu Chang, Paul M. Coussens, Raúl G. Barletta, William C. Davis, Desmond M. Collins, Yrjö T. Gröhn, Vivek Kapur

School of Veterinary and Biomedical Sciences: Faculty Publications

Since the early 1980s, several investigations have focused on developing a vaccine against Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of Johne's disease in cattle and sheep. These studies used whole-cell inactived vaccines that have proven useful in limiting disease progression, but have not prevented infection. In contrast, modified live vaccines that invoke a Th1 type immune response, may improve protection against infection. Spurred by recent advances in the ability to create defined knockouts in MAP, several independent laboratories have developed modified live vaccine candidates by transcriptional mutation of virulence and metablolic genes in MAP. In order to accelerate …

Evaluation Of Eight Live Attenuated Vaccine Candidates For Protection Against Challenge With Virulent Mycobacterium Avium Subspecies Paratuberclosis In Mice, John Bannantine, Jamie L. Everman, Sasha J. J.Rose, Lmar Babrak, Robab Katani, Raul G. Barletta, Adel M. Talaat, Yrjö J. Gröhn, Yung-Fu Chang, Vivek Kapur, Luiz E. Bermudez

School of Veterinary and Biomedical Sciences: Faculty Publications

Johne's disease is caused by Mycobacterium avium subsp. paratuberculosis (MAP), which results in serious economic losses worldwide in farmed livestock such as cattle, sheep, and goats. To control this disease, an effective vaccine with minimal adverse effects is needed. In order to identify a live vaccine for Johne's disease, we evaluated eight attenuated mutant strains of MAP using a C57BL/6 mouse model. The persistaence of the vaccine candidates was measured at 6, 12, and 18 weeks post vaccination. Only strains 320, 321, and 329 colonized both the liver and spleens up until the 12-week time point. The remaining five mutants …

Conformationally Stabilized Hiv Envelope Immunogens, Peter Kwong, John Mascola, Gary Nabel, Richard Wyatt, Barna Dey, Ling Xu, Tongqing Zhou, Joseph Sodroski, Wen Yuan, Shi-Hua Xiang

School of Veterinary and Biomedical Sciences: Faculty Publications

Isolated immunogens including a HIV-1 gp120 polypeptide or immunogenic fragment thereof stabilized in a CD4 bound confirmation by crosslinked cysteines, and methods of their use are disclosed. The immunogens are useful, for example, for generating an immune response to HIV-1 gp120 in a Subject.

Cd8Α Dendritic Cells Drive Establishment Of Hsv-1 Latency, Kevin R. Mott, Sariah J. Allen, Mandana Zandian, Bindu Konda, Behrooz G. Sharifi, Clinton Jones, Steven L. Wechsler, Terrence Town, Homayon Ghiasi

School of Veterinary and Biomedical Sciences: Faculty Publications

It is generally accepted that CD8 T cells play the key role to maintain HSV-1 latency in trigeminal ganglia of ocularly infected mice. Yet, comparably little is known about the role of innate immunity in establishment of viral latency. In the current study, we investigated whether CD8α DCs impact HSV-1 latency by examining latency in the trigeminal ganglia (TG) of wildtype (WT) C57BL/6 versus CD8α^‒/‒ (lack functional CD8 T cells and CD8α⁺ DCs), CD8β^‒/‒ (have functional CD8α⁺ T cells and CD8α⁺ DCs), and β2m^‒/‒ (lack functional CD8 T cells but have CD8α^{+ …}

Overexpression Of Thioredoxin Binding Protein (Tbp-2) Increases Oxidation Sensitivity And Apoptosis In Human Lens Epithelial Cells, Yibo Yu, Kuiyi Xing, Rilwan Badamas, Charles A. Kuszynski, Hongli Wuand, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

Thioredoxin (Trx) is an important redox regulator with cytosolic Trx1 and mitochondrial Trx2 isozymes. Trx has multi-physiological functions in cells and its bioavailability is negatively controlled through active site binding to a specific thioredoxin binding protein (TBP-2). This paper describes the delicate balance between TBP-2 and Trx, and the effect of overexpression of TBP-2 in the human lens epithelial cells. Cells overexpressing TBP-2 (TBP-2 OE) showed a 7- fold increase of TBP-2, and a nearly 40% suppression of Trx activity but no change in Trx expression. The TBP-2 OE cells grew slower and their population decreased to 30% by day …

Evaluation Of Novel Oral Vaccine Candidates And Validation Of A Caprine Model Of Johne’S Disease, Murray E. Hines Ii, Sue E. Turnquist, Marcia R.S. Ilha, Sreekumari Rajeev, Arthur L. Jones, Lisa Whittington, John P. Bannantine, Raul G. Barletta, Yrjö T. Gröhn, Robab Katani, Adel M. Talaat, Lingling Li, Vivek Kapur

School of Veterinary and Biomedical Sciences: Faculty Publications

Johne’s disease (JD) caused by Mycobacterium avium subspecies paratuberculosis (MAP) is a major threat to the dairy industry and possibly some cases of Crohn’s disease in humans. A MAP vaccine that reduced of clinical disease and/or reduced fecal shedding would aid in the control of JD. The objectives of this study were (1) to evaluate the efficacy of 5 attenuated strains of MAP as vaccine candidates compared to a commercial control vaccine using the protocol proposed by the Johne’s Disease Integrated Program (JDIP) Animal Model Standardization Committee (AMSC), and (2) to validate the AMSC Johne’s disease go at challenge model. …

Direct Staining With Major Histocompatibility Complex Class Ii Dextramers Permits Detection Of Antigen- Specific, Autoreactive Cd4 T Cells In Situ, Chandirasegaran Massilamany, Arunakumar Gangaplara, Ting Jia, Christian Elowsky, Guobin Kang, Jean-Jack Riethoven, Qingsheng Li, You Zhou, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

We report here the utility of major histocompatibility complex (MHC) class II dextramers for in situ detection of self-reactive CD4 T cells in two target organs, the brain and heart. We optimized the conditions for in situ detection of antigen-specific CD4 T cells using brain sections obtained from SJL mice immunized with myelin proteolipid protein (PLP) 139–151; the sections were costained with IA^s/PLP 139–151 (specific) or Theiler’s murine encephalomyelitis virus (TMEV) 70–86 (control) dextramers and anti-CD4. Analysis of sections by laser scanning confocal microscope revealed detection of cells positive for PLP 139–151 but not for TMEV 70–86 dextramers …

Influence Of Iron And Aeration On Staphylococcus Aureus Growth, Metabolism, And Transcription, Nagender Ledala, Bo Zhang, Javier Seravalli, Robert Powers, Greg Somerville

School of Veterinary and Biomedical Sciences: Faculty Publications

Staphylococcus aureus is a prominent nosocomial pathogen and a major cause of biomaterial-associated infections. The success of S. aureus as a pathogen is due in part to its ability to adapt to stressful environments. As an example, the transition from residing in the nares to residing in the blood or deeper tissues is accompanied by changes in the availability of nutrients and elements such as oxygen and iron. As such, nutrients, oxygen, and iron are important determinants of virulence factor synthesis in S. aureus. In addition to influencing virulence factor synthesis, oxygen and iron are critical cofactors in enzymatic and …

Novel Gammaherpesvirus Functions 1 Encoded By Bovine Herpesvirus (Bovine Lymphotropic Virus), J. Jia, G. Delhon, E. R. Tulman, D. G. Diel, Fernando A. Osorio, X. Wen, G. F. Kutish, D. L. Rock

School of Veterinary and Biomedical Sciences: Faculty Publications

The genus Macavirus of the subfamily Gammaherpesvirinae includes viruses that infect lymphoid cells of domestic and wild ruminants and swine, causing asymptomatic latent infections in reservoir hosts. Here, we describe the genome of bovine herpesvirus 6 (BoHV-6), a

macavirus ubiquitous in healthy cattle populations. The BoHV-6 genome exhibited architecture conserved in macaviruses, including a repetitive H-DNA region and unique, 141 kilobase pair L

DNA region predicted to encode 77 genes. BoHV-6 encoded in variable genomic regions a novel complement of genes relative to other characterized macaviruses, likely contributing to distinctive aspects of BoHV-6 infection biology and host range. Most notably, …

Experimental Infection Of Pregnant Goats With Bovine Viral Diarrhea Virus (Bvdv) 1 Or 2, Thomas Passler, Kay P. Riddell, Misty A. Edmondson, Manuel F. Chamorro, John D. Neill, Bruce W. Brodersen, Heather L. Walz, Patricia K. Galik, Yijing Zhang, Paul H. Walz

School of Veterinary and Biomedical Sciences: Faculty Publications

Infections with bovine viral diarrhea virus (BVDV) of the genus pestivirus, family Flaviviridae, are not limited to cattle but occur in various artiodactyls. Persistently infected (PI) cattle are the main source of BVDV. Persistent infections also occur in heterologous hosts such as sheep and deer. BVDV infections of goats commonly result in reproductive disease, but viable PI goats are rare. Using 2 BVDV isolates, previously demonstrated to cause PI cattle and white-tailed deer, this study evaluated the outcome of experimental infection of pregnant goats. Pregnant goats (5 goats/group) were intranasally inoculated with BVDV 1b AU526 (group 1) or BVDV 2 …

Light Stimulates The Mouse Adrenal Through A Retinohypothalamic Pathway Independent Of An Effect On The Clock In The Suprachiasmatic Nucleus, Silke Kiessling, Patricia J. Sollars, Gary E. Pickard

School of Veterinary and Biomedical Sciences: Faculty Publications

The brain’s master circadian pacemaker resides within the hypothalamic suprachiasmatic nucleus (SCN). SCN clock neurons are entrained to the day/night cycle via the retinohypothalamic tract and the SCN provides temporal information to the central nervous system and to peripheral organs that function as secondary oscillators. The SCN clock-cell network is thought to be the hypothalamic link between the retina and descending autonomic circuits to peripheral organs such as the adrenal gland, thereby entraining those organs to the day/night cycle. However, there are at least three different routes or mechanisms by which retinal signals transmitted to the hypothalamus may be conveyed …

Sumoylation Differentially Regulates Sp1 To Control Cell Differentiation, Lili Gong, Wei-Ke Ji, Xiao-Hui Hu, Wen-Feng Hu, Xiang-Cheng Tang, Zhao-Xia Huang, Ling Li, Mugen Liu, Shi-Hua Xiang, Erxi Wu, Zachary Woodward, Yi-Zhi Liu, Quan Dong Nguyen, David Wan-Cheng Li

School of Veterinary and Biomedical Sciences: Faculty Publications

The mammalian small ubiquitin-like modifiers (SUMOs) are actively involved in regulating differentiation of different cell types. However, the functional differences between SUMO isoforms and their mechanisms of action remain largely unknown. Using the ocular lens as a model system, we demonstrate that different SUMOs display distinct functions in regulating differentiation of epithelial cells into fiber cells. During lens differentiation, SUMO1 and SUMO2/3 displayed different expression, localization, and targets, suggesting differential functions. Indeed, overexpression of SUMO2/3, but not SUMO1, inhibited basic (b) FGF-induced cell differentiation. In contrast, knockdown of SUMO1, but not SUMO2/3, also inhibited bFGF action. Mechanistically, specificity protein 1 …

Generation Of Calves Persistently Infected With Hobi-Like Pestivirus And Comparison Of Methods For Detection Of These Persistent Infections, F. V. Bauermann, S. M. Falkenberg, B. Vander Ley, N. Decaro, Bruce W. Brodersen, A. Harmon, B. Hessman, E. F. Flores, J. F. Ridpath

School of Veterinary and Biomedical Sciences: Faculty Publications

The identification and elimination of persistently infected (PI) cattle are the most effective measures for controlling bovine pestiviruses, including bovine viral diarrhea virus (BVDV) and the emerging HoBi-like viruses. Here, colostrum-deprived calves persistently infected with HoBi-like pestivirus (HoBi-like PI calves) were generated and sampled (serum, buffy coat, and ear notches) on the day of birth (DOB) and weekly for 5 consecutive weeks. The samples were subjected to diagnostic tests for BVDV—two reverse transcriptase PCR (RT-PCR) assays, two commercial real-time RT quantitative PCR (RT-qPCR), two antigen capture enzyme-linked immunosorbent assays (ACE), and immunohistochemistry (IHC)—and to HoBi-like virus-specific RT-PCR and RT-qPCR assays. …

Dens Agenesis And Cervical Vertebral Malformation In A Labrador Retriever Puppy, Elisa Salas, Henry E. Cerny, Seth P. Harris

School of Veterinary and Biomedical Sciences: Faculty Publications

Cervical vertebral malformations can cause acute or progressive pain, paralysis, and potentially death. Herein we present a case report of dens agenesis; cervical vertebral malformations of C1, C2, C6, and C7; subluxation of C1 and C2 and C4 and C5; and associated degenerative myelopathy in a 5-month-old female Labrador Retriever puppy. We additionally review current knowledge regarding pathogenesis and treatment.

Generation And Screening Of A Comprehensive Mycobacterium Avium Subsp. Paratuberculosis Transposon Mutant Bank, Govardhan Rathnaiah, Elise A. Lamont, N. Beth Harris, Robert J. Fenton, Denise K. Zinniel, Xiaofei Liu, Josh Sotos, Zhengyu Feng, Ayala Livneh-Kol, Nahum Y. Shpigel, Charles J. Czuprynski, Srinand Sreevatsan, Raul G. Barletta

School of Veterinary and Biomedical Sciences: Faculty Publications

Mycobacterium avium subsp. paratuberculosis (MAP) is the etiologic agent of Johne’s Disease in ruminants. This enteritis has significant economic impact and world wide distribution. Vaccination is one of the most cost effective infectious disease control measures. Unfortunately, current vaccines reduce clinical disease and shedding, but are of limited efficacy and do not provide long-term protective immunity. Several strategies have been followed to mine the MAP genome for virulence determinants that could be applied to vaccine and diagnostic assay developent. In this study, a comprehensive mutant bank of 13,536 MAP K-10 Tn5367 mutants (P>95% )was constructed and screened in …

Moraxella Spp. Isolated From Field Outbreaks Of Infectious Bovine Keratoconjunctivitis: A Retrospective Study Of Case Submissions From 2010 To 2013, John Dustin Loy, Bruce W. Brodersen

School of Veterinary and Biomedical Sciences: Faculty Publications

Infectious bovine keratoconjunctivitis (IBK), also known as pinkeye, is the most costly eye disease of cattle. The principal etiologic agent of IBK is the Gram-negative bacterium Moraxella bovis. However, there have been reports of IBK outbreaks associated with Moraxella bovoculi. A retrospective study of IBK diagnostic cases submitted from July 1, 2010, through October 31, 2013, was conducted. Included in the study were 1,042 Moraxella isolates from 1,538 swabs of lacrimal secretions collected from 282 herds from 30 U.S. states. Moraxella isolates were identified to the species level and were composed of M. bovoculi (701 isolates), M. bovis …

Sjl Mice Infected With Acanthamoeba Castellanii Develop Central Nervous System Autoimmunity Through The Generation Of Cross-Reactive T Cells For Myelin Antigens, Jay Reddy, Chandirasegaran Massilamany, Francine Marciano-Cabral, Bruno Da Rocha-Azevedo, Melissa Jamerson, Arunakumar Gangaplara, David Steffen, Rana Zabad, Zsolt Illes, Raymond Sobel

School of Veterinary and Biomedical Sciences: Faculty Publications

We recently reported that Acanthamoeba castellanii (ACA), an opportunistic pathogen of the central nervous system (CNS) possesses mimicry epitopes for proteolipid protein (PLP) 139–151 and myelin basic protein 89–101, and that the epitopes induce experimental autoimmune encephalomyelitis (EAE) in SJL mice reminiscent of the diseases induced with their corresponding cognate peptides. We now demonstrate that mice infected with ACA also show the generation of crossreactive T cells, predominantly for PLP 139–151, as evaluated by T cell proliferation and IAs/dextramer staining. We verified that PLP 139–151-sensitized lymphocytes generated in infected mice contained a high proportion of T helper 1 cytokineproducing cells, …

Glutaredoxin-2 Is Required To Control Oxidative Phosphorylation In Cardiac Muscle By Mediating Deglutathionylation Reactions, Mary-Ellen Harper, Ryan J. Mailloux, Jian Ying Xuan, Skye Mcbride, Wael Maharsy, Stephanie Thorn, Chet E. Holterman, Christopher R.J. Kennedy, Peter Rippstein, Robert Dekemp, Jean Da Silva, Mona Nemer, Marjorie Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

Glutaredoxin-2 (Grx2) modulates the activity of several mitochondrial proteins in cardiac tissue by catalyzing deglutathionylation reactions. However, it remains uncertain whether Grx2 is required to control mitochondrial ATP output in heart. Here, we report that Grx2 plays a vital role modulating mitochondrial energetics and heart physiology by mediating the deglutathionylation of mitochondrial proteins. Deletion of Grx2 (Grx2−/−) decreased ATP production by complex I-linked substrates to half that in wild type (WT) mitochondria. Decreased respiration was associated with increased complex I glutathionylation diminishing its activity. Tissue glucose uptake was concomitantly increased. Mitochondrial ATP output and complex I activity could be recovered …

Evaluating The Clinical And Physiological Effects Of Long Term Ultraviolet B Radiation On Guinea Pigs (Cavia Porcellus), Megan K. Watson, Adam W. Stern, Amber L. Labelle, Stephen Joslyn, Timonthy M. Fan, Katie Leister, Micah Kohles, Kemba Marshall, Mark A. Mitchell

School of Veterinary and Biomedical Sciences: Faculty Publications

Vitamin D is an important hormone in vertebrates. Most animals acquire this hormone through their diet, secondary to exposure to ultraviolet B (UVB) radiation, or a combination thereof. The objectives for this research were to evaluate the clinical and physiologic effects of artificial UVB light supplementation on guinea pigs (Cavia porcellus) and to evaluate the long-term safety of artificial UVB light supplementation over the course of six months. Twelve juvenile acromelanic Hartley guinea pigs were randomly assigned to one of two treatment groups: Group A was exposed to 12 hours of artificial UVB radiation daily and Group B …

Light Stimulates The Mouse Adrenal Through A Retinohypothalamic Pathway Independent Of An Effect On The Clock In The Suprachiasmatic Nucleus, Silke Kiessling, Patricia J. Sollars, Gary E. Pickard

School of Veterinary and Biomedical Sciences: Faculty Publications

The brain’s master circadian pacemaker resides within the hypothalamic suprachiasmatic nucleus (SCN). SCN clock neurons are entrained to the day/night cycle via the retinohypothalamic tract and the SCN provides temporal information to the central nervous system and to peripheral organs that function as secondary oscillators. The SCN clock-cell network is thought to be the hypothalamic link between the retina and descending autonomic circuits to peripheral organs such as the adrenal gland, thereby entraining those organs to the day/night cycle. However, there are at least three different routes or mechanisms by which retinal signals transmitted to the hypothalamus may be conveyed …

Protective Humoral Immune Response Induced By An Inactivated Porcine Reproductive And Respiratory Syndrome Virus Expressing The Hypo-Glycosylated Glycoprotein 5, Jung-Ah Lee, Byungjoon Kim, Fernando A. Osorio, Asit K. Pattnaik, Nak-Hyung Lee, Sang-Won Lee, Seung-Yong Park, Chang-Seon Song, In-Soo Choi, Joong-Bok Lee

School of Veterinary and Biomedical Sciences: Faculty Publications

Porcine reproductive and respiratory syndrome (PRRS) causes significant economic losses to the swine industry worldwide. Although inactivated and live vaccines are commercially available for the control of PRRS, both types of vaccine have not always proven successful in terms of generating a protective immune response, particularly in the case of inactivated vaccines. In this study, we tested whether an inactivated vaccine could induce a humoral immune response to PRRS during a homologous challenge. Amino acid substitutions were introduced into glycoprotein (GP) 5 of the FL12 strain of the PRRS virus (PRRSV) using site-directed mutagenesis with a pFL12 infectious clone. The …

Noninvasive Assessment Of Cardiac Abnormalities In Experimental Autoimmune Myocarditis By Magnetic Resonance Microscopy Imaging In The Mouse, Chandirasegara Massilamany, Vahid Khalilzad-Sharghi, Arunakumar Gangaplara, David Steffen, Shadi F. Othman, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Myocarditis is an inflammation of the myocardium, but only ~10% of those affected show clinical manifestations of the disease. To study the immune events of myocardial injuries, various mouse models of myocarditis have been widely used. This study involved experimental autoimmune myocarditis (EAM) induced with cardiac myosin heavy chain (Myhc)-α 334-352 in A/J mice; the affected animals develop lymphocytic myocarditis but with no apparent clinical signs. In this model, the utility of magnetic resonance microscopy (MRM) as a non-invasive modality to determine the cardiac structural and functional changes in animals immunized with Myhc-α 334-352 is shown. EAM and healthy mice …

Intricacies Of Cardiac Damage In Coxsackievirus B3 Infection: Implications For Therapy, Chandirasegara Massilamany, Arunakumar Gangaplara, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Heart disease is the leading cause of death in humans, and myocarditis is one predominant cause of heart failure in young adults. Patients affected with myocarditis can develop dilated cardiomyopathy (DCM), a common reason for heart transplantation, which to date is the only viable option for combatting DCM. Myocarditis/DCM patients show antibodies to coxsackievirus B (CVB)3 and cardiac antigens, suggesting a role for CVB-mediated autoimmunity in the disease pathogenesis; however, a direct causal link remains to be determined clinically. Experimentally, myocarditis can be induced in susceptible strains of mice using the human isolates of CVB3, and the disease pathogenesis of …

In Situ Detection Of Autoreactive Cd4 T Cells In Brain And Heart Using Major Histocompatibility Complex Class Ii Dextramers, Chandirasegaran Massilamany, Arunakumar Gangaplara, Ting Jia, Christian Elowsky, Qingsheng Li, You Zhou, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

This report demonstrates the use of major histocompatibility complex (MHC) class II dextramers for detection of autoreactive CD4 T cells in situ in myelin proteolipid protein (PLP) 139-151-induced experimental autoimmune encephalomyelitis (EAE) in SJL mice and cardiac myosin heavy chain-α (Myhc) 334-352-induced experimental autoimmune myocarditis (EAM) in A/J mice. Two sets of cocktails of dextramer reagents were used, where dextramers+ cells were analyzed by laser scanning confocal microscope (LSCM): EAE, IAs/PLP 139-151 dextramers (specific)/anti- CD4 and IAs/Theiler’s murine encephalomyelitis virus (TMEV) 70-86 dextramers (control)/anti-CD4; and EAM, IAk/Myhc 334-352 dextramers/ anti-CD4 and IAk/bovine ribonuclease (RNase) 43-56 dextramers (control)/anti-CD4. LSCM analysis of …

The Catabolite Control Protein E (Ccpe) Affects Virulence Determinant Production And Pathogenesis Of Staphylococcus Aureus, Torsten Hartmann, Grégory Baronian, Nadine Nippe, Meike Voss, Bettina Schulthess, Christiane Wolz, Janina Eisenbeis, Kerstin Schmidt-Hohagen, Rosmarie Gaupp, Cord Sunderkötter, Christoph Beisswenger, Robert Bals, Greg A. Somerville, Mathias Herrmann, Virginie Molle, Markus Bischoff

School of Veterinary and Biomedical Sciences: Faculty Publications

Carbon metabolism and virulence determinant production are often linked in pathogenic bacteria, and several regulatory elements have been reported to mediate this linkage in Staphylococcus aureus. Previously, we described a novel protein, catabolite control protein E (CcpE) that functions as a regulator of the tricarboxylic acid cycle. Here we demonstrate that CcpE also regulates virulence determinant biosynthesis and pathogenesis. Specifically, deletion of ccpE in S. aureus strain Newman revealed that CcpE affects transcription of virulence factors such as capA, the first gene in the capsule biosynthetic operon; hla, encoding α-toxin; and psmα, encoding the phenol-soluble modulin cluster α. Electrophoretic mobility …

Altered Entrainment To The Day/Night Cycle Attenuates The Daily Rise In Circulating Corticosterone In The Mouse, Patricia J. Sollars, Michael J. Weiser, Andrea E. Kudwa, Jayne R. Bramley, Malcolm D. Ogilvie, Robert L. Spencer, Robert J. Handa, Gary E. Pickard

School of Veterinary and Biomedical Sciences: Faculty Publications

The suprachiasmatic nucleus (SCN) is a circadian oscillator entrained to the day/night cycle via input from the retina. Serotonin (5-HT) afferents to the SCN modulate retinal signals via activation of 5-HT_1B receptors, decreasing responsiveness to light. Consequently, 5-HT_1B receptor knockout (KO) mice entrain to the day/night cycle with delayed activity onsets. Since circulating corticosterone levels exhibit a robust daily rhythm peaking around activity onset, we asked whether delayed entrainment of activity onsets affects rhythmic corticosterone secretion. Wheel-running activity and plasma corticosterone were monitored in mice housed under several different lighting regimens. Both duration of the light:dark cycle (T …