Biochemistry, Biophysics, and Structural Biology Commons^™

Hyperthermia Induces Therapeutic Effectiveness And Potentiates Adjuvant Therapy With Nontargeted And Targeted Drugs In An In Vitro Model Of Human Malignant Melanoma, T. Mantso, S. Vasileiadis, I. Anestopoulos, G. P. Voulgaridou, E. Lampri, S. Botaitis, E. N. Kontomanolis, C. Simopoulos, G. Goussetis, R. Franco, K. Chlichlia, A. Pappa, M. I. Panayiotidis

School of Veterinary and Biomedical Sciences: Faculty Publications

In the present study, we have aimed to characterize the intrinsic, extrinsic and ER-mediated apoptotic induction by hyperthermia in an in vitro model of human malignant melanoma and furthermore, to evaluate its therapeutic effectiveness in an adjuvant therapeutic setting characterized by combinational treatments with non-targeted (Dacarbazine & Temozolomide) and targeted (Dabrafenib & Vemurafenib) drugs. Overall, our data showed that both low (43 °C) and high (45 °C) hyperthermic exposures were capable of inducing cell death by activating all apoptotic pathways but in a rather distinct manner. More specifically, low hyperthermia induced extrinsic and intrinsic apoptotic pathways both of which activated …

Epitope Mapping Of Serca2a Identifies An Antigenic Determinant That Induces Mainly Atrial Myocarditis In A/J Mice, Bharathi Krishnan, Chandirasegara Massilamany, Rakesh H. Basavalingappa, Arunakumar Gangaplara, Rajkumar Rajasekaran, Muhammad Z. Afzal, Vahid Khalilzad-Sharghi, You Zhou, Jean-Jack Riethoven, Shyam S. Nandi, Paras K. Mishra, Raymond A. Sobel, Jennifer L. Strande, David Steffen, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Sarcoplasmic/endoplasmic reticulum Ca²⁺ adenosine triphosphatase (SERCA)2a, a critical regulator of calcium homeostasis, is known to be decreased in heart failure. Patients with myocarditis or dilated cardiomyopathy develop autoantibodies to SERCA2a suggesting that they may have pathogenetic significance. In this report, we describe epitope mapping analysis of SERCA2a in A/J mice that leads us to make five observations: 1) SERCA2a contains multiple T cell epitopes that induce varying degrees of myocarditis. One epitope, SERCA2a 971–990, induces widespread atrial inflammation without affecting noncardiac tissues; the cardiac abnormalities could be noninvasively captured by echocardiography, electrocardiography, and magnetic resonance microscopy imaging. 2) SERCA2a …

Circadian Behavioral Responses To Light And Optic Chiasm-Evoked Glutamatergic Epscs In The Suprachiasmatic Nucleus Of Iprgc Conditional Vglut2 Knock-Out Mice, Michael G. Moldavan, Patricia J. Sollars, Michael R. Lasarev, Charles N. Allen, Gary E. Pickard

School of Veterinary and Biomedical Sciences: Faculty Publications

Intrinsically photosensitive retinal ganglion cells (ipRGCs) innervate the hypothalamic suprachiasmatic nucleus (SCN), a circadian oscillator that functions as a biological clock. ipRGCs use vesicular glutamate transporter 2 (vGlut2) to package glutamate into synaptic vesicles and light-evoked resetting of the SCN circadian clock is widely attributed to ipRGC glutamatergic neurotransmission. Pituitary adenylate cyclase-activating polypeptide (PACAP) is also packaged into vesicles in ipRGCs and PACAP may be coreleased with glutamate in the SCN. vGlut2 has been conditionally deleted in ipRGCs in mice [conditional knock-outs (cKOs)] and their aberrant photoentrainment and residual attenuated light responses have been ascribed to ipRGC PACAP release. However, …

Novel Docosahexaenoic Acid Ester Of Phloridzin Inhibits Proliferation And Triggers Apoptosis In An In Vitro Model Of Skin Cancer, Theodora Mantso, Dimitrios T. Trafalis, Sotiris Botaitis, Rodrigo Franco, Aglaia Pappa, H. P. Vasantha Rupasinghe, Mihalis I. Panayiotidis

School of Veterinary and Biomedical Sciences: Faculty Publications

Skin cancer is among the most common cancer types accompanied by rapidly increasing incidence rates, thus making the development of more efficient therapeutic approaches a necessity. Recent studies have revealed the potential role of decosahexaenoic acid ester of phloridzin (PZDHA) in suppressing proliferation of liver, breast, and blood cancer cell lines. In the present study, we investigated the cytotoxic potential of PZDHA in an in vitro model of skin cancer consisting of melanoma (A375), epidermoid carcinoma (A431), and non-tumorigenic (HaCaT) cell lines. Decosahexaenoic acid ester of phloridzin led to increased cytotoxicity in all cell lines as revealed by cell viability …

Differential Modulation Of Human Gabac‑Ρ1 Receptor By Sulfur‑Containing Compounds Structurally Related To Taurine, Lenin David Ochoa‑De La Paz, Martin González‑Andrade, Herminia Pasantes‑Morales, Rodrigo Franco, Rubén Zamora‑Alvarado, Edgar Zenteno, Hugo Quiroz‑Mercado, Roberto Gonzales‑Salinas, Rosario Gulias‑Cañizo

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: The amino acid taurine (2-Aminoethanesulfonic acid) modulates inhibitory neurotransmitter receptors. This study aimed to determine if the dual action of taurine on GABAC- ρ1R relates to its structure. To address this, we tested the ability of the structurally related compounds homotaurine, hypotaurine, and isethionic acid to modulate GABAC- ρ1R.

Results: In Xenopus laevis oocytes, hypotaurine and homotaurine partially activate heterologously expressed GABAC- ρ1R, showing an increment in its deactivation time with no changes in channel permeability, whereas isethionic acid showed no effect. Competitive assays suggest that hypotaurine and homotaurine compete for the GABA-binding site. In addition, their effects were …

Tellurite Resistance In Shiga Toxin-Producing Escherichia Coli , Gentry L. Lewis, Quentin R. Jorgensen, John Dustin Loy, Rodney A. Moxley

School of Veterinary and Biomedical Sciences: Faculty Publications

Potassium tellurite ( K₂TeO₃) is an effective selective agent for O157:H7 Shiga toxin-producing Escherichia coli (STEC), whereas tellurite resistance in non-O157 STEC is variable with information on O45 minimal. High-level K₂TeO₃ resistance in STEC is attributable to the ter gene cluster with terD an indicator of the cluster’s presence. Polymerase chain reactions for terD and K₂TeO₃ minimum inhibitory concentration (MIC) determinations in broth cultures were conducted on 70 STEC and 40 non-STEC control organisms. Sixty-six STEC strains (94.3%) were terD+ compared to 28 control organisms (70.0%; P < 0.001). The prevalence of terD in …

Coordinated Regulation Of Transcription By Ccpa And The Staphylococcus Aureus Twocomponent System Hptrs, Joseph M. Reed, Sean Olson, Danielle F. Brees, Caitlin E. Griffin, Ryan A. Grove, Paul J. Davis, Stephen D. Kachman, Jiri Adamec, Greg A. Somerville

School of Veterinary and Biomedical Sciences: Faculty Publications

The success of Staphylococcus aureus as a pathogen is due in part to its ability to adapt to changing environmental conditions using signal transduction pathways, such as metaboliteresponsive regulators and two-component systems. S. aureus has a two-component system encoded by the gene pair sav0224 (hptS) and sav0223 (hptR) that regulate the hexose phosphate transport (uhpT) system in response to extracellular glucose-6-phosphate. Glycolytic intermediates such as glucose-6-phosphate are important carbon sources that also modulate the activity of the global metabolite-responsive transcriptional regulator CcpA. Because uhpT has a putative CcpA binding site in its promoter and …

Efficacy Of Oral Administration Of Sodium Iodide To Prevent Bovine Respiratory Disease Complex, B. M. Shoemake, B. L. Vander Ley, B. W. Newcomer, M. C. Heller

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: The prevention of bovine respiratory disease complex (BRD) in beef cattle is important to maintaining health and productivity of calves in feeding operations.

Objective: Determine whether BRD bacterial and viral pathogens are susceptible to the lactoperoxidase/hydrogen peroxide/ iodide (LPO/H₂O₂/I^-) system in vitro and to determine whether the oral administration of sodium iodide (NaI) could achieve sufficient concentrations of iodine (I) in the respiratory secretions of weaned beef calves to inactivate these pathogens in vivo.

Animals: Sixteen weaned, apparently healthy, commercial beef calves from the University of Missouri, College of Veterinary Medicine teaching herd. …

Development Of Septic Polysynovitis And Uveitis In Foals Experimentally Infected With Rhodococcus Equi, Laura Huber, Steeve Giguère, Londa J. Berghaus, Amanda Hanafi, Sarah Vitosh-Sillman, Sarah L. Czerwinski

School of Veterinary and Biomedical Sciences: Faculty Publications

Rhodococcus equi is one of the most important causes of disease in foals. Infection is typically characterized by pyogranulomatous pneumonia although extrapulmonary infections occur occasionally. Uveitis and polysynovitis have been reported in foals naturally infected with R. equi and are thought to be the result of an immune-mediated process. However, the pathogenesis of these conditions is poorly understood. The objectives of this study were to document the occurrence of uveitis and polysynovitis after experimental infection with R. equi and to determine if these disorders are the direct result of infection at these sites. Foals between 3 and 4 weeks of …

Alkaline Stabilization Of Manure Slurry Inactivates Porcine Epidemic Diarrhea Virus, Erin E. Stevens, Daniel N. Miller, Bethany A. Brittenham, Sarah J. Vitosh-Sillman, Bruce W. Brodersen, Virginia L. Jin, John D. Loy, Amy M. Schmidt

School of Veterinary and Biomedical Sciences: Faculty Publications

Hydrated lime manure treatment was evaluated to determine porcine epidemic diarrhea virus (PEDV) susceptibility to alkaline stabilization. At pH 10, PEDV decreased (quantitative polymerase chain reaction) and lost infectivity (swine bioassay). Although ammonium decreased above pH 9 (up to 25%), alkaline stabilization managed to control potential infection from manure sources.

Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry Identification Of Moraxella Bovoculi And Moraxella Bovis Isolates From Cattle, Kara Robbins, Aaron M. Dickey, Michael L. Clawson, John Dustin Loy

School of Veterinary and Biomedical Sciences: Faculty Publications

Infectious bovine keratoconjunctivitis (IBK) is an economically significant disease caused by Moraxella bovis. Moraxella bovoculi, although not reported to cause IBK, has been isolated from the eyes of cattle diagnosed with IBK. Identification of M. bovis and M. bovoculi can be performed using biochemical or DNA-based approaches, both of which may be time consuming and inconsistent between laboratories. We conducted a comparative evaluation of M. bovoculi and M. bovis identification using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with a database provided by Bruker Daltonics (termed the BDAL database), the BDAL database supplemented with spectra generated in …

Complete Genome Sequence Of Moraxella Bovis Strain Epp-63 (300), An Etiologic Agent Of Infectious Bovine Keratoconjunctivitis, John Dustin Loy, Aaron M. Dickey, Michael L. Clawson

School of Veterinary and Biomedical Sciences: Faculty Publications

We report here the complete closed genome sequence of Moraxella bovis strain Epp-63 (300) (Epp63). This strain was isolated from an infectious bovine keratoconjunctivitis (IBK) case in 1963. Since then, Epp63 has been used extensively for IBK research. Consequently, the genome sequence of Epp63 should help elucidate IBK host-pathogen interactions.

Development Of A Multiplex Real-Time Pcr Assay Using Two Thermocycling Platforms For Detection Of Major Bacterial Pathogens Associated With Bovine Respiratory Disease Complex From Clinical Samples, John Dustin Loy, Laura Leger, Aspen M. Workman, Michael L. Clawson, Ece Bulut, Bing Wang

School of Veterinary and Biomedical Sciences: Faculty Publications

Bovine respiratory disease complex (BRDC) is one of the most significant diseases of cattle. Bacterial pathogens involved in BRDC include Mannheimia haemolytica, Mycoplasma bovis, Histophilus somni, and Pasteurella multocida. We developed and evaluated a multiplexed real-time hydrolysis probe (rtPCR) assay using block-based Peltier and rotary-based thermocycling on lung tissue, nasal swabs, and deep nasopharyngeal swabs. The rtPCR results were compared to culture or a gel-based M. bovis PCR using statistical analysis to determine optimum quantification cycle (Cq) cutoffs to maximize agreement. The limits of detection were 1.2–12 CFU/reaction for each pathogen. M. haemolytica was the most prevalent organism detected …

Whole Genome Sequencing Of Moraxella Bovoculi Reveals High Genetic Diversity And Evidence For Interspecies Recombination At Multiple Loci, Aaron M. Dickey, Gennie Schuller, John D. Loy, Michael L. Clawson

School of Veterinary and Biomedical Sciences: Faculty Publications

Moraxella bovoculi is frequently cultured from the ocular secretions and conjunctiva of cattle with Infectious Bovine Keratoconjunctivitis (IBK). Previous work has shown that single nucleotide polymorphism (SNP) diversity in this species is quite high with 81,284 SNPs identified in eight genomes representing two distinct genotypes isolated from IBK affected eyes (genotype 1) and the nasopharynx of cattle without clinical IBK signs (genotype 2), respectively. The goals of this study were to identify SNPs from a collection of geographically diverse and epidemiologically unlinked M. bovoculi strains from the eyes of IBK positive cattle (n = 183) and another from the eyes …

Using Art And Story To Explore How Primary School Students In Rural Tanzania Understand Planetary Health: A Qualitative Analysis, Elizabeth Vanwormer, Jesca Mlawa, Elizabeth Komba, Christopher Gustafson, Hilda Mrema, Jenny M. Dauer

School of Veterinary and Biomedical Sciences: Faculty Publications

Background The global planetary health community increasingly recognises the need to prepare students to investigate and address connections between environmental change and human health. As we strive to support education on planetary health themes for students of all ages, understanding students’ concepts of linkages between the health of people and animals, and their shared environments might advance educational approaches. Children living in villages bordering Ruaha National Park in Iringa Region, Tanzania, have direct experience of these connections as they share a water-stressed but biodiverse environment with domestic animals and wildlife. Livelihoods in these villages depend predominantly on crop and livestock …