Veterinary Pathobiology publications (MU)
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Items in this collection are the scholarly output of the Department of Veterinary Pathobiology faculty, staff, and students, either alone or as co-authors, and which may or may not have been published in an alternate format. Items may contain more than one file type.
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Item Shift from primary pneumonic to secondary septicemic plague by decreasing the volume of intranasal challenge with Yersinia pestis in the murine model(Public Library of Science, 2019) Olson, R. M.; Anderson, D. M.; Veterinary PathobiologyYersinia pestis is the causative agent of pneumonic plague, a disease involving uncontrolled bacterial growth and host immunopathology. Secondary septicemic plague commonly occurs as a consequence of the host inflammatory response that causes vasodilation and vascular leakage, which facilitates systemic spread of the bacteria and the colonization of secondary tissues. The mortality rates of pneumonic and septicemic plague are high even when antibiotics are administered. In this work, we show that primary pneumonic or secondary septicemic plague can be preferentially modeled in mice by varying the volume used for intranasal delivery of Y. pestis. Low volume intranasal challenge (10µL) of wild type Y. pestis resulted in a high frequency of lethal secondary septicemic plague, with a low degree of primary lung infection and rapid development of sepsis. In contrast, high volume intranasal challenge (30µL) yielded uniform early lung infection and primary disease and a significant increase in lethality. In a commonly used BSL2 model, high volume challenge with Y. pestis lacking the pigmentation locus (pgm-) gave 105-fold greater deposition compared to low volume challenge, yet moribund mice did not develop severe lung disease and there was no detectable difference in lethality. These data indicate the primary cause of death of mice in the BSL2 model is sepsis regardless of intranasal dosing method. Overall, these findings allow for the preferential modeling of pneumonic or septicemic plague by intranasal dosing of mice with Y. pestis.Item Yersinia pestis exploits early activation of MyD88 for growth in the lungs during pneumonic plague(American Society for Microbiology, 2019) Olson, R. M.; Dhariwala, M. O.; Mitchell, W. J.; Anderson, D. M.; Veterinary PathobiologyYersinia pestis causes bubonic, pneumonic, and septicemic plague. Although no longer responsible for pandemic outbreaks, pneumonic plague continues to be a challenge for medical treatment and has been classified as a reemerging disease in some parts of the world. In the early stage of infection, inflammatory responses are believed to be suppressed by Y. pestis virulence factors in order to prevent clearance, while later, the hyperactivation of inflammation contributes to the progression of disease. In this work, we sought to identify the host factors that mediate this process and studied the role of the Toll/interleukin 1 (IL-1) receptor adapter and major inflammatory mediator myeloid differentiation primary response 88 (MyD88) in pneumonic plague. We show that pulmonary challenge of Myd88/ mice with wild-type (WT) Y. pestis results in significant loss of pro- and anti-inflammatory cytokines and chemokines, especially gamma interferon (IFN-) and KC, in the lungs compared to that in WT mice. Bacterial growth in the lungs occurred more rapidly in the WT mice, however, indicating a role for the MyD88 response in facilitating the primary lung infection. Nevertheless, Myd88/ mice were more sensitive to lethality from secondary septicemic plague. Together these findings indicate a central role for MyD88 during the biphasic inflammatory response to pulmonary Y. pestis infection. In the early phase, low-level MyD88-dependent chemokine expression limits initial growth but facilitates Y. pestis access to a protected replicative niche. The later hyperinflammatory phase is partially MyD88 dependent and ineffective in the lungs but controls systemic infection and reduces the progression of secondary septicemic plague. CopyrightItem A homozygous ADAMTS2 nonsense mutation in a Doberman Pinscher dog with Ehlers Danlos syndrome and extreme skin fragility(Blackwell Publishing Ltd, 2019) Jaffey, J. A.; Bullock, G.; Teplin, E.; Guo, J.; Villani, N. A.; Mhlanga-Mutangadura, T.; Schnabel, R. D.; Cohn, L. A.; Johnson, G. S.; Veterinary PathobiologyAn eight-week old Doberman Pinscher was diagnosed with Ehlers Danlos syndrome based on the dog's hyper-mobile carpal, tarsal and stifle joints and abnormal skin. The skin was loose and hyper-elastic with several wounds and large atrophic scars. The dog was euthanized after a severe degloving injury from minimal trauma. A whole-genome sequence, generated with DNA from the dog's blood, contained a rare, homozygous C-to-T transition at position 2408978 on chromosome 11. This transition is predicted to alter the ADAMTS2 transcript (ADAMTS2:c.769C>T) and encode a nonsense mutation (p.Arg257Ter). Biallelic ADAMTS2 mutations have caused a type of Ehlers Danlos syndrome known as dermatosparaxis in other species.Item Validation of X-Ray Fluorescence-Measured Swine Femur Lead Against Atomic Absorption Spectrometry(National Institute of Environmental Health Sciences, 2001) Todd, Andrew C.; Moshier, Erin L.; Carroll, Spencer; Casteel, Stan W.The aim of this study was to apply the technique of 109Cd-based K-shell X-ray fluorescence (XRF) bone lead measurements to swine femurs and to validate the concentrations obtained therefrom against an independent chemical measurement of bone lead: atomic absorption spectrometry (AAS). The femurs ranged in lead concentration from 1.0 to 24.5 µg of lead per gram of ashed bone, as measured by AAS. On average, XRF overestimated AAS-measured femur lead by 2.6 µg/g [95% confidence interval (CI), 1.1-4.0 µg/g], approximately 2 µg/g poorer than that observed in studies of human tibiae. Measurements of swine femur and, by extension, of nonhuman bones may require adjustment of the XRF spectrum peak extraction method.Item Characterization of the Bovine Type I IFN Locus: Rearrangements, Expansions, and Novel Subfamilies(BMC Genomics, 2009) Walker, Angela Marie, 1978-; Roberts, R. M. (Robert Michael), 1940-The Type I interferons (IFN) have major roles in the innate immune response to viruses, a function that is believed to have led to expansion in the number and complexity of their genes, although these genes have remained confined to single chromosomal region in all mammals so far examined. IFNB and IFNE define the limits of the locus, with all other Type I IFN genes except IFNK distributed between these boundaries, strongly suggesting that the locus has broadened as IFN genes duplicated and then evolved into a series of distinct families. We have provided the first comprehensive annotation of the Type I IFN locus in Bos taurus, thereby providing an insight into the functional evolution of the Type I IFN in ruminants. The diversity and global spread of the ruminant species may have required an expansion of the Type I IFN locus and its constituent genes to provide broad anti-viral protection required for foraging and foregut fermentation.