Removal of chronic Mycoplasma ovipneumoniae carrier ewes eliminates pneumonia in a bighorn sheep population

1. Chronic pathogen carriage is one mechanism that allows diseases to persist in populations. We hypothesized that persistent or recurrent pneumonia in bighorn sheep (Ovis canadensis) populations may be caused by chronic carriers of Mycoplasma ovipneumoniae (Mo). Our experimental approach allowed us to address a conservation need while investigating the role of chronic carriage in disease persistence.
2. We tested our hypothesis in two bighorn sheep populations in South Dakota, USA. We identified and removed Mo chronic carriers from the Custer State Park (treatment) population. Simultaneously, we identified carriers but did not remove them from the Rapid City population (control). We predicted removal would result in decreased pneumonia, mortality, and Mo prevalence. Both population ranges had similar habitat and predator communities but were sufficiently isolated to preclude intermixing.
3. We classified chronic carriers as adults that consistently tested positive for Mo carriage over a 20‐month sampling period (n = 2 in the treatment population; n = 2 in control population).
4. We failed to detect Mo or pneumonia in the treatment population after chronic carrier removal, while both remained in the control. Mortality hazard for lambs was reduced by 72% in the treatment population relative to the control (CI = 36%, 91%). There was also a 41% reduction in adult mortality hazard attributable to the treatment, although this was not statistically significant (CI = 82% reduction, 34% increase).
5. Synthesis and Applications: These results support the hypothesis that Mo is a primary causative agent of persistent or recurrent respiratory disease in bighorn sheep populations and can be maintained by a few chronic carriers. Our findings provide direction for future research and management actions aimed at controlling pneumonia in wild sheep and may apply to other diseases.

     

CD4+CD25+ regulatory T cell repertoire formation shaped by differential presentation of peptides from a self-antigen

We have used TCR transgenic mice directed to different MHC class II-restricted determinants from the influenza virus hemagglutinin (HA) to analyze how specificity for self-peptides can shape CD4+CD25+ regulatory T (Treg) cell formation. We show that substantial increases in the number of CD4+CD25+ Treg cells can occur when an autoreactive TCR directed to a major I-E(d)-restricted determinant from HA develops in mice expressing HA as a self-Ag, and that the efficiency of this process is largely unaffected by the ability to coexpress additional TCR alpha-chains. This increased formation of CD4+CD25+ Treg cells in the presence of the self-peptide argues against models that postulate selective survival rather than induced formation as mechanisms of CD4+CD25+ Treg cell formation. In contrast, T cells bearing a TCR directed to a major I-A(d)-restricted determinant from HA underwent little or no selection to become CD4+CD25+ Treg cells in mice expressing HA as a self-Ag, correlating with inefficient processing and presentation of the peptide from the neo-self-HA polypeptide. These findings show that interactions with a self-peptide can induce thymocytes to differentiate along a pathway to become CD4+CD25+ Treg cells, and that peptide editing by DM molecules may help bias the CD4+CD25+ Treg cell repertoire away from self-peptides that associate weakly with MHC class II molecules.     

Immunodominance of CD4 T cells to foreign antigens is peptide intrinsic and independent of molecular context: implications for vaccine design

Immunodominance refers to the restricted peptide specificity of T cells that are detectable after an adaptive immune response. For CD4 T cells, many of the mechanisms used to explain this selectivity suggest that events related to Ag processing play a major role in determining a peptide's ability to recruit CD4 T cells. Implicit in these models is the prediction that the molecular context in which an antigenic peptide is contained will impact significantly on its immunodominance. In this study, we present evidence that the selectivity of CD4 T cell responses to peptides contained within protein Ags is not detectably influenced by the location of the peptide in a given protein or the primary sequence of the protein that bears the test peptide. We have used molecular approaches to change the location of peptides within complex protein Ags and to change the flanking sequences that border the peptide epitope to now include a protease site, and find that immunodominance or crypticity of a peptide observed in its native protein context is preserved. Collectively, these results suggest immunodominance of peptides contained in complex Ags is due to an intrinsic factor of the peptide, based upon the affinity of that peptide for MHC class II molecules. These findings are discussed with regard to implications for vaccine design.     

Recovery of benthic marine communities from the end‐Permian mass extinction at the low latitudes of eastern Panthalassa

Based on the quantitative community analysis using species‐level identifications, we track the restoration of benthic ecosystems after the end‐Permian mass extinction throughout the Lower Triassic of the western USA. New data on the palaeoecology of the Thaynes Group and Sinbad Formation are provided, which fill a gap between the recently studied palaeoecology of the Griesbachian–Dienerian Dinwoody Formation and the Spathian Virgin Formation. In the Sinbad Formation and Thaynes Group, 17 species (12 genera) of bivalves, 7 species and genera of gastropods and 2 species and genera of brachiopods are recognized. The new bivalve genus Confusionella (Pteriidae) is described. A comprehensive review of the whole Lower Triassic succession of benthic ecosystems of the western USA indicates that mid‐ and inner shelf environments show incipient recovery signals around the Griesbachian–Dienerian transition, during the Smithian and, most profound, during the early Spathian. Ecological data from youngest strata of the Dinwoody Formation as well as stratigraphic ranges of species suggest that the late Dienerian was likely a time interval of environmental stress for benthic ecosystems. Despite some evidence for short‐term environmental disturbances (e.g. shift of dominant taxa, transient drop in alpha‐diversity) during the Smithian–Spathian transition, benthic ecosystems did not show any notable taxonomic turnover at that time, in contrast to the major crisis that affected ammonoids and conodonts. Whereas alpha‐diversity of benthic communities generally increased throughout the Early Triassic, beta‐diversity remained low, which reflects a persistently wide environmental range of benthic species. This observation is in accordance with a recently proposed model that predicts a time lag between increasing within‐habitat diversity (alpha‐diversity) and the onset of taxonomic differentiation between habitats (beta‐diversity) during biotic recoveries from mass extinction events. The observation that beta‐diversity had not significantly increased during the Early Triassic might also provide an explanation for the comparably sluggish increase in benthic diversity during that time, which has previously been attributed to persistent environmental stress.     

Assessment of TRH as a potential MSH release stimulating factor in Xenopus laevis

This study considers the possible involvement of the tripeptide TRH (thyrotropin releasing hormone) in the physiological regulation of melanophore stimulating hormone (MSH) secretion from the pars intermedia of the toad, Xenopus laevis. TRH was shown to stimulate release of MSH from superfused neurointermediate lobes obtained from white-background adapted animals, but had no effect on secretion from lobes of black-background adapted animals. Immunohistochemical analysis revealed a rich TRH-containing neuronal network terminating in the neural lobe of the Xenopus pituitary. Plasma levels of TRH, determined with a specific radioimmunoassay, proved to be extremely high and no significant difference in this level could be found between white- and black-adapted animals. Plasma TRH probably originates from the skin, and our results show that its concentration is within the effective concentration range established for this peptide in stimulating MSH release from the pars intermedia. Therefore, while both our superfusion and immunohistochemical results argue favourably for a function of TRH in the regulation of MSH secretion, we conclude that, in any regulatory role, it would likely have to function within the pars intermedia at concentrations exceeding the high plasma values. While TRH could be involved in short-term activation of the secretory process in white-background adapted animals or in animals undergoing the initial stages of black background adaptation, our results indicate that this peptide may have no function in the maintenance of secretion from the pars intermedia of animals fully adapted to black background.     

A high utility integrated map of the pig genome

Background

The domestic pig is being increasingly exploited as a system for modeling human disease. It also has substantial economic importance for meat-based protein production. Physical clone maps have underpinned large-scale genomic sequencing and enabled focused cloning efforts for many genomes. Comparative genetic maps indicate that there is more structural similarity between pig and human than, for example, mouse and human, and we have used this close relationship between human and pig as a way of facilitating map construction.

Results

Here we report the construction of the most highly continuous bacterial artificial chromosome (BAC) map of any mammalian genome, for the pig (Sus scrofa domestica) genome. The map provides a template for the generation and assembly of high-quality anchored sequence across the genome. The physical map integrates previous landmark maps with restriction fingerprints and BAC end sequences from over 260,000 BACs derived from 4 BAC libraries and takes advantage of alignments to the human genome to improve the continuity and local ordering of the clone contigs. We estimate that over 98% of the euchromatin of the 18 pig autosomes and the X chromosome along with localized coverage on Y is represented in 172 contigs, with chromosome 13 (218 Mb) represented by a single contig. The map is accessible through pre-Ensembl, where links to marker and sequence data can be found.

Conclusion

The map will enable immediate electronic positional cloning of genes, benefiting the pig research community and further facilitating use of the pig as an alternative animal model for human disease. The clone map and BAC end sequence data can also help to support the assembly of maps and genome sequences of other artiodactyls.     

Restoration of a bighorn sheep population impeded by Mycoplasma ovipneumoniae exposure

Bighorn sheep (Ovis canadensis) were once extirpated from the Black Hills region of South Dakota, U.S.A., mirroring declining populations throughout North America. Since the 1960s, several reintroductions have occurred in the Black Hills to reestablish populations, with varying success. We translocated 26 bighorn sheep from Alberta, Canada, to the Black Hills (February 2015) to restore bighorn sheep to their historic range. Due to prior examinations of cause‐specific survival, subsequent genetic diversity and disease prevalence analyses were required to evaluate success of the restoration effort. We measured a mean allelic diversity of 5.23 (SE = 0.44 [mean number of alleles]) and an observed heterozygosity of 0.71 (SE = 0.06; expected = 0.64 ± 0.05) in the translocated individuals. Translocated bighorn sheep tested negative for Mycoplasma ovipneumoniae at capture. An autogenous vaccine was administered prior to release in an attempt to safeguard the translocated bighorn sheep from infection with a strain known to be resident in adjacent bighorn sheep populations. However, the year following the translocation, a different strain of M. ovipneumoniae was associated with a pneumonia outbreak that resulted in 57.9% mortality. Our results suggest that allelic diversity and heterozygosity were sufficient for long‐term herd establishment, reducing the potential for founder effects. However, the overwhelming mortality associated with pneumonia, via the transfer of M. ovipneumoniae from an unknown source, limited the success or our reintroduction efforts. Successful attempts to restore bighorn sheep to their historic ranges must consider and mitigate potential routes for M. ovipneumoniae transmission pre‐ and post‐reintroduction.     

Quantitative Evaluation of a Mexican and a Ghanaian Tabernaemontana Species as Alternatives to Voacanga africana for the Production of Antiaddictive Ibogan Type Alkaloids

In continuation of our efforts to provide quantitative information on antiaddictive ibogan type alkaloid‐producing Tabernaemontana species, we used gas chromatography‐mass spectrometry (GC/MS) to compare the alkaloid profiles of the barks and/or leaves of one Mexican and one African species – T. arborea and T. crassa, respectively, with the primary sources of commercially available semisynthetic ibogaine, Voacanga africana root and stem bark. The qualitative and quantitative similarities between T. arborea and V. africana barks consolidate previous reports regarding the potential of the former as a promising alternative source of voacangine and ibogaine. The results also suggest that T. crassa could be used to produce conopharyngine and ibogaline, two compounds with the same basic skeletal structure and possibly similar antiaddictive properties as ibogaine.     

From “Lists of Traits” to “Open-Mindedness”: Emerging Issues in Cultural Competence Education

The incorporation of “culture” into U.S. biomedicine has been increasing at a rapid pace over the last several decades. Advocates for “cultural competence” point to changing patient demographics and growing health disparities as they call for improved educational efforts that train health providers to care for patients from a variety of backgrounds. Medical anthropologists have long been critical of the approach to “culture” that emerges in cultural competence efforts, identifying an essentialized, static notion of culture that is conflated with racial and ethnic categories and seen to exist primarily among exotic “Others.” With this approach, culture can become a “list of traits” associated with various racial and ethnic groups that must be mastered by health providers and applied to patients as necessary. This article uses an ethnographic examination of cultural competence training to highlight recent efforts to develop more nuanced approaches to teaching culture. I argue that much of contemporary cultural competence education has rejected the “list of traits” approach and instead aims to produce a new kind of health provider who is “open-minded,” willing to learn about difference, and treats each patient as an individual. This shift, however, can ultimately reinforce behavioral understandings of culture and draw attention away from the social conditions and power differentials that underlie health inequalities.