Cultural Competence Is Everyone's Business: Embedding Cultural Competence in Curriculum Frameworks to Advance Veterinary Education.

Cultural competence in professional and research practice is important to effectively deliver animal and One Health services and programs. Veterinarians work with culturally and linguistically diverse teams, clients, and communities. Cultural perspectives on the significance and perceptions of animals and differences in consultation and engagement protocols and strategies can influence client-practitioner and researcher-community relationships, impacting animal health, welfare, and/or research outcomes. Curricula have been proposed to build cultural capacity in graduates, but these have not been reported in veterinary programs, and early attempts to integrate cultural competency into the University of Sydney veterinary curriculum lacked a formal structure and were ad hoc with respect to implementation. To address this, the authors introduced a broad curriculum framework into the University of Sydney veterinary program, which defines cultural competence, perceptions of animals, effective communication, and community engagement in a range of contexts. Cultural competency learning outcomes were described for units of study. These were contextually relevant and aligned to course learning outcomes and University of Sydney graduate qualities. Constructive alignment was achieved by linking learning outcomes to teaching and learning activities and assessment. The continuum of cultural competency underpinned mapping of cultural competency across the curriculum with staged, vertical integration of key principles. Additionally, action to engage staff, students, and stakeholders in a cultural competence agenda assisted in sustaining curriculum change. The result was integration of cultural competency across the curriculum aligning with recommendations from accrediting bodies and with best practice models in medicine, nursing, and allied health programs.

Ebselen as template for stabilization of A4V mutant dimer for motor neuron disease therapy.

Mutations to the gene encoding superoxide dismutase-1 (SOD1) were the first genetic elements discovered that cause motor neuron disease (MND). These mutations result in compromised SOD1 dimer stability, with one of the severest and most common mutations Ala4Val (A4V) displaying a propensity to monomerise and aggregate leading to neuronal death. We show that the clinically used ebselen and related analogues promote thermal stability of A4V SOD1 when binding to Cys111 only. We have developed a A4V SOD1 differential scanning fluorescence-based assay on a C6S mutation background that is effective in assessing suitability of compounds. Crystallographic data show that the selenium atom of these compounds binds covalently to A4V SOD1 at Cys111 at the dimer interface, resulting in stabilisation. This together with chemical amenability for hit expansion of ebselen and its on-target SOD1 pharmacological chaperone activity holds remarkable promise for structure-based therapeutics for MND using ebselen as a template.

Abscisic Acid as a Dominant Signal in Tomato During Salt Stress Predisposition to Phytophthora Root and Crown Rot.

Salt stress predisposes plants to Phytophthora root and crown rot in an abscisic acid (ABA)-dependent manner. We used the tomato-Phytophthora capsici interaction to examine zoospore chemoattraction and assessed expression of pathogenesis-related (PR) genes regulated by salicylic acid (SA) and jasmonic acid (JA) following a salt-stress episode. Although salt treatment enhances chemoattraction of tomato roots to zoospores, exudates from salt-stressed roots of ABA-deficient mutants, which do not display the predisposition phenotype, have a similar chemoattraction as exudates from salt-stressed, wild-type roots. This suggests that ABA action during predisposing stress enhances disease through effects on plant responses occurring after initial contact and during ingress by the pathogen. The expression of NCED1 (ABA synthesis) and TAS14 (ABA response) in roots generally corresponded to previously reported changes in root ABA levels during salt stress onset and recovery in a pattern that was not altered by infection by P. capsici. The PR genes, P4 and PI-2, hallmarks in tomato for SA and JA action, respectively, were induced in non-stressed roots during infection and strongly suppressed in infected roots exposed to salt-stress prior to inoculation. However, there was a similar proportional increase in pathogen colonization observed in salt-stressed plants relative to non-stressed plants in both wild-type and a SA-deficient nahG line. Unlike the other tomato cultivars used in this study that showed a strong predisposition phenotype, the processing tomato cv. 'Castlemart' and its JA mutants were not predisposed by salt. Salt stress predisposition to crown and root rot caused by P. capsici appears to be strongly conditioned by ABA-driven mechanisms in tomato, with the stress compromising SA-and JA-mediated defense-related gene expression during P. capsici infection.

Towards depersonalized abacavir therapy: chemical modification eliminates HLA-B*57 : 01-restricted CD8+ T-cell activation.

OBJECTIVE: Exposure to abacavir is associated with T-cell-mediated hypersensitivity reactions in individuals carrying human leukocyte antigen (HLA)-B57 : 01. To activate T cells, abacavir interacts directly with endogenous HLA-B57 : 01 and HLA-B57 : 01 expressed on the surface of antigen presenting cells. We have investigated whether chemical modification of abacavir can produce a molecule with antiviral activity that does not bind to HLA-B57 : 01 and activate T cells. DESIGN: An interdisciplinary laboratory study using samples from human donors expressing HLA-B57 : 01. Researchers were blinded to the analogue structures and modelling data. METHODS: Sixteen 6-amino substituted abacavir analogues were synthesized. Computational docking studies were completed to predict capacity for analogue binding within HLA-B57 : 01. Abacavir-responsive CD8 clones were generated to study the association between HLA-B57 : 01 analogue binding and T-cell activation. Antiviral activity and the direct inhibitory effect of analogues on proliferation were assessed. RESULTS: Major histocompatibility complex class I-restricted CD8 clones proliferated and secreted IFNγ following abacavir binding to surface and endogenous HLA-B57 : 01. Several analogues retained antiviral activity and showed no overt inhibitory effect on proliferation, but displayed highly divergent antigen-driven T-cell responses. For example, abacavir and N-propyl abacavir were equally potent at activating clones, whereas the closely related analogues N-isopropyl and N-methyl isopropyl abacavir were devoid of T-cell activity. Docking abacavir analogues to HLA-B57 : 01 revealed a quantitative relationship between drug-protein binding and the T-cell response. CONCLUSION: These studies demonstrate that the unwanted T-cell activity of abacavir can be eliminated whilst maintaining the favourable antiviral profile. The in-silico model provides a tool to aid the design of safer antiviral agents that may not require a personalized medicines approach to therapy.

Predisposition in plant disease: exploiting the nexus in abiotic and biotic stress perception and response.

Predisposition results from abiotic stresses occurring prior to infection that affect susceptibility of plants to disease. The environment is seldom optimal for plant growth, and even mild, episodic stresses can predispose plants to inoculum levels they would otherwise resist. Plant responses that are adaptive in the short term may conflict with those for resisting pathogens. Abiotic and biotic stress responses are coordinated by complex signaling networks involving phytohormones and reactive oxygen species (ROS). Abscisic acid (ABA) is a global regulator in stress response networks and an important phytohormone in plant-microbe interactions with systemic effects on resistance and susceptibility. However, extensive cross talk occurs among all the phytohormones during stress events, and the challenge is discerning those interactions that most influence disease. Identifying convergent points in the stress response circuitry is critically important in terms of understanding the fundamental biology that underscores the disease phenotype as well as translating research to improve stress tolerance and disease management in production systems.

Induced resistance in tomato by SAR activators during predisposing salinity stress.

Plant activators are chemicals that induce disease resistance. The phytohormone salicylic acid (SA) is a crucial signal for systemic acquired resistance (SAR), and SA-mediated resistance is a target of several commercial plant activators, including Actigard (1,2,3-benzothiadiazole-7-thiocarboxylic acid-S-methyl-ester, BTH) and Tiadinil [N-(3-chloro-4-methylphenyl)-4-methyl-1,2,3-thiadiazole-5-carboxamide, TDL]. BTH and TDL were examined for their impact on abscisic acid (ABA)-mediated, salt-induced disease predisposition in tomato seedlings. A brief episode of salt stress to roots significantly increased the severity of disease caused by Pseudomonas syringae pv. tomato (Pst) and Phytophthora capsici relative to non-stressed plants. Root treatment with TDL induced resistance to Pst in leaves and provided protection in both non-stressed and salt-stressed seedlings in wild-type and highly susceptible NahG plants. Non-stressed and salt-stressed ABA-deficient sitiens mutants were highly resistant to Pst. Neither TDL nor BTH induced resistance to root infection by Phytophthora capsici, nor did they moderate the salt-induced increment in disease severity. Root treatment with these plant activators increased the levels of ABA in roots and shoots similar to levels observed in salt-stressed plants. The results indicate that SAR activators can protect tomato plants from bacterial speck disease under predisposing salt stress, and suggest that some SA-mediated defense responses function sufficiently in plants with elevated levels of ABA.

Arachidonic acid: an evolutionarily conserved signaling molecule modulates plant stress signaling networks.

Fatty acid structure affects cellular activities through changes in membrane lipid composition and the generation of a diversity of bioactive derivatives. Eicosapolyenoic acids are released into plants upon infection by oomycete pathogens, suggesting they may elicit plant defenses. We exploited transgenic Arabidopsis thaliana plants (designated EP) producing eicosadienoic, eicosatrienoic, and arachidonic acid (AA), aimed at mimicking pathogen release of these compounds. We also examined their effect on biotic stress resistance by challenging EP plants with fungal, oomycete, and bacterial pathogens and an insect pest. EP plants exhibited enhanced resistance to all biotic challenges, except they were more susceptible to bacteria than the wild type. Levels of jasmonic acid (JA) were elevated and levels of salicylic acid (SA) were reduced in EP plants. Altered expression of JA and SA pathway genes in EP plants shows that eicosapolyenoic acids effectively modulate stress-responsive transcriptional networks. Exogenous application of various fatty acids to wild-type and JA-deficient mutants confirmed AA as the signaling molecule. Moreover, AA treatment elicited heightened expression of general stress-responsive genes. Importantly, tomato (Solanum lycopersicum) leaves treated with AA exhibited reduced susceptibility to Botrytis cinerea infection, confirming AA signaling in other plants. These studies support the role of AA, an ancient metazoan signaling molecule, in eliciting plant stress and defense signaling networks.

Abscisic acid in salt stress predisposition to phytophthora root and crown rot in tomato and chrysanthemum.

Plants respond to changes in the environment with complex signaling networks, often under control of phytohormones that generate positive and negative crosstalk among downstream effectors of the response. Accordingly, brief dehydration stresses such as salinity and water deficit, which induce a rapid and transient systemic increase in levels of abscisic acid (ABA), can influence disease response pathways. ABA has been associated with susceptibility of plants to bacteria, fungi, and oomycetes but relatively little attention has been directed at its role in abiotic stress predisposition to root pathogens. This study examines the impact of brief salinity stress on infection of tomato and chrysanthemum roots by Phytophthora spp. Roots of plants in hydroponic culture exposed to a brief episode of salt (sodium chloride) stress prior to or after inoculation were severely diseased relative to nonstressed plants. Tomato roots remained in a predisposed state up to 24 h following removal from the stress. An increase in root ABA levels in tomato preceded or temporally paralleled the onset of stress-induced susceptibility, with levels declining in roots prior to recovery from the predisposed state. Exogenous ABA could substitute for salt stress and significantly enhanced pathogen colonization and disease development. ABA-deficient tomato mutants lacked the predisposition response, which could be restored by complementation of the mutant with exogenous ABA. In contrast, ethylene, which exacerbates disease symptoms in some host-parasite interactions, did not appear to contribute to the predisposition response. Thus, several lines of evidence support ABA as a critical and dominant factor in the salinity-induced predisposition to Phytophthora spp. infection.