Comparative assessment of the sensitivity of fish early-life stage, daphnia and algae to the chronic ecotoxicity of xenobiotics - perspectives for alternatives to animal testing

No-observed-effect concentrations (NOECs) are used in environmental hazard classification and labeling of chemicals and their environmental risk assessment. They are typically obtained using standard tests such as the fish early-life stage (FELS) toxicity test, the chronic Daphnia reproduction test, and the algae growth inhibition test. Given the demand to replace and reduce animal tests, we explored the impact of the FELS toxicity test on the determination of effect concentrations by comparing the FELS toxicity test and the Daphnia and algae acute or chronic toxicity tests. Lowest-observed-effect concentrations (LOECs) were used instead of NOECs for better comparison with median lethal or effect concentration data. A database of FELS toxicity data for 223 compounds was established. Corresponding Daphnia and algae toxicity tests were identified using established databases (US Environmental Protection Agency ECOTOX, Organisation for Economic Co-operation and Development QSAR Toolbox, eChemPortal, EnviroTox, and OpenFoodTox). Approximately 9.5% of the investigated compounds showed a 10-fold higher sensitivity with the FELS toxicity test in comparison with the lowest effect concentrations obtained with any of the other tests. Some of these compounds have been known or considered as endocrine disrupting, or are other non-narcotic chemicals, indicating that the higher sensitivity in the FELS toxicity test is related to a specific mechanism of action. Targeting these mechanisms by alternative test systems or endpoints, using fish embryos for instance, may allow reduction or replacement of the FELS toxicity test or may allow us to prioritize compounds for conduction of the FELS toxicity test

Mst1/2 signalling to Yap: gatekeeper for liver size and tumour development

The mechanisms controlling mammalian organ size have long been a source of fascination for biologists. These controls are needed to both ensure the integrity of the body plan and to restrict inappropriate proliferation that could lead to cancer. Regulation of liver size is of particular interest inasmuch as this organ maintains the capacity for regeneration throughout life, and is able to regain precisely its original mass after partial surgical resection. Recent studies using genetically engineered mouse strains have shed new light on this problem; the Hippo signalling pathway, first elucidated as a regulator of organ size in Drosophila, has been identified as dominant determinant of liver growth. Defects in this pathway in mouse liver lead to sustained liver overgrowth and the eventual development of both major types of liver cancer, hepatocellular carcinoma and cholangiocarcinoma. In this review, we discuss the role of Hippo signalling in liver biology and the contribution of this pathway to liver cancer in humans

Down-Regulation of Yes Associated Protein 1 Expression Reduces Cell Proliferation and Clonogenicity of Pancreatic Cancer Cells

BACKGROUND: The Hippo pathway regulates organ size by inhibiting cell proliferation and promoting cell apoptosis upon its activation. The Yes Associated Protein 1 (YAP1) is a nuclear effector of the Hippo pathway that promotes cell growth as a transcription co-activator. In human cancer, the YAP1 gene was reported as amplified and over-expressed in several tumor types. METHODS: Immunohistochemical staining of YAP1 protein was used to assess the expression of YAP1 in pancreatic tumor tissues. siRNA oligonucleotides were used to knockdown the expression of YAP1 and their effects on pancreatic cancer cells were investigated using cell proliferation, apoptosis, and anchorage-independent growth assays. The Wilcoxon signed-rank, Pearson correlation coefficient, Kendall's Tau, Spearman's Rho, and an independent two-sample t (two-tailed) test were used to determine the statistical significance of the data. RESULTS: Immunohistochemistry studies in pancreatic tumor tissues revealed YAP1 staining intensities were moderate to strong in the nucleus and cytoplasm of the tumor cells, whereas the adjacent normal epithelial showed negative to weak staining. In cultured cells, YAP1 expression and localization was modulated by cell density. YAP1 total protein expression increased in the nuclear fractions in BxPC-3 and PANC-1, while it declined in HPDE6 as cell density increased. Additionally, treatment of pancreatic cancer cell lines, BxPC-3 and PANC-1, with YAP1-targeting siRNA oligonucleotides significantly reduced their proliferation in vitro. Furthermore, treatment with YAP1 siRNA oligonucleotides diminished the anchorage-independent growth on soft agar of pancreatic cancer cells, suggesting a role of YAP1 in pancreatic cancer tumorigenesis. CONCLUSIONS: YAP1 is overexpressed in pancreatic cancer tissues and potentially plays an important role in the clonogenicity and growth of pancreatic cancer cells

Parent and Adolescent Perceptions of Adolescent Career Development Tasks and Vocational Identity

We surveyed Australian adolescents and parents to test differences and congruence in perceptions of adolescent career development tasks (career planning, exploration, certainty, and world-of-work knowledge) and vocational identity. We found that, for adolescents (N = 415), career development tasks (not career exploration) explained 48% of the variance in vocational identity; for parents (N = 415), this was 38% (not world-of-work knowledge). Parent perceptions of career development tasks did not explain additional variance in adolescent vocational identity. There were moderate correlations between adolescent and parent perceptions of career development tasks and vocational identity, suggesting meaningful, but not substantial, congruence of perceptions. The findings provide useful insights into the understanding of, and relationship between, parent and adolescent perceptions of adolescent career development tasks and vocational identity, which suggest avenues for interventions with adolescents and parentsGriffith Business School, Dept of Employment Relations and Human ResourcesFull Tex

Assessment of diclofenac LC50 reference values in juvenile and embryonic stages of the zebrafish (Danio rerio)

The aim of the study was to compare the acute toxicity of diclofenac to juvenile and embryonic stages of the zebrafish (Danio rerio). Acute toxicity tests were performed on the aquarium fish Danio rerio, which is one of the model organisms most commonly used in toxicity testing. The tests were performed using a semi-static method according to OECD guideline No. 203 (Fish, acute toxicity test). Embryo toxicity tests were performed in zebrafish embryos (Danio rerio) in compliance with OECD No. 212 methodology (Fish, short-term toxicity test on embryo and sac-fry stages). The results were subjected to a probit analysis using the EKO-TOX 5.2 programme to determine 96hLC50 and 144hLC50 (median lethal concentration, 50% mortality after a 96 h or 144 h interval, respectively) values of diclofenac. The statistical significance of the difference between LC50 values in juvenile and embryonic stages of Danio rerio was tested using the Mann-Whitney non-parametric test implemented in the Unistat 5.1 programme. The LC50 mean value of diclofenac was 166.6 ± 9.8 mg/L in juvenile Danio rerio, and 6.11 ± 2.48 mg/L in embryonic stages of Danio rerio. The study demonstrated a statistically higher sensitivity to diclofenac (P<0.05) in embryonic stages compared to the juvenile fish

Reaching for the stars : Iranian nurses\u27 perceptions of career success

Aim: The aim was to explore nurses\u27 perceptions of career success.Introduction: Career success is a concept which leads to improving professional behaviours. Research that focused on conceptualizing career success found it to be a complex, value-driven construct likely to be perceived differently across work and cultural contexts. It is not yet clear what constitutes career success, and how it is perceived by nurses in Iran. More comprehensive exploration of this concept in nursing is needed, so research and policymaking can advance in informed, data-driven manner.Method: This is a qualitative descriptive study. The setting was teaching hospitals of Iran. Twenty-seven nurses participated in face-to-face interviews, and six field notes were collected. Data were analysed using conventional content analysis.Findings: Analyses identified five themes of career success: providing high-quality care, being exemplary employee, embarking on career growth, having positive personal attributes and being internally satisfied.Conclusion: Findings confirmed that career success in Iranian nurses was a multidimensional concept that represented five internally and externally driven dimensions set within its cultural and religious context. Policymakers and clinical educators can now plan interventions aimed at fostering career success in nursing staff.Implications: Future nurses could use these finding to reflect on their developed attributes throughout their studies and clinical placements and adjust their career preparation and learning to bridge any identified gaps. Organizational values and intervention for nursing staff could also be redesigned to align with the aspects of career success

Self-Regulatory Processes Mediating Between Career Calling and Perceived Employability and Life Satisfaction in Emerging Adults

We tested a cross-sectional, mediation model of career calling, in which career calling was associated positively with life satisfaction and perceptions of future employability, and these relationships were explained by the self-regulatory mechanisms of work effort, career strategies, and emotional regulation. Using a sample of 664 emerging adults (74.8% female, mean age = 20.2 years) and structural equation modeling, we found that higher career calling was associated with higher life satisfaction and perceived employability. In addition, higher calling was associated with more work effort, greater use of career strategies, and higher emotional regulation. Work effort and emotional regulation mediated the relationship between career calling and life satisfaction. Additionally, work effort, emotional regulation, and career strategies mediated between career calling and perceived employability. We interpreted the results from a developmental and goal-setting perspective and made recommendations for practice.Griffith Health, School of Applied PsychologyFull Tex