In vitro bioassay investigations of the endocrine disrupting potential of steviol glycosides and their metabolite steviol, components of the natural sweetener Stevia

The food industry is moving towards the use of natural sweeteners such as those produced by Stevia rebaudiana due to the number of health and safety concerns surrounding artificial sweeteners. Despite the fact that these sweeteners are natural; they cannot be assumed safe. Steviol glycosides have a steroidal structure and therefore may have the potential to act as an endocrine disruptor in the body. Reporter gene assays (RGAs), H295R steroidogenesis assay and Ca(2+) fluorimetry based assays using human sperm cells have been used to assess the endocrine disrupting potential of two steviol glycosides: stevioside and rebaudioside A, and their metabolite steviol. A decrease in transcriptional activity of the progestagen receptor was seen following treatment with 25,000 ng/ml steviol in the presence of progesterone (157 ng/ml) resulting in a 31% decrease in progestagen response (p=<0.01). At the level of steroidogenesis, the metabolite steviol (500-25,000 ng/ml) increased progesterone production significantly by 2.3 fold when exposed to 10,000 ng/ml (p=<0.05) and 5 fold when exposed to 25,000 ng/ml (p=<0.001). Additionally, steviol was found to induce an agonistic response on CatSper, a progesterone receptor of sperm, causing a rapid influx of Ca(2+). The response was fully inhibited using a specific CatSper inhibitor. These findings highlight the potential for steviol to act as a potential endocrine disruptor.

Effect of the Knowledge Representation Form on the Efficiency of Knowledge Sharing

The goal of this thesis is to estimate the effect of the form of knowledge representation on the efficiency of knowledge sharing. The objectives include the design of an experimental framework which would allow to establish this effect, data collection, and statistical analysis of the collected data. The study follows the experimental quantitative design. The experimental questionnaire features three sample forms of knowledge: text, mind maps, concept maps. In the interview, these forms are presented to an interviewee, afterwards the knowledge sharing time and knowledge sharing quality are measured. According to the statistical analysis of 76 interviews, text performs worse in both knowledge sharing time and quality compared to visualized forms of knowledge representation. However, mind maps and concept maps do not differ in knowledge sharing time and quality, since this difference is not statistically significant. Since visualized structured forms of knowledge perform better than unstructured text in knowledge sharing, it is advised for companies to foster the usage of these forms in knowledge sharing processes inside the company. Aside of performance in knowledge sharing, the visualized structured forms are preferable due the possibility of their usage in the system of ontological knowledge management within an enterprise.

Our future in geriatrics : an examination of the knowledge, attitudes and career choices of physical therapy students in Ontario : a pretest-posttest study /

There continues to be a shortage of health professionals interested in providing care for the older adult. Part of the problem seems to stem from the negative perceptions of geriatrics as a clinical speciality. This study examines the knowledge, attitudes and career decisions of physical therapy students in Ontario before and after an educational intervention. Surveys were conducted with 144 physical therapy students from five universities before and after their geriatrics course in order to measure their knowledge, attitudes and interest in working with older adults. The incoming class of physical therapy students (n = 1 86) acted as control subjects for the study. The Revised Palmore Facts On Aging Quiz measured the students' knowledge of aging (Miller & Dodder, 1980). The Revised Tuckman-Lorge (Axelrod & Eisdorfer, 1961) and the Kogan Old People Scales (Kogan, 1961) were used to examine attitude. An environmental scale was developed based on the work of Snape (1986) to measure the impact of the working conditions on the students' career choices. A 10-point Likert-type scale based on the work of Michlelutte & Diseker (1985) was modified and used to measure career interest in working with the elderly. On independent sample t-tests, positive attitudes were related to the demographic characteristic of gender; ethnicity was negatively related; and marital status was found to be unrelated to attitude (fi<.05). Having a relationship with an older adult and taking courses in gerontology were also found to be positively related to attitude (fi<.05). Results on a betweensubjects design which compared students before and after the course found that knowledge scores improved from pretest to posttest (fi<.05). In general, attitude scores improved from T1 to T2 on both measurement tools (b<.05). The environmental and vocational interest scales yielded statistically significant differences between the control and experimental groups during the intervention period (p<.05). The results of this research indicated that knowledge and attitudes improve after an educational intervention; however, there was little impact on the students' overall career decisions. Further research is indicated to examine the complex relationship between attitude and behaviour and its impact on students' career choices. In addition, the impact of geriatric clinical environment on students' attitudes and career decisions needs to be further explored.

M & A cases : definition of the relevant market.

Rapport de recherche

Unveiling the components of the signaling pathway between endosomes and the phagocytic uptake machinery in Dictyostelium discoideum

The soil amoebae Dictyostelium discoideum take up particles from their environment in order to obtain nutrition. The particle transits through the cell within a phagosome that fuses with organelles of different molecular compositions, undergoing a gradual degradation by different sets of hydrolytic enzymes. Griffiths’ concept of “phagosome individuality” predicts signaling from phagosomes into the cytoplasm, which might regulate many aspects of cell physiology. The finding that Dictyostelium cells depleted of the lysozyme AlyA or over-expressing the esterase Gp70 exhibit increased uptake of food particles, led to the postulation of a signaling cascade between endocytic compartments and the cytoskeletal uptake machinery at the plasma membrane. Assuming that Gp70 acts downstream of AlyA, gene-expression profiling of both mutants revealed different and overlapping sets of misregulated genes that might participate in this signaling cascade. Based on these results, we analyzed the effects of the artificial misregulation of six candidate genes by over-expression or negative genetic interference, in order to reconstruct at least part of the signaling pathway. SSB420 and SSL793 were chosen as candidates for the first signaling step, as they were up-regulated in AlyA-null cells and remained unaltered in the Gp70 over-expressing cells. The over-expression of SSB420 enhanced phagocytosis and raised the expression levels of Gp70, supporting its involvement in the signaling pathway between AlyA and Gp70 as a positive regulator of phagocytosis. However, this was not the case of cells over-expressing SSL793, as this mutation had no effects on phagocytosis. For the signaling downstream of Gp70, we studied four commonly misregulated genes in AlyA-depleted and Gp70 over-expressing cells. The expression levels of SLB350, SSB389 and TipD were lower in both mutants and therefore these were assumed as possible candidates for the negative regulation of phagocytosis. Cells depleted of SLB350 exhibited an increased phagocytic activity and no effect on Gp70 expression, proving its participation in the signaling pathway downstream of Gp70. Unlike SLB350, the disruption of the genes coding for SSB389 and TipD had no effects on particle uptake, excluding them from the pathway. The fourth candidate was Yipf1, the only gene that was commonly up-regulated in both mutants. Yet, the artificial over-expression of this protein had no effects on phagocytosis, so this candidate is also not included in the signaling pathway. Furthermore, localizing the products of the candidate genes within the cell helped unveiling several cellular organelles that receive signals from the phagosome and transduce them towards the uptake machinery.