Does Work Affect Personality? A Study in Horses

It has been repeatedly hypothesized that job characteristics are related to changes in personality in humans, but often personality models still omit effects of life experience. Demonstrating reciprocal relationships between personality and work remains a challenge though, as in humans, many other influential factors may interfere. This study investigates this relationship by comparing the emotional reactivity of horses that differed only by their type of work. Horses are remarkable animal models to investigate this question as they share with humans working activities and their potential difficulties, such as “interpersonal” conflicts or “suppressed emotions”. An earlier study showed that different types of work could be associated with different chronic behavioural disorders. Here, we hypothesised that type of work would affect horses' personality. Therefore over one hundred adult horses, differing only by their work characteristics were presented standardised behavioural tests. Subjects lived under the same conditions (same housing, same food), were of the same sex (geldings), and mostly one of two breeds, and had not been genetically selected for their current type of work. This is to our knowledge the first time that a direct relationship between type of work and personality traits has been investigated. Our results show that horses from different types of work differ not as much in their overall emotional levels as in the ways they express emotions (i.e. behavioural profile). Extremes were dressage horses, which presented the highest excitation components, and voltige horses, which were the quietest. The horses' type of work was decided by the stall managers, mostly on their jumping abilities, but unconscious choice based on individual behavioural characteristics cannot be totally excluded. Further research would require manipulating type of work. Our results nevertheless agree with reports on humans and suggest that more attention should be given to work characteristics when evaluating personalities

Consistency and flexibility in solving spatial tasks: different horses show different cognitive styles

Individual animals vary in their behaviour and reactions to novel situations. These differences may extend to differences in cognition among individuals. We tested twenty-six horses for their ability to detour around symmetric and asymmetric obstacles. All of the animals were able to get around the barrier to reach a food target, but varied in their approach. Some horses moved slowly but were more accurate in choosing the shortest way. Other horses acted quickly, consistently detoured in the same direction, and did not reliably choose the shortest way. The remaining horses shifted from a faster, directionally consistent response with the symmetric barrier, to a slower but more accurate response with the asymmetric barrier. The asymmetric barrier induced a reduction in heart rate variability, suggesting that this is a more demanding task. The different approaches used to solve the asymmetric task may reflect distinct cognitive styles in horses, which vary among individuals, and could be linked to different personality traits. Understanding equine behaviour and cognition can inform horse welfare and management

Field template-based design and biological evaluation of new sphingosine kinase 1 inhibitors

Purpose: Sphingosine kinase 1 (SK1) is a protooncogenic enzyme expressed in many human tumours and is associated with chemoresistance and poor prognosis. It is a potent therapy target and its inhibition chemosensitises solid tumours. Despite recent advances in SK1 inhibitors synthesis and validation, their clinical safety and chemosensitising options are not well described. In this study, we have designed, synthesised and tested a new specific SK1 inhibitor with a low toxicity profile. Methods: Field template molecular modelling was used for compound design. Lead compounds were tested in cell and mouse cancer models. Results: Field template analysis of three known SK1 inhibitors, SKI-178, 12aa and SK1-I, was performed and compound screening identified six potential new SK1 inhibitors. SK1 activity assays in both cell-free and in vitro settings showed that two compounds were effective SK1 inhibitors. Compound SK-F has potently decreased cancer cell viability in vitro and sensitised mouse breast tumours to docetaxel (DTX) in vivo, without significant whole-body toxicity. Conclusion: Through field template screening, we have identified a new SK1 inhibitor, SK-F, which demonstrated antitumour activity in vitro and in vivo without overt toxicity when combined with DTX

Enhanced expression of transferrin receptor 1 contributes to oncogenic signalling by sphingosine kinase 1

Advance online publication 25 November 2013Sphingosine kinase 1 (SK1) is a lipid kinase that catalyses the formation of sphingosine-1-phosphate (S1P). Considerable evidence has implicated elevated cellular SK1 in tumour development, progression and disease severity. In particular, SK1 has been shown to enhance cell survival and proliferation and induce neoplastic transformation. Although S1P has been found to have both cell-surface G-protein-coupled receptors and intracellular targets, the specific downstream pathways mediating oncogenic signalling by SK1 remain poorly defined. Here, using a gene expression array approach, we have demonstrated a novel mechanism whereby SK1 regulates cell survival, proliferation and neoplastic transformation through enhancing expression of transferrin receptor 1 (TFR1). We showed that elevated levels of SK1 enhanced total as well as cell-surface TFR1 expression, resulting in increased transferrin uptake into cells. Notably, we also found that SK1 activation and localization to the plasma membrane, which are critical for its oncogenic effects, are necessary for regulation of TFR1 expression specifically through engagement of the S1P G-protein coupled receptor, S1P2. Furthermore, we showed that blocking TFR1 function with a neutralizing antibody inhibits SK1-induced cell proliferation, survival and neoplastic transformation of NIH3T3 fibroblasts. Similar effects were observed following antagonism of S1P2. Together these findings suggest that TFR1 has an important role in SK1-mediated oncogenesis.D H Pham, J A Powell, B L Gliddon, P A B Moretti, A Tsykin, M Van der Hoek, R Kenyon, G J Goodall and S M Pitso