Pathogenesis of prostate cancer and hormone refractory prostate cancer

Prostate cancer is the second most common malignancy in males and the leading cause of cancer death. Prostate cancer is initially androgen dependent and relies upon the androgen receptor (AR) to mediate the effects of androgens. The AR is also the target for therapy using antiandrogens and LHRH analogues. However, all cancers eventually become androgen independent, often referred to as hormone refractory prostate cancer. The processes involved in this transformation are yet to be fully understood but research in this area has discovered numerous potential mechanisms including AR amplification, over-expression or mutation and alterations in the AR signaling pathway. This review of the recent literature examines the current knowledge and developments in the understanding of the molecular biology of prostate cancer and hormone refractory prostate cancer, summarizing the well characterized pathways involved as well as introducing new concepts that may offer future solutions to this difficult problem.

TRP Channels and calcium signalling in dental pulp stem cells

Introduction: Ca2+ ion is an important intracellular messenger essential for the regulation of various cellular functions including proliferation, differentiation and apoptosis. Transient Receptor Potential (TRP) channels are calcium permeable cationic channels that play important role in regulation of free intracellular calcium ([Ca2+]i) in response to thermal, physical and chemical stimuli. Ca2+ signalling in human dental pulp stem cells (hDPSCs) and the ion channels regulating Ca2+ are largely not known. Objectives: Investigate changes in [Ca2+]i and determine the ion channels that regulate calcium signalling in hDPSCs. Methods: DPSCs were derived from immature third molars and cells less than passage 6 were used in all the experiments. Changes in [Ca2+]i were studied with Fura2 calcium imaging. RNA was extracted from DPSCs and a panel of TRP channel gene expression was determined by qPCR employing custom designed FAM TRP specific primers and probes (Roche, UK) and the Light Cycler 480 Probes Master (Roche). Results: hDPSCs express gene transcripts for all TRP families including TRPV1, V2, V4, TRPA1, TRPC3, TRPC5, TRPC6, TRPM3, TRPM7 and TRPP2. Stimulation of cells with appropriate TRP channel agonist induced increase in [Ca2+]i and similar responses were obtained when cell were mechanically stimulated by membrane stretch with application of hypotonic solution. Conclusion: TRP channels mediate calcium signalling in hDPSCs that merit further investigation.

Perceptions of high-involvement work practices and burnout: the mediating role of job demands

This study examined the impact of perceived high-involvement work practices on job demands (role conflict, role overload and role ambiguity) and burnout (emotional exhaustion and depersonalisation). The study was conducted in a Canadian general hospital. Findings from structural equation modelling (N = 545) revealed that perceived HIWPs were significantly and negatively related to job demands and burnout. Role conflict and role overload have a significant positive association with emotional exhaustion and depersonalisation. Finally, role conflict and role overload partially mediate the relationship between perceived HIWPs and burnout. We discuss the theoretical and managerial implications of these findings for our understanding of how HIWPs influence the job demands and burnout of employees.

Adapting to time: duration channels do not mediate human time perception

Accurately encoding the duration and temporal order of events is essential for survival and important to everyday activities, from holding conversations to driving in fast flowing traffic. Although there is a growing body of evidence that the timing of brief events (< 1s) is encoded by modality-specific mechanisms, it is not clear how such mechanisms register event duration. One approach gaining traction is a channel-based model; this envisages narrowly-tuned, overlapping timing mechanisms that respond preferentially to different durations. The channel-based model predicts that adapting to a given event duration will result in overestimating and underestimating the duration of longer and shorter events, respectively. We tested the model by having observers judge the duration of a brief (600ms) visual test stimulus following adaptation to longer (860ms) and shorter (340ms) stimulus durations. The channel-based model predicts perceived duration compression of the test stimulus in the former condition and perceived duration expansion in the latter condition. Duration compression occurred in both conditions, suggesting that the channel-based model does not adequately account for perceived duration of visual events.