Functional role of cell surface CUB domain-containing protein 1 in tumour cell dissemination

The function of CUB domain-containing protein 1 (CDCP1), a recently described transmembrane protein expressed on the surface of hematopoietic stem cells and normal and malignant cells of different tissue origin, is not well defined. The contribution of CDCP1 to tumor metastasis was analyzed by using HeLa carcinoma cells overexpressing CDCP1 (HeLa-CDCP1) and a high-disseminating variant of prostate carcinoma PC-3 naturally expressing high levels of CDCP1 (PC3-hi/diss). CDCP1 expression rendered HeLa cells more aggressive in experimental metastasis in immunodeficient mice. Metastatic colonization by HeLa-CDCP1 was effectively inhibited with subtractive immunization-generated, CDCP1-specific monoclonal antibody (mAb) 41-2, suggesting that CDCP1 facilitates relatively late stages of the metastatic cascade. In the chick embryo model, time- and dose-dependent inhibition of HeLa-CDCP1 colonization by mAb 41-2 was analyzed quantitatively to determine when and where CDCP1 functions during metastasis. Quantitative PCR and immunohistochemical analyses indicated that CDCP1 facilitated tumor cell survival soon after vascular arrest. Live cell imaging showed that the function-blocking mechanism of mAb 41-2 involved enhancement of tumor cell apoptosis, confirmed by attenuation of mAb 41-2–mediated effects with the caspase inhibitor z-VAD-fmk. Under proapoptotic conditions in vitro, CDCP1 expression conferred HeLa-CDCP1 cells with resistance to doxorubicin-induced apoptosis, whereas ligation of CDCP1 with mAb 41-2 caused additional enhancement of the apoptotic response. The functional role of naturally expressed CDCP1 was shown by mAb 41-2–mediated inhibition of both experimental and spontaneous metastasis of PC3-hi/diss. These findings confirm that CDCP1 functions as an antiapoptotic molecule and indicate that during metastasis CDCP1 facilitates tumor cell survival likely during or soon after extravasation.

Regular exercise participation mediates the affective response to acute bouts of vigorous exercise

Physical inactivity is a leading factor associated with cardiovascular disease and a major contributor to the global burden of disease in developed countries. Subjective mood states associated with acute exercise are likely to influence future exercise adherence and warrant further investigation. The present study examined the effects of a single bout of vigorous exercise on mood and anxiety between individuals with substantially different exercise participation histories. Mood and anxiety were assessed one day before an exercise test (baseline), 5 minutes before (pre-test) and again 10 and 25 minutes post-exercise. Participants were 31 university students (16 males, 15 females; Age M = 20), with 16 participants reporting a history of regular exercise with the remaining 15 reporting to not exercise regularly. Each participant completed an incremental exercise test on a Monark cycle ergometer to volitional exhaustion. Regular exercisers reported significant post-exercise improvements in mood and reductions in state anxiety. By contrast, non-regular exercisers reported an initial decline in post-exercise mood and increased anxiety, followed by an improvement in mood and reduction in anxiety back to pre-exercise levels. Our findings suggest that previous exercise participation mediates affective responses to acute bouts of vigorous exercise. We suggest that to maximise positive mood changes following exercise, practitioners should carefully consider the individual’s exercise participation history before prescribing new regimes.

Diffusion of corporate governance practices : the Dutch response to pressures for shareholder value

As part of a larger literature focused on identifying and relating the antecedents and consequences of diffusing organizational practices/ideas, recent research has debated the international adoption of a shareholder-value-orientation (SVO). The debate has financial economists characterizing the adoption of an SVO as performance-enhancing and thus inevitable, with behavioral scientists disputing both claims, invoking institutional differences. This study seeks to provide some resolution to the debate (and advance current understanding on the diffusion of practices/ideas) by developing a socio-political perspective that links the antecedents and consequences of an SVO. In particular, we introduce the notion of misaligned elites and misfitted practices in our analysis of how and why differences in the technical and cultural preferences of major owners will influence a firm’s adoption and (un)successful implementation of an SVO among the largest 100 corporations in the Netherlands from 1992-2006. We conclude with a discussion of the implications of our perspective and our findings for future research on corporate governance and the diffusion of organizational practices/ideas.

Response : letter to the editor by Al-Azri and Al-Maniri

Firstly, the authors would like to thank the editor for the opportunity to respond to Dr Al-Azri’s and Dr Al-Maniri’s letter. Secondly, while the current authors also accept that deterrence-based approaches should act as only one corner-stone of a suite of interventions and public policy initiatives designed to improve road safety, deterrence-based approaches have nonetheless consistently proven to be a valuable resource to improve road safety. Dr Al-Azri and Dr Al-Maniri reinforce their assertion about the limited utility of deterrence by citing drink driving research, and the issue of drink driving is particularly relevant within the current context given that the problem of driving after drinking has historically been addressed through deterrence-based approaches. While the effectiveness of deterrence-based approaches to reduce drink driving will always be dependent upon a range of situational and contextual factors (including police enforcement practices, cultural norms, etc), the utilisation of this approach has proven particularly effective within Queensland, Australia. For example, a relatively recent comprehensive review of Random Breath Testing in Queensland demonstrated that this initiative not only had a deterrent impact upon self-reported intentions to drink and drive, but was also found to have significantly reduced alcohol-related fatalities in the state. However, the authors agree that deterrence-based approaches can be particularly transient and thus require constant “topping up” not least through sustained public reinforcement, which was clearly articulated in the seminal work by Homel.

Replication of the Frank-Starling response in a Mock Circulation loop

Mock circulation loops (MCLs) are used to evaluate cardiovascular devices prior to in-vivo trials; however they lack the vital autoregulatory responses that occur in humans. This study aimed to develop and implement a left and right ventricular Frank-Starling response in a MCL. A proportional controller based on ventricular end diastolic volume was used to control the driving pressure of the MCL’s pneumatically operated ventricles. Ventricular pressure-volume loops and end systolic pressure-volume relationships were produced for a variety of healthy and pathological conditions and compared with human data to validate the simulated Frank-Starling response. The non-linear Frank-Starling response produced in this study successfully altered left and right ventricular contractility with changing preload and was validated with previously reported data. This improvement to an already detailed MCL has resulted in a test rig capable of further refining cardiovascular devices and reducing the number of in-vivo trials.