TRPV6 Determines the Effect of Vitamin D3 on Prostate Cancer Cell Growth

Despite remarkable advances in the therapy and prevention of prostate cancer it is still the second cause of death from cancer in industrialized countries. Many therapies initially shown to be beneficial for the patients were abandoned due to the high drug resistance and the evolution rate of the tumors. One of the prospective therapeutical agents even used in the first stage clinical trials, 1,25-dihydroxyvitamin D3, was shown to be either unpredictable or inefficient in many cases. We have already shown that TRPV6 calcium channel, which is the direct target of 1,25-dihydroxyvitamin D3 receptor, positively controls prostate cancer proliferation and apoptosis resistance (Lehen'kyi et al., Oncogene, 2007). However, how the known 1,25-dihydroxyvitamin D3 antiproliferative effects may be compatible with the upregulation of pro-oncogenic TRPV6 channel remains a mystery. Here we demonstrate that in low steroid conditions 1,25-dihydroxyvitamin D3 upregulates the expression of TRPV6, enchances the proliferation by increasing the number of cells entering into S-phase. We show that these pro-proliferative effects of 1,25-dihydroxyvitamin D3 are directly mediated via the overexpression of TRPV6 channel which increases calcium uptake into LNCaP cells. The apoptosis resistance of androgen-dependent LNCaP cells conferred by TRPV6 channel is drastically inversed when 1,25-dihydroxyvitamin D3 effects were combined with the successful TRPV6 knockdown. In addition, the use of androgen-deficient DU-145 and androgen-insensitive LNCaP C4-2 cell lines allowed to suggest that the ability of 1,25-dihydroxyvitamin D3 to induce the expression of TRPV6 channel is a crucial determinant of the success or failure of 1,25-dihydroxyvitamin D3-based therapies

Social Aspects of CSCL Environments: A Research Framework

Although there are research findings supporting the positive effects of computer-supported col- laborative learning (CSCL), problems have been reported regarding the learning process itself, group formation, and group dynamics. These problems can be traced back to impeded social interaction between group members. Social interaction is necessary (a) for group members to learn from each other in a CSCL environment and (b) for socioemotional processes to help cre- ate a social space where trust, sense of community, and strong interpersonal relationships exist. This article introduces a theoretical framework consisting of three core elements: sociability, social space, and social presence, along with their relationships with group members’ mental models, social affordances and learning outcomes. It postulates that the three core elements influence the social interaction needed for both learning and the emergence of a social space. This framework serves as a basis for a research agenda for systematic social CSCL research

The evolving field of tangible interaction for children : the challenge of empirical validation

This special issue is devoted to the topic of tangible user interfaces and children. It emphasizes research on tangibility that transcends system descriptions, focusing on the empirical support of theories and design guidance. The papers result from the organization of a workshop at the CHI 2009 ACM conference in Boston, USA. As an introduction to this issue, empirical evidence is discussed for the potential benefits that using TUIs may have for children. In particular, we focus at the impact of tangibility in terms of usability, learning, collaboration and fun. Finally, we suggest directions for future work and outline the papers that are included in this special issue

Numerical study of elemental demixing in atmospheric entry flow regimes near local thermodynamic equilibrium

We apply a recently derived and explicitly closed form of the equations of chemically reacting flows under local thermodynamic equilibrium to investigate its applicability to hypersonic flows. This new model rigorously takes into account the effects of the separation of chemical elements due to the differential diffusion of species, known as elemental demixing. We study the particular case of a neutral 5-species air flow around a blunt body configuration, with realistic free stream conditions corresponding to the later stages of a re-entry trajectory of a future space mission. In order to assess to what extent the local equilibrium assumption holds for the consider physical problem, we compare our results with other ones obtained using a chemical non-equilibrium model. Particular attention is paid to the distribution of oxygen elements in the flow field