Modulation of Ca2+ entry by polypeptides of the inositol 1,4,5-trisphosphate receptor (IP3R) that bind transient receptor potential (TRP): Evidence for roles of TRP and IP3R in store depletion-activated Ca2+ entry

Homologues of Drosophilia transient receptor potential (TRP) have been proposed to be unitary subunits of plasma membrane ion channels that are activated as a consequence of active or passive depletion of Ca2+ stores. In agreement with this hypothesis, cells expressing TRPs display novel Ca2+-permeable cation channels that can be activated by the inositol 1,4,5-trisphosphate receptor (IP3R) protein. Expression of TRPs alters cells in many ways, including up-regulation of IP3Rs not coded for by TRP genes, and proof that TRP forms channels of these and other cells is still missing. Here, we document physical interaction of TRP and IP3R by coimmunoprecipitation and glutathione S-transferase-pulldown experiments and identify two regions of IP3R, F2q and F2g, that interact with one region of TRP, C7. These interacting regions were expressed in cells with an unmodified complement of TRPs and IP3Rs to study their effect on agonist- as well as store depletion-induced Ca2+ entry and to test for a role of their respective binding partners in Ca2+ entry. C7 and an F2q-containing fragment of IP3R decreased both forms of Ca2+ entry. In contrast, F2g enhanced the two forms of Ca2+ entry. We conclude that store depletion-activated Ca2+ entry occurs through channels that have TRPs as one of their normal structural components, and that these channels are directly activated by IP3Rs. IP3Rs, therefore, have the dual role of releasing Ca2+ from stores and activating Ca2+ influx in response to either increasing IP3 or decreasing luminal Ca2+.

SMEs and Level 2 BIM, the Way Forward

The UK construction industry comprises a very high proportion of SMEs that is companies employing up to 250. A Department for Business, Innovation and Skills research paper, found that SMEs had a 71.2% share of work in the construction industry. Micro and small firms (i.e. those employing up to 50) had a share of 46.7% of work (Ive and Murray 2013). The Government has high ambitions for UK construction. Having been found by successive government commissioned studies to be inefficient and highly fragmented, ambitious targets have been set for the industry to achieve 33% reduction in costs and 50% faster delivery by 2025. As a significant construction client, the Government has mandated the use of Level 2 BIM from 2016 on publicly funded projects over £5 million. The adoption of BIM plays a key role in the 2025 vision but a lack of clarity persists in the industry over BIM and significant barriers are perceived to its implementation, particularly amongst SMEs. However, industry wide transformation will be challenging without serious consideration of the capabilities of this large majority. Many larger firms, having implemented Level 2 BIM are now working towards Level 3 BIM while many of the smaller firms in the industry have not even heard of BIM. It would seem that fears of a ‘two tier’ industry are perhaps being realised. This paper builds on an earlier one (Mellon & Kouider 2014) and investigates, through field work, the level of Level 2 BIM implementation amongst SMEs compared to a large organisation. Challenges and innovative solutions identified through collected data are fully discussed and compared. It is suggested that where the SME perceives barriers towards adoption of the technologies which underpin BIM, they may consider collaborative methods of working as an interim step in order to work towards realising the efficiencies and benefits that these methods can yield. While the barriers to adoption of BIM are significant, it is suggested that they are not insurmountable for the SME and some recommendations for possible solutions are made.

Youth Sports: Implementing Findings and Moving Forward with Research

This paper reviews the literature, outlines practical implications, and discusses future studies in youth sport researc h. The literature is discussed in light of three potential benefits of youth sport participation 1) physic al health, 2) psycho- social development, and 3) motor skills acquisition. The ultimate objective of youth sport programs is to consider all the benefits of youth sport participation rather than focusing on one or two at the cost of the other(s). It is suggested that researchers, s port administrators, coaches, and parents work together to promote sporting activities and programs that are more likely to enhance children’s physical health, psychosocia l development and lifelong recreational or elite sport participation.

Chain-store system of marketing and distribution.

Mode of access: Internet.