Absinthin, an agonist of the bitter taste receptor hTAS2R46, uncovers an ER-to-mitochondria Ca2–shuttling event

Type 2 taste receptors (TAS2R) are G protein-coupled receptors first described in the gustatory system, but have also been shown to have extra-oral localizations, including airway smooth muscle (ASM) cells, in which TAS2R have been reported to induce relaxation. TAS2R46 is an unexplored subtype that responds to its highly specific agonist absinthin. Here, we first demonstrate that, unlike other bitter-taste receptor agonists, absinthin alone (1 μM) in ASM cells does not induce Ca2+ signals, but reduces histamine-induced cytosolic Ca2+ increases. To investigate this mechanism, we introduced into ASM cells aequorin-based Ca2+ probes targeted to the cytosol, sub-plasma membrane domain, or the mitochondrial matrix. We show that absinthin reduces cytosolic histamine-induced Ca2+-rises and simultaneously increases Ca2+-influx into mitochondria. We found that this effect is inhibited by the potent human TAS2R46 (hTAS2R46) antagonist 3β-hydroxydihydrocostunolide and is no longer evident in hTAS2R46-silenced ASM cells, indicating that it is hTAS2R46-dependent. Furthermore, these changes were sensitive to the mitochondrial uncoupler carbonyl cyanide p-(trifluoromethoxy)phenyl-hydrazone (FCCP); the mitochondrial calcium uniporter inhibitor KB-R7943 (carbamimidothioic-acid); the cytoskeletal disrupter latrunculin; and an inhibitor of the exchange protein directly activated by cAMP (EPAC), ESI-09. Similarly, the β2 agonist salbutamol also could induce Ca2+ shuttling from cytoplasm to mitochondria, suggesting that this new mechanism might be generalizable. Moreover, forskolin and an EPAC activator mimicked this effect in HeLa cells. Our findings support the hypothesis that plasma membrane receptors can positively regulate mitochondrial Ca2+ uptake, adding a further facet to the ability of cells to encode complex Ca2+ signals

Liberalising Deployment of Internet of Things Devices and Services in Large Scale Environments

There is an ongoing enormous expansion of Internet of Things devices andservices in everyday life, notably in novel large scale urban environments called Smart Cities. There, availability and uses of Internet of Things by end users and businesses is mainly palpable subject to prior knowledge of the relevant providers and use of dedicated applications that are associated with them. This current reality can be largely ascribed to the property of ‘‘verticality’’ of autonomous Internet of Things eco-systems in Smart Cities, where Internet of Things devices (e.g. sensor nodes) are connected over a communicationinfrastructure to service-cloud platforms that deliver and process data that isthen presented at the applications level. This paper explains possibilities for revolutionary changes needed towards liberalising deployment and visibility of IoT services and data associated with them. It advocates a conceptual approach termed ‘‘horizontal networking for Internet of Things’’ facilitating a more open and generic presence of Internet of Things through the proposed Internet of Things identification meta-data. The vision is built on needed novel practical features in the current communication setups. The features comprise combinations of the opportunistic and near-match search and discovery model, Internet of Things identification meta-data also reflecting the physical and network-based dimensions of devices’ locations, novel routing and data flow models emerging via Information-Centric Networking and changes required in the elements of the current telecommunicationinfrastructure and the Internet

6lo Internet-Draft Intended status: Standards Track

IPv6 mapping to non-IP protocols draft-rizzo-6lo-6legacy-01 IPv6 is an important enabler of the Internet of Things, since it provides an addressing space large enough to encompass a vast and ubiquitous set of sensors and devices, allowing them to interconnect and interact seamlessly. To date, an important fraction of those devices is based on networking technologies other than IP. An important problem to solve in order to include them into an IPv6-based Internet of Things, is to define a mechanism for assigning an IPv6 address to each of them, in a way which avoids conflicts and protocol aliasing. The only existing proposal for such a mapping leaves many problems unsolved and it is nowadays inadequate to cope with the new scenarios which the Internet of Things presents. This document defines a mechanism, 6TONon-IP, for assigning automatically an IPv6 address to devices which do not support IPv6 or IPv4, in a way which minimizes the chances of address conflicts, and of frequent configuration changes due to instability of connection among devices. Such a mapping mechanism enables stateless autoconfiguration for legacy technology devices, allowing them to interconnect through the Internet and to fully integrate into a world wide scale, IPv6-based IoT