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

Long-Lasting Efficacy of Radio Electric Asymmetric Conveyer Neuromodulation Treatment on Functional Dysmetria, an Adaptive Motor Behavior

BackgroundFluctuating asymmetry (FA) is widely defined as the deviation from perfect bilateral symmetry and is considered an epigenetic measure of environmental stress. Rinaldi and Fontani hypothesized that the FA morpho-functional changes originate from an adaptive motor behavior determined by functional alterations in the cerebellum and neural circuits, not caused by a lesion, but induced by environmental stress. They called this phenomenon functional dysmetria (FD). On this premise, they developed the radio electric asymmetric conveyer (REAC) technology, a neuromodulation technology aimed at optimizing the best neuro-psycho-motor strategies in relation to environmental interaction.AimsPrevious studies showed that specific REAC neuro postural optimization (NPO) treatment can induce stable FD recovery. This study aimed to verify the duration of the NPO effect in inducing the stable FD recovery over timeMaterials and methodsData were retrospectively collected from a population of 29,794 subjects who underwent a specific semiological FD assessment and received the NPO treatment, regardless of the pathology referred.ResultsThe analysis of the data collected by the various participants in the study led us to ascertain the disappearance of FD in 100% of the cases treated, with a stability of the result detected up to 18 years after the single administration of the REAC NPO treatment.ConclusionsThe REAC NPO neurobiological modulation treatment consisting of a single administration surprisingly maintains a very long efficacy in the correction of FD. This effect can be explained as the long-lasting capacity of the NPO treatment to induce greater functional efficiency of the brain dynamics as proven in previous studies