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

Il voucher sociale defiscalizzato nelle politiche di conciliazione lavoro-famiglia: valutazioni per l'Italia

none3Luca Beltrametti; Donatella Fresu; Alberto ZanardiBeltrametti, Luca; Donatella, Fresu; Alberto, Zanard

Il voucher sociale defiscalizzato nelle politiche di conciliazione lavoro-famiglia: valutazioni per l\u2019Italia

This paper analyzes the possible effects of the hypothetical introduction in Italy of a voucher program similar to the French CESU (Cheque Emploi Service Universel). After shortly discussing the rationale for public policies aimed at providing support to worklife balance, we introduce the possible role of vouchers in financing demand for such services. We remark that the CESU (together with similar programs currently run in the UK and in Belgium) set a new paradigm for social policy: the public financing takes the form of fiscal allowances and public funds are available under the condition that private money is spent on specific merit goods/services. We use a micro-simulation model in order to assess the impact of this program on family and firm budgets and on public finances in Italy. We find that these effects are substantial and that in the Italian tax system (where the role of tax expenditures with social aims is already large) the issue of tax allowance exhaustion is crucial

Il voucher sociale defiscalizzato nelle politiche di conciliazione lavoro-famiglia: valutazioni per l’Italia

This paper analyzes the possible effects of the hypothetical introduction in Italy of a voucher program similar to the French CESU (Cheque Emploi Service Universel). After shortly discussing the rationale for public policies aimed at providing support to worklife balance, we introduce the possible role of vouchers in financing demand for such services. We remark that the CESU (together with similar programs currently run in the UK and in Belgium) set a new paradigm for social policy: the public financing takes the form of tax allowances and public funds are available under the condition that private money is spent on specific merit goods/services. We use a micro-simulation model in order to assess the impact of this program on family and firm budgets and on public finances in Italy. We find that these effects are substantial and that in the Italian tax system the issue of tax allowance exhaustion is crucial

Macrophage polarization guided by immunomodulatory hydrogels

Hydrogels are among the most common biomaterials used for regenerative medicine applications. Amongst the important properties needed by hydrogels for their effective use in regenerative medicine, immunomodulation has sparked interest in researchers. This refers to the ability of the material to control the immune system upon implantation and drive it toward a favorable response, thus avoiding chronic inflammation and promoting functional tissue regeneration. In this context, modulating macrophage polarization proves to be a powerful immunomodulatory tool, by inducing the switch of macrophage phenotype from the classic inflammatory M1 phenotype or the antiinflammatory M2 phenotype. This chapter provides an overview of the current immunomodulatory hydrogels from natural and synthetic origins. The focus is on hydrogels able to modulate macrophage polarization towards the antiinflammatory M2 phenotype, either by loading them with immunomodulatory therapeutics or by exploiting their intrinsic immunomodulatory properties. Different examples of immunomodulatory hydrogels from different origins are provided. © 2024 Elsevier Inc. All rights reserved