Advanced argillic alteration at Cave di Caolino, Lipari, Aeolian Islands (Italy): Implications for the mitigation of volcanic risks and the exploitation of geothermal resources.

Four sites in the western sector of Lipari Island with still active hydrothermal activity are here considered. The petrography (mesoscopic observations and XRPD) and geochemistry (major, minor and trace elements chemistry) of ten representative and extremely altered volcanic rocks were characterized. Two types of parageneses of altered rocks are discriminable, one rich in silicate phases (opal/cristobalite, montmorillonite, kaolinite, alunite and hematite) and one in sulphates (gypsum, plus minor amounts of anhydrite or bassanite). The altered silicate-rich rocks are rich in SiO2, Al2O3, Fe2O3 and H2O, and depleted in CaO, MgO, K2O and Na2O, while the sulphate-rich ones are extremely enriched in CaO and SO4 in comparison with local unaltered volcanic rocks. The content of many incompatible elements is similar in altered silicate-rich rocks and lower in sulphate-rich ones with respect to the pristine volcanic rocks; conversely, almost all REEs are markedly enriched in silicate-rich rocks and heavy REEs are enriched in sulphate-rich altered rocks compared to unaltered volcanic rocks. Reaction path modelling of basaltic andesite dissolution in local steam condensate predicts the production of amorphous-silica, anhydrite, goethite, and kaolinite (or smectites and saponites) as stable secondary minerals and alunite, jarosite, and jurbanite as ephemeral minerals. Considering possible post-depositional reactions and admitting that the presence of two distinct parageneses is apparent, since gypsum is prone to form large crystals, it can be concluded that there is an excellent agreement between the alteration minerals occurring in nature and those predicted by geochemical modelling. Consequently, the modelled process is the main responsible for the production of the advanced argillic alteration assemblage of "Cave di Caolino" on Lipari Island. Since rock alteration is sustained by the H2SO4 solution produced by hydrothermal steam condensation, there is no need to invoke the involvement of SO2-HCl-HF-bearing magmatic fluids, in line with the absence of fluoride minerals.

mTORC1 hyperactivation arrests bone growth in lysosomal storage disorders by suppressing autophagy.

The mammalian target of rapamycin complex 1 (mTORC1) kinase promotes cell growth by activating biosynthetic pathways and suppressing catabolic pathways, particularly that of macroautophagy. A prerequisite for mTORC1 activation is its translocation to the lysosomal surface. Deregulation of mTORC1 has been associated with the pathogenesis of several diseases, but its role in skeletal disorders is largely unknown. Here, we show that enhanced mTORC1 signaling arrests bone growth in lysosomal storage disorders (LSDs). We found that lysosomal dysfunction induces a constitutive lysosomal association and consequent activation of mTORC1 in chondrocytes, the cells devoted to bone elongation. mTORC1 hyperphosphorylates the protein UV radiation resistance-associated gene (UVRAG), reducing the activity of the associated Beclin 1-Vps34 complex and thereby inhibiting phosphoinositide production. Limiting phosphoinositide production leads to a blockage of the autophagy flux in LSD chondrocytes. As a consequence, LSD chondrocytes fail to properly secrete collagens, the main components of the cartilage extracellular matrix. In mouse models of LSD, normalization of mTORC1 signaling or stimulation of the Beclin 1-Vps34-UVRAG complex rescued the autophagy flux, restored collagen levels in cartilage, and ameliorated the bone phenotype. Taken together, these data unveil a role for mTORC1 and autophagy in the pathogenesis of skeletal disorders and suggest potential therapeutic approaches for the treatment of LSDs.