Yacimiento cerro Vanguardia, Santa Cruz

El yacimiento se encuentra ubicado a unos 110 km., en línea recta, al noroeste de Puerto de San Julián. Un punto aproximadamente centrado en el área de campamento y planta tiene como coordenadas 48º23'28" L.S. y 68º15'51" L.O. El campamento minero se halla en las inmediaciones del que antiguamente fuera el casco de la estancia Cerro Vanguardia y a 4 km al noreste del cerro que da nombre al área. La altura promedio del área es del orden de 200 m s.n.m., con un máximo de 359 m s.n.m. en el cerro Vanguardia. El relieve es suave y ondulado. El avenamiento local se encauza por cortos arroyos de carácter efímero con escurrimiento hacia numerosas pequeñas cuencas centrípetas. Un camino enripiado, perfectamente mantenido, de 42 km, une el yacimiento con la Ruta Nacional 3 (35 km al sur del paraje Tres Cerros), constituyéndose en la principal vía de acceso.Instituto de Geología y Recursos MineralesInstituto de Recursos Minerale

Depósitos polimetálicos (tipo VMS) en la Cordillera Fueguina, Tierra del Fuego

El área se localiza entre los 54°30’ y 55° de latitud sur y 67°30’ y 68°40’de longitud oeste, en ámbito de la Cordillera Fueguina. Las manifestaciones se distribuyen en las sierras de Sorondo y Alvear. Los datos que se aportan en esta presentación se restringen a manifestaciones dentro del territorio argentino, desde la frontera con Chile al oeste, el lago Fagnano por el norte, hasta el canal de Beagle.Instituto de Recursos Minerale

Provincia auroargentífera del Deseado, Santa Cruz

El Macizo del Deseado, provincia de Santa Cruz, es una de las regiones que más ha avanzado en los últimos años en el conocimiento de sus características geológicas y metalogénicas, especialmente en aquellos sectores donde se emplazan depósitos epitermales auríferos de baja sulfuración. El descubrimiento a fin de la década del 70 (Genini, 1977 y 1990) y la posterior exploración y puesta en marcha en los 90 del yacimiento auroargentífero de Cerro Vanguardia, representa el ejemplo más conspicuo de un ya numeroso conjunto de áreas mineralizadas con metales preciosos, asociadas espacialmente por lo general al evento geológico más importante y extendido de la región: el volcanismo ácido jurásico del Grupo Bahía Laura. Además de Cerro Vanguardia, se pueden citar los prospectos de Manantial Espejo (con reservas medidas), La Josefina, (Schalamuk et al., 1995, 1997), Martinetas, Microondas, Lejano, Bacon, Cerro Saavedra, entre otros, que se hallan en exploración avanzada.Instituto de Recursos MineralesComisión de Investigaciones Científicas de la provincia de Buenos Aire

Multifaceted roles of the lipid scramblase TMEM16F in tauopathy

TMEM16F is a calcium-activated phospholipid scramblase and non-selective ion channel, which can move lipids bidirectionally across the plasma membrane. While earliest studies of TMEM16F have implicated its function in the release of microvesicles, large extracellular vesicles budded directly from the plasma membrane, we have found that knockout of TMEM16F from microglia additionally results in increased release of exosomes, extracellular vesicles derived from exocytosis of multivesicular bodies. Microglial exosomes have been implicated in the spread of soluble tau oligomers in the P301S mouse model of tauopathy. We sought to investigate the pathological effect of increased microglial exosomes from TMEM16F knockout in these tauopathy mice. When TMEM16F was removed from microglia, we observed worsening of hyperphosphorylated tau and microgliosis, suggesting an increase in exosomes can contribute towards pathology. However, when TMEM16F was knocked out from all cells, we found the opposite phenotype, with knockout mice having a reduction in pathology compared to those with TMEM16F intact. In P301S mice, neurons have been shown to aberrantly expose phosphatidylserine (PS), targeting them for premature death by microglia. Thus, we investigated if neurons with pathological tau burden and removal of TMEM16F still experienced this PS exposure and whether a deficiency in PS exposure may explain the reduction in pathology. In vitro cultures of tau burdened TMEM16F knockout neurons exposed less PS and had fewer interactions with WT microglia that were added to the neuronal cultures. These findings suggest TMEM16F may become activated in neurons with tauopathy to expose PS while TMEM16F in microglia may influence the balance of microvesicle and exosome release. Better understanding of TMEM16F may facilitate its manipulation in various cell types toward future development of therapeutics

Multifaceted roles of the lipid scramblase TMEM16F in tauopathy

TMEM16F is a calcium-activated phospholipid scramblase and non-selective ion channel, which can move lipids bidirectionally across the plasma membrane. While earliest studies of TMEM16F have implicated its function in the release of microvesicles, large extracellular vesicles budded directly from the plasma membrane, we have found that knockout of TMEM16F from microglia additionally results in increased release of exosomes, extracellular vesicles derived from exocytosis of multivesicular bodies. Microglial exosomes have been implicated in the spread of soluble tau oligomers in the P301S mouse model of tauopathy. We sought to investigate the pathological effect of increased microglial exosomes from TMEM16F knockout in these tauopathy mice. When TMEM16F was removed from microglia, we observed worsening of hyperphosphorylated tau and microgliosis, suggesting an increase in exosomes can contribute towards pathology. However, when TMEM16F was knocked out from all cells, we found the opposite phenotype, with knockout mice having a reduction in pathology compared to those with TMEM16F intact. In P301S mice, neurons have been shown to aberrantly expose phosphatidylserine (PS), targeting them for premature death by microglia. Thus, we investigated if neurons with pathological tau burden and removal of TMEM16F still experienced this PS exposure and whether a deficiency in PS exposure may explain the reduction in pathology. In vitro cultures of tau burdened TMEM16F knockout neurons exposed less PS and had fewer interactions with WT microglia that were added to the neuronal cultures. These findings suggest TMEM16F may become activated in neurons with tauopathy to expose PS while TMEM16F in microglia may influence the balance of microvesicle and exosome release. Better understanding of TMEM16F may facilitate its manipulation in various cell types toward future development of therapeutics

TMEM16F exacerbates tau pathology and mediates phosphatidylserine exposure in phospho-tau-burdened neurons.

TMEM16F is a calcium-activated phospholipid scramblase and nonselective ion channel, which allows the movement of lipids bidirectionally across the plasma membrane. While the functions of TMEM16F have been extensively characterized in multiple cell types, the role of TMEM16F in the central nervous system remains largely unknown. Here, we sought to study how TMEM16F in the brain may be involved in neurodegeneration. Using a mouse model that expresses the pathological P301S human tau (PS19 mouse), we found reduced tauopathy and microgliosis in 6- to 7-mo-old PS19 mice lacking TMEM16F. Furthermore, this reduction of pathology can be recapitulated in the PS19 mice with TMEM16F removed from neurons, while removal of TMEM16F from microglia of PS19 mice did not significantly impact tauopathy at this time point. Moreover, TMEM16F mediated aberrant phosphatidylserine exposure in neurons with phospho-tau burden. These studies raise the prospect of targeting TMEM16F in neurons as a potential treatment of neurodegeneration

Phosphatidylinositol-(4, 5)-bisphosphate regulates calcium gating of small-conductance cation channel TMEM16F.

TMEM16F, which is activated by elevation of intracellular calcium to trigger phospholipid scrambling and the collapse of lipid bilayer asymmetry to mediate important cellular functions such as blood coagulation, also generates a small-conductance calcium-activated cation current. How TMEM16F activation may be regulated is an open question. By recording TMEM16F Ca2+-activated current, we found that the TMEM16F Ca2+-response is desensitized by a brief exposure to high intracellular Ca2+, which is associated with depletion of phosphatidylinositol-(4, 5)-bisphosphate (PIP2) from the inner leaflet of the membrane. Application of artificial or natural PIP2 restores TMEM16F channel activity. PIP2 modulation of TMEM16F requires the presence of several positively charged amino acids in its cytoplasmic N-terminal domain. TMEM16F interaction with PIP2 works synergistically with membrane depolarization to facilitate Ca2+-gating of TMEM16F. Our study reveals the dependence of TMEM16F activity on phosphoinositides and provides one mechanism for TMEM16F activation to be strictly regulated in the cell membrane

Phosphatidylinositol-(4, 5)-bisphosphate regulates calcium gating of small-conductance cation channel TMEM16F

TMEM16F, which is activated by elevation of intracellular calcium to trigger phospholipid scrambling and the collapse of lipid bilayer asymmetry to mediate important cellular functions such as blood coagulation, also generates a small-conductance calcium-activated cation current. How TMEM16F activation may be regulated is an open question. By recording TMEM16F Ca2+-activated current, we found that the TMEM16F Ca2+-response is desensitized by a brief exposure to high intracellular Ca2+, which is associated with depletion of phosphatidylinositol-(4, 5)-bisphosphate (PIP2) from the inner leaflet of the membrane. Application of artificial or natural PIP2 restores TMEM16F channel activity. PIP2 modulation of TMEM16F requires the presence of several positively charged amino acids in its cytoplasmic N-terminal domain. TMEM16F interaction with PIP2 works synergistically with membrane depolarization to facilitate Ca2+-gating of TMEM16F. Our study reveals the dependence of TMEM16F activity on phosphoinositides and provides one mechanism for TMEM16F activation to be strictly regulated in the cell membrane