Description: A subseafloor replacement-style barite and sulfide occurrence was drilled in shallow waters at the Palinuro volcanic complex, the northernmost Aeolian arc volcano in the Tyrrhenian Sea, Italy. Using a lander-type drilling device, 11 successful drill holes yielded a total of 13.5 m of core from a sediment-filled depression located at a water depth of 630 to 650 m. The longest continuous drill core recovered consists of 4.84 m of massive to semimassive barite and sulfides with abundant late, native sulfur overprint. Seafloor observations suggest that the hydrothermal system associated with the formation of the subseafloor barite and sulfide ore zone is still active, although black smoker activity does not occur on the seafloor. The recovered drill core shows that the subseafloor deposit is zoned with depth. The top of the mineralized zone is comprised of a variably silicified vuggy barite-sulfide facies that shows notable polymetallic metal enrichment, while the deeper portion of the mineralized zone is dominated by massive pyrite having distinctly lower base and precious metal grades. Metal zonation of the barite and sulfide deposit is related to the evolution of the hydrothermal fluids in space and time. The barite cap and the massive pyrite present in the deeper portion of the mineralized zone appear to have formed early in the paragenesis. During the main stage of the mineralization, the barite cap was brecciated and cemented by a polymetallic assemblage of barite and pyrite with minor chalcopyrite and tetrahedrite, trace famatinite, and rare cinnabar. Lower temperature precipitates formed during the main stage of mineralization include sphalerite, galena, pyrite, opal-A, and barite, which are associated with traces of Pb-Sb-As sulfosalts such as bournonite-seligmannite, or semseyite. A distinct mineral assemblage of fine-grained anhedral enargite, hypogene covellite, chalcopyrite, and galena is commonly associated with colloform sphalerite, galena, and pyrite as a late phase of this main stage. Colloform pyrite and marcasite are the last sulfides formed in the paragenetic sequence. The deposit is interpreted to have formed from fluids having an intermediate-sulfidation state, although excursions to high- and very high sulfidation states are indicated by the presence of abundant enargite and hypogene covellite. Laser ablation and conventional sulfur isotope analyses show that pyrite formed close to the seafloor within the zone of polymetallic metal enrichment has a variable sulfur isotope composition (δ34S = −39 to +3‰), whereas a more narrow range is observed in the massive pyrite at depth (δ34S = −10 to 0‰). Similar variations were also documented for the late native sulfur overprint. Overall, the negative sulfur isotope ratios at depth, the intermediate- to very high sulfidation conditions during mineralization, and the abundance of native sulfur suggest contributions of magmatic volatiles to the mineralizing fluids from a degassing magma chamber at depth. Biological processes are interpreted to have played a major role during late stages of ore formation. The combination of a subseafloor replacement deposit with a massive to semimassive barite cap rock overlying massive pyrite, the intermediate- to high-sulfidation characteristics, and the strong biological influence on the late stages of mineralization are distinct from other modern seafloor massive sulfide deposits and represents a style of submarine mineralization not previously recognized in a modern volcanic arc environment. The barite and sulfide occurrence at Palinuro shares many characteristics with porphyry-related base metal veins and intermediate-sulfidation epithermal deposits, suggesting that metallogenic processes associated with arc-related magmatic-hydrothermal systems are not restricted to the subaerial environment.

Description: Background Osteoporosis is a systemic skeletal disease characterised by reduced bone mineral density and increased susceptibility to fracture; these traits are highly heritable. Both common and rare copy number variants (CNVs) potentially affect the function of genes and may influence disease risk. Aim To identify CNVs associated with osteoporotic bone fracture risk. Method We performed a genome-wide CNV association study in 5178 individuals from a prospective cohort in the Netherlands, including 809 osteoporotic fracture cases, and performed in silico lookups and de novo genotyping to replicate in several independent studies. Results A rare (population prevalence 0.14%, 95% CI 0.03% to 0.24%) 210 kb deletion located on chromosome 6p25.1 was associated with the risk of fracture (OR 32.58, 95% CI 3.95 to 1488.89; p=8.69 x 10 –5 ). We performed an in silico meta-analysis in four studies with CNV microarray data and the association with fracture risk was replicated (OR 3.11, 95% CI 1.01 to 8.22; p=0.02). The prevalence of this deletion showed geographic diversity, being absent in additional samples from Australia, Canada, Poland, Iceland, Denmark, and Sweden, but present in the Netherlands (0.34%), Spain (0.33%), USA (0.23%), England (0.15%), Scotland (0.10%), and Ireland (0.06%), with insufficient evidence for association with fracture risk. Conclusions These results suggest that deletions in the 6p25.1 locus may predispose to higher risk of fracture in a subset of populations of European origin; larger and geographically restricted studies will be needed to confirm this regional association. This is a first step towards the evaluation of the role of rare CNVs in osteoporosis.

Description: Interferon lambda 4 protein can be generated in IFNL4 -G carriers but not IFNL4 -TT homozygotes. We studied 890 anti–hepatitis C virus (HCV)–positive participants in the Women's Interagency HIV Study. Among blacks (n = 555), HCV was more often cleared for those with genotype IFNL4 -TT/TT (32.6%; odds ratio [OR], 3.59; P = 3.3 x 10 –5 ) than IFNL4 -TT/G (11.3%; OR, 0.95; P = .86) or IFNL4 -G/G (11.9%; referent). Pooling these data with published results in blacks (n = 1678), ORs were 3.84 ( P = 8.6 x 10 –14 ) for IFNL4 -TT/TT and 1.44 ( P = .03) IFNL4 -TT/G, and the area under the curve was 0.64 for IFNL4 -G genotype and 0.61 for rs12979860 ( IL28B ). IFNL4 -G is strongly associated with impaired spontaneous HCV clearance.

Description: Bitter taste receptors (TAS2Rs) mediate aversive response to toxic food, which is often bitter. These G-protein-coupled receptors are also expressed in extraoral tissues, and emerge as novel targets for therapeutic indications such as asthma and infection. Our goal was to identify ligands of the broadly tuned TAS2R14 among clinical drugs. Molecular properties of known human bitter taste receptor TAS2R14 agonists were incorporated into pharmacophore- and shape-based models and used to computationally predict additional ligands. Predictions were tested by calcium imaging of TAS2R14-transfected HEK293 cells. In vitro testing of the virtual screening predictions resulted in 30–80% success rates, and 15 clinical drugs were found to activate the TAS2R14. hERG potassium channel, which is predominantly expressed in the heart, emerged as a common off-target of bitter drugs. Despite immense chemical diversity of known TAS2R14 ligands, novel ligands and previously unknown polypharmacology of drugs were unraveled by in vitro screening of computational predictions. This enables rational repurposing of traditional and standard drugs for bitter taste signaling modulation for therapeutic indications.—Levit, A., Nowak, S., Peters, M., Wiener, A., Meyerhof, W., Behrens, M., Niv, M. Y. The bitter pill: clinical drugs that activate the human bitter taste receptor TAS2R14.

Description: Achondrite meteorites have anomalous enrichments in 33S, relative to chondrites, which have been attributed to photochemistry in the solar nebula. However, the putative photochemical reactions remain elusive, and predicted accompanying 33S depletions have not previously been found, which could indicate an erroneous assumption regarding the origins of the 33S anomalies,...

Description: Author(s): J. A. Peters, M. Sebastian, S. Nguyen, Zhifu Liu, Jino Im, A. J. Freeman, M. G. Kanatzidis, and B. W. Wessels Native defect levels in ternary compound Tl6I4S single crystals were studied by low-temperature photoluminescence (PL) and photoconductivity (PC) measurements. From the PL measurements, a broad emission band centered at 1.64 eV was observed at low temperatures. The peak can be decomposed using two s... [Phys. Rev. B 90, 035205] Published Fri Jul 18, 2014

Description: A subseafloor replacement-style barite and sulfide occurrence was drilled in shallow waters at the Palinuro volcanic complex, the northernmost Aeolian arc volcano in the Tyrrhenian Sea, Italy. Using a lander-type drilling device, 11 successful drill holes yielded a total of 13.5 m of core from a sediment-filled depression located at a water depth of 630 to 650 m. The longest continuous drill core recovered consists of 4.84 m of massive to semimassive barite and sulfides with abundant late, native sulfur overprint. Seafloor observations suggest that the hydrothermal system associated with the formation of the subseafloor barite and sulfide ore zone is still active, although black smoker activity does not occur on the seafloor. The recovered drill core shows that the subseafloor deposit is zoned with depth. The top of the mineralized zone is comprised of a variably silicified vuggy barite-sulfide facies that shows notable polymetallic metal enrichment, while the deeper portion of the mineralized zone is dominated by massive pyrite having distinctly lower base and precious metal grades. Metal zonation of the barite and sulfide deposit is related to the evolution of the hydrothermal fluids in space and time. The barite cap and the massive pyrite present in the deeper portion of the mineralized zone appear to have formed early in the paragenesis. During the main stage of the mineralization, the barite cap was brecciated and cemented by a polymetallic assemblage of barite and pyrite with minor chalcopyrite and tetrahedrite, trace famatinite, and rare cinnabar. Lower temperature precipitates formed during the main stage of mineralization include sphalerite, galena, pyrite, opal-A, and barite, which are associated with traces of Pb-Sb-As sulfosalts such as bournonite-seligmannite, or semseyite. A distinct mineral assemblage of fine-grained anhedral enargite, hypogene covellite, chalcopyrite, and galena is commonly associated with colloform sphalerite, galena, and pyrite as a late phase of this main stage. Colloform pyrite and marcasite are the last sulfides formed in the paragenetic sequence. The deposit is interpreted to have formed from fluids having an intermediate-sulfidation state, although excursions to high- and very high sulfidation states are indicated by the presence of abundant enargite and hypogene covellite. Laser ablation and conventional sulfur isotope analyses show that pyrite formed close to the seafloor within the zone of polymetallic metal enrichment has a variable sulfur isotope composition ( 34 S = –39 to +3), whereas a more narrow range is observed in the massive pyrite at depth ( 34 S = –10 to 0). Similar variations were also documented for the late native sulfur overprint. Overall, the negative sulfur isotope ratios at depth, the intermediate- to very high sulfidation conditions during mineralization, and the abundance of native sulfur suggest contributions of magmatic volatiles to the mineralizing fluids from a degassing magma chamber at depth. Biological processes are interpreted to have played a major role during late stages of ore formation. The combination of a subseafloor replacement deposit with a massive to semimassive barite cap rock overlying massive pyrite, the intermediate- to high-sulfidation characteristics, and the strong biological influence on the late stages of mineralization are distinct from other modern seafloor massive sulfide deposits and represents a style of submarine mineralization not previously recognized in a modern volcanic arc environment. The barite and sulfide occurrence at Palinuro shares many characteristics with porphyry-related base metal veins and intermediate-sulfidation epithermal deposits, suggesting that metallogenic processes associated with arc-related magmatic-hydrothermal systems are not restricted to the subaerial environment.

Description: Reduced expression of SMN protein causes spinal muscular atrophy (SMA), a neurodegenerative disorder leading to motor neuron dysfunction and loss. However, the molecular mechanisms by which SMN regulates neuronal dysfunction are not fully understood. Here, we report that reduced SMN protein level alters miRNA expression and distribution in neurons. In particular, miR-183 levels are increased in neurites of SMN-deficient neurons. We demonstrate that miR-183 regulates translation of mTor via direct binding to its 3' UTR. Interestingly, local axonal translation of mTor is reduced in SMN-deficient neurons, and this can be recovered by miR-183 inhibition. Finally, inhibition of miR-183 expression in the spinal cord of an SMA mouse model prolongs survival and improves motor function of Smn -mutant mice. Together, these observations suggest that axonal miRNAs and the mTOR pathway are previously unidentified molecular mechanisms contributing to SMA pathology.