Alunite and the role of magmatic fluids in the Tambo high-sulfidation deposit, El Indio–Pascua belt, Chile

The Tambo high-sulfidation deposit, located within the El Indio–Pascua belt in Chile, produced almost 25 t (0.8 M oz) of gold from altered Tertiary rhyodacitic volcanic rocks. Episodic magmatic-hydrothermal activity in the district occurred over at least 4 my and is characterized by several stages of acid-sulfate alteration, including magmatic-hydrothermal, magmatic steam, steam-heated, and apparent supergene assemblages. Two stages of Au±Ag mineralization are recognized and are hosted in barite and alunite within hydrothermal breccias and veins. Isotopic compositions of fluid in alunite show a dominant magmatic signature, with only a variable 18O-enriched meteoric water component throughout the entire hydrothermal process. Alunite 40Ar/39Ar ages constrain the timing of alteration and the duration of the hydrothermal system. Pre-ore alteration occurred at about 10 to 11 Ma and was contemporaneous with the volcanism of the Tambo Formation. Alunite from this stage of alteration occurs in the matrix of barren breccias and as fine intergrowths of alunite–quartz±clays that selectively replaced feldspars and pumice fragments. The textural relationships combined with stable-isotope systematics suggest a magmatic-hydrothermal origin for the alunite, with a local magmatic steam overprint. Early ore-stage alunite (8.7±0.2 Ma) occurs with barite and gold±walthierite within open spaces of the breccia matrix, and has δ34S values (24–27%◦) typical of magmatic-hydrothermal alunite, reflecting equilibrium between aqueous H2S and SO2 ̶ 4. Fluid-inclusion ratios of H2S/SO2 (approximately 6) are consistent with ratios determined from stable-isotope data, and indicate reduced fluid conditions during ore deposition. Vaporphase transport of Au, and deposition from condensed magmatic vapor rising from the brittle–ductile transition is inferred. Late gold coprecipitated with a third stage of alunite (8.2±0.2 Ma) that is characterized by nearly uniform chemical compositions and δ34S values (1%◦) similar to those for associated enargite, reflecting disequilibrium between H2S and SO2 ̶ 4. This third-stage of alunite is isotopically and chemically similar to that of post-ore, coarse, banded alunite±hematite-quartz veins that crosscut the breccias in the Tambo area. Analyses of fluid-inclusion gas from alunite in these veins indicate high SO2 and disequilibrium CO2–CO–CH4–H2 species, consistent with a magmatic-steam origin. The gases are also depleted in He, and the late goldbearing alunite was probably precipitated from rapidly ascending SO2-rich vapors that were flashed from condensed magmati

A bifunctional platinum(II) antitumor agent that forms DNA adducts with affinity for the estrogen receptor

A strategy is described for the re-design of DNA damaging platinum(II) complexes to afford elevated toxicity towards cancer cells expressing the estrogen receptor (ER). Two platinum-based toxicants are described in which a DNA damaging warhead, [Pt(en)Cl[subscript 2]] (en, ethylenediamine), is tethered to either of two functional groups. The first agent, [6-(2-amino-ethylamino)-hexyl]-carbamic acid 2-[6-(7α-estra-1,3,5,(10)-triene)-hexylamino]-ethyl ester platinum(II) dichloride ((Est-en)PtCl[subscript 2]), terminates in a ligand for the ER. The second agent is a control compound lacking the steroid; this compound, N-[6-(2-amino-ethylamino)-hexyl]-benzamide platinum(II) dichloride ((Bz-en)PtCl[subscript 2])), terminates in a benzamide moiety, which lacks affinity for the ER. Using a competitive binding assay, Est-en had 28% relative binding affinity (RBA) for the ER as compared to 17β-estradiol. After covalent binding to a synthetic DNA duplex 16-mer, the compound retained its affinity for the ER; specificity of the binding event was demonstrated by the ability of free 17β-estradiol as a competitor to disrupt the DNA adduct-ER complex. The (Est-en)PtCl[subscript 2] compound showed higher toxicity against the ER positive ovarian cancer cell line CAOV3 than did the control compound. (Est-en)PtCl[subscript 2] was also more toxic to the ER positive breast cancer line, MCF-7, than to an ER negative line, MDA-MB231.National Institutes of Health (U.S.) (Grant CA08661)Life Sciences Research Foundatio

The role of the P2X7 receptor on bone loss in a mouse model of inflammation-mediated osteoporosis

In inflammatory autoimmune diseases, bone loss is frequent. In most cases, secondary osteoporosis is caused by treatment with systemic glucocorticoid. However, the pathogenesis behind the bone loss is presumed multifactorial. We aimed to elucidate the role of the P2X7 receptor on bone mineral density (BMD), microarchitecture, and bone strength in a standardized mouse model of inflammation-mediated osteoporosis (IMO). In total 146 mice completed our protocol, 70 wild type (WT) mice and 76 P2X7−/− (knockout, KO). BMD at the femur and spine decreased significantly from baseline to day 20 in the WT IMO mice (p < 0.01). In the WT vehicle, KO vehicle and KO IMO, no significant BMD changes were found. Bone strength showed a lower mid-shaft max strength (p = 0.038) and also a non-significant trend towards lower strength at the femoral neck of the WT IMO group. Trabecular bone volume fraction (BV/TV) and connectivity density (CD) after 20 days were significantly decreased in the WT IMO group (p = 0.001). In contrast, the WT vehicle and KO vehicle, BV/TV and CD did no change at 20 days. Cortical bone revealed no significant microarchitectural changes after 20 days in the WT IMO group, whereas the total cortical area increased significantly in WT vehicle and KO IMO after 20 days (5.2% and 8.8%, respectively). In conclusion, the P2X7 receptor KO mice did not respond to inflammation with loss of BMD whereas the WT mice had a significant loss of BMD, bone strength and trabecular microarchitecture, demonstrating a role for the P2X7 receptor in inflammatory bone loss

Microbial sulfate reduction and metal attenuation in pH 4 acid mine water

Sediments recovered from the flooded mine workings of the Penn Mine, a Cu-Zn mine abandoned since the early 1960s, were cultured for anaerobic bacteria over a range of pH (4.0 to 7.5). The molecular biology of sediments and cultures was studied to determine whether sulfate-reducing bacteria (SRB) were active in moderately acidic conditions present in the underground mine workings. Here we document multiple, independent analyses and show evidence that sulfate reduction and associated metal attenuation are occurring in the pH-4 mine environment. Waterchemistry analyses of the mine water reveal: (1) preferential complexation and precipitation by H2S of Cu and Cd, relative to Zn; (2) stable isotope ratios of 34S/32S and 18O/16O in dissolved SO4 that are 2–3 ‰ heavier in the mine water, relative to those in surface waters; (3) reduction/oxidation conditions and dissolved gas concentrations consistent with conditions to support anaerobic processes such as sulfate reduction. Scanning electron microscope (SEM) analyses of sediment show 1.5-micrometer, spherical ZnS precipitates. Phospholipid fatty acid (PLFA) and denaturing gradient gel electrophoresis (DGGE) analyses of Penn Mine sediment show a high biomass level with a moderately diverse community structure composed primarily of iron- and sulfate-reducing bacteria. Cultures of sediment from the mine produced dissolved sulfide at pH values near 7 and near 4, forming precipitates of either iron sulfide or elemental sulfur. DGGE coupled with sequence and phylogenetic analysis of 16S rDNA gene segments showed populations of Desulfosporosinus and Desulfitobacterium in Penn Mine sediment and laboratory cultures

Changes in Outdoor Workers' Sun-Related Attitudes, Beliefs, and Behaviors: A Pre–Post Workplace Intervention

Objective: To evaluate changes in outdoor workers' sun-related attitudes, beliefs, and behaviors in response to a health promotion intervention using a participatory action research process. Methods: Fourteen workplaces across four outdoor industry types worked collaboratively with the project team to develop tailored sun protection action plans. Workers were assessed before and after the 18-month intervention. Results: Outdoor workers reported increases in workplace support for sun protection (P < 0.01) and personal use of sun protection (P < 0.01). More workers reported seeking natural shade (+20%) and wearing more personal protective equipment, including broad-brimmed hats (+25%), long-sleeved collared shirts (+19%), and long trousers (+16%). The proportion of workers reporting sunburn over the past 12 months was lower at postintervention (-14%) (P = 0.03); however, the intensity of reported sunburn increased. Conclusions: This intervention was successful in increasing workers' sun protective attitudes, beliefs, and behaviors

High EMSY expression defines a BRCA‐like subgroup of high‐grade serous ovarian carcinoma with prolonged survival and hypersensitivity to platinum

Background Approximately half of high‐grade serous ovarian carcinomas (HGSOCs) demonstrate homologous recombination repair (HR) pathway defects, resulting in a distinct clinical phenotype comprising hypersensitivity to platinum, superior clinical outcome, and greater sensitivity to poly(adenosine diphosphate‐ribose) polymerase (PARP) inhibitors. EMSY, which is known to be amplified in breast and ovarian cancers, encodes a protein reported to bind and inactivate BRCA2. Thus, EMSY overexpression may mimic BRCA2 mutation, resulting in HR deficiency. However, to our knowledge, the phenotypic consequences of EMSY overexpression in HGSOC patients has not been explored. Methods Here we investigate the impact of EMSY expression on clinical outcome and sensitivity to platinum‐based chemotherapy using available data from transcriptomically characterized HGSOC cohorts. Results High EMSY expression was associated with better clinical outcome in a cohort of 265 patients with HGSOC from Edinburgh (overall survival multivariable hazard ratio, 0.58 [95% CI, 0.38‐0.88; P = .011] and progression‐free survival multivariable hazard ratio, 0.62 [95% CI, 0.40‐0.96; P = .030]). Superior outcome also was demonstrated in the Medical Research Council ICON7 clinical trial and multiple publicly available data sets. Patients within the Edinburgh cohort who had high EMSY expression were found to demonstrate greater rates of complete response to multiple platinum‐containing chemotherapy regimens (radiological complete response rate of 44.4% vs 12.5% at second exposure; P = .035) and corresponding prolonged time to disease progression (median, 151.5 days vs 60.5 days after third platinum exposure; P = .004). Conclusions Patients with HGSOCs demonstrating high EMSY expression appear to experience prolonged survival and greater platinum sensitivity, reminiscent of BRCA‐mutant cases. These data are consistent with the notion that EMSY overexpression may render HGSOCs HR deficient

Sonar-induced pressure fields in a post-mortem common dolphin

Author Posting. © Acoustical Society of America, 2012. This article is posted here by permission of Acoustical Society of America for personal use, not for redistribution. The definitive version was published in Journal of the Acoustical Society of America 131 (2012): 1595-1604, doi:10.1121/1.3675005.Potential physical effects of sonar transmissions on marine mammals were investigated by measuring pressure fields induced in a 119-kg, 211-cm-long, young adult male common dolphin (Delphinus delphis) cadaver. The specimen was instrumented with tourmaline acoustic pressure gauges used as receiving sensors. Gauge implantation near critical tissues was guided by intraoperative, high-resolution, computerized tomography (CT) scanning. Instrumented structures included the melon, nares, ear, thoracic wall, lungs, epaxial muscle, and lower abdomen. The specimen was suspended from a frame equipped with a standard 50.8-mm-diameter spherical transducer used as the acoustic source and additional receiving sensors to monitor the transmitted and external, scattered field. Following immersion, the transducer transmitted pulsed sinusoidal signals at 5, 7, and 10 kHz. Quantitative internal pressure fields are reported for all cases except those in which the gauge failed or no received signal was detected. A full necropsy was performed immediately after the experiment to examine instrumented areas and all major organs. No lesions attributable to acoustic transmissions were found, consistent with the low source level and source-receiver distances.Work supported by NOPP through ONR Grant No. N000140710992. Work at CSI additionally supported by ONR Grant No. N000140811231

Mind the gut:Genomic insights to population divergence and gut microbial composition of two marine keystone species

BACKGROUND: Deciphering the mechanisms governing population genetic divergence and local adaptation across heterogeneous environments is a central theme in marine ecology and conservation. While population divergence and ecological adaptive potential are classically viewed at the genetic level, it has recently been argued that their microbiomes may also contribute to population genetic divergence. We explored whether this might be plausible along the well-described environmental gradient of the Baltic Sea in two species of sand lance (Ammodytes tobianus and Hyperoplus lanceolatus). Specifically, we assessed both their population genetic and gut microbial composition variation and investigated not only which environmental parameters correlate with the observed variation, but whether host genome also correlates with microbiome variation. RESULTS: We found a clear genetic structure separating the high-salinity North Sea from the low-salinity Baltic Sea sand lances. The observed genetic divergence was not simply a function of isolation by distance, but correlated with environmental parameters, such as salinity, sea surface temperature, and, in the case of A. tobianus, possibly water microbiota. Furthermore, we detected two distinct genetic groups in Baltic A. tobianus that might represent sympatric spawning types. Investigation of possible drivers of gut microbiome composition variation revealed that host species identity was significantly correlated with the microbial community composition of the gut. A potential influence of host genetic factors on gut microbiome composition was further confirmed by the results of a constrained analysis of principal coordinates. The host genetic component was among the parameters that best explain observed variation in gut microbiome composition. CONCLUSIONS: Our findings have relevance for the population structure of two commercial species but also provide insights into potentially relevant genomic and microbial factors with regards to sand lance adaptation across the North Sea-Baltic Sea environmental gradient. Furthermore, our findings support the hypothesis that host genetics may play a role in regulating the gut microbiome at both the interspecific and intraspecific levels. As sequencing costs continue to drop, we anticipate that future studies that include full genome and microbiome sequencing will be able to explore the full relationship and its potential adaptive implications for these species

Biochemical and structural studies of a L-haloacid dehalogenase from the thermophilic archaeon Sulfolobus tokodaii

addresses: Henry Wellcome Building for Biocatalysis, School of Biosciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK.types: Journal Article; Research Support, Non-U.S. Gov'tThis a post-print, author-produced version of an article accepted for publication in Extremophiles. Copyright © 2009 Springer Verlag. The definitive version is available at http://link.springer.com/article/10.1007%2Fs00792-008-0208-0Haloacid dehalogenases have potential applications in the pharmaceutical and fine chemical industry as well as in the remediation of contaminated land. The L: -2-haloacid dehalogenase from the thermophilic archaeon Sulfolobus tokodaii has been cloned and over-expressed in Escherichia coli and successfully purified to homogeneity. Here we report the structure of the recombinant dehalogenase solved by molecular replacement in two different crystal forms. The enzyme is a homodimer with each monomer being composed of a core-domain of a beta-sheet bundle surrounded by alpha-helices and an alpha-helical sub-domain. This fold is similar to previously solved mesophilic L: -haloacid dehalogenase structures. The monoclinic crystal form contains a putative inhibitor L: -lactate in the active site. The enzyme displays haloacid dehalogenase activity towards carboxylic acids with the halide attached at the C2 position with the highest activity towards chloropropionic acid. The enzyme is thermostable with maximum activity at 60 degrees C and a half-life of over 1 h at 70 degrees C. The enzyme is relatively stable to solvents with 25% activity lost when incubated for 1 h in 20% v/v DMSO