Production of interleukin-10 by alveolar macrophages from lung cancer patients

AbstractInterleukin (IL)-10 is known to be an autoregulatory factor of functions of monocyte macrophages. The purpose of this study was to determine whether IL-10 production by alveolar macrophages (AMs) is altered in patients with lung cancer. AMs were obtained by bronchoalveolar lavage from 25 patients with lung cancer and 14 control patients. The production of IL-10 by AMs was quantitated by enzyme immunoassay with or without stimulation with lipopolysaccharide (LPS). No significant difference in spontaneous and LPS-stimulated IL-10 production by AMs was observed between lung cancer patients and control patients (mean ± sem; 288·0 ± 56·7 vs. 249·6 ± 58·4 pg ml−1). IL-10 production of LPS-stimulated AMs was not impaired even in lung cancer patients with systemic metastasis. IL-4 failed to suppress LPS-induced production of IL-10 by AMs both in control patients and in lung cancer patients. In eight patients with lung cancer, IL-10 production by AMs was estimated before and after systemic chemotherapy and IL-10 production by LPS-stimulated AMs tended to increase after systemic chemotherapy from 152·3 ± 51·9 to 278·0 ± 112·8 pg ml−1. As IL-10 is a potent inhibitor of tumour angiogenesis, an important process of tumour progression, these results suggest that, even in advanced cancer patients, macrophages can produce potent angiogenesis inhibitor and systemic chemotherapy may augment this inhibitory activity in the lung

Large sulfur isotope fractionations in Martian sediments at Gale crater

Variability in the sulfur isotopic composition in sediments can reflect atmospheric, geologic and biological processes. Evidence for ancient fluvio-lacustrine environments at Gale crater on Mars and a lack of efficient crustal recycling mechanisms on the planet suggests a surface environment that was once warm enough to allow the presence of liquid water, at least for discrete periods of time, and implies a greenhouse effect that may have been influenced by sulfur-bearing volcanic gases. Here we report in situ analyses of the sulfur isotopic compositions of SO2 volatilized from ten sediment samples acquired by NASA’s Curiosity rover along a 13 km traverse of Gale crater. We find large variations in sulfur isotopic composition that exceed those measured for Martian meteorites and show both depletion and enrichment in 34S. Measured values of δ34S range from −47 ± 14‰ to 28 ± 7‰, similar to the range typical of terrestrial environments. Although limited geochronological constraints on the stratigraphy traversed by Curiosity are available, we propose that the observed sulfur isotopic signatures at Gale crater can be explained by equilibrium fractionation between sulfate and sulfide in an impact-driven hydrothermal system and atmospheric processing of sulfur-bearing gases during transient warm periods

Three-Dimensional Spatially Constrained Sulfur Isotopes Highlight Processes Controlling Sulfur Cycling in the Near Surface of the Iheya North Hydrothermal System, Okinawa Trough

Abstract Modern seafloor hydrothermal systems are unique environments in which many of the Earth's reservoirs, including the hydrosphere, biosphere, and geosphere, dynamically interact. Analysis of spatially constrained sulfur isotope compositions from fluids and hydrothermal precipitates within the discharge zone of a volcanogenic system can be used to trace the interactions between the various isotopically distinct sulfur reservoirs that result in the formation of hydrothermal massive sulfide deposits. Here we present in situ sulfur isotope results from laterally and vertically constrained euhedral hydrothermal pyrite from the Iheya North hydrothermal system in the Okinawa Trough, which was investigated during the Integrated Ocean Drilling Program Expedition 331. Hydrothermal pyrite at the North Big Chimney yields δ34S values of ~+11.9 ± 1.1‰ (1σ), which are near identical to the δ34S composition of the vent fluid. Outward, ~150 and ~450 m from North Big Chimney, hydrothermal pyrite within drill core yields δ34S equal to +10.9 ± 1.3‰ (1σ) and +7.0 ± 3.8‰ (1σ), respectively, showing a shift in isotopic composition away from the main vent site. This evolution to a lighter and more scattered isotopic signature of hydrothermal pyrite (which is easily identifiable from biogenic pyrite) is interpreted to indicate that the hydrothermal fluid leached sulfides (formed previously by biogenic processes) from the surrounding sedimentary strata. As the most significant metal enrichments (Fe, Zn, Cu, Bi, Tl, and Cd) are associated with samples that contain average hydrothermal pyrite δ34S values similar to δ34S of the vent fluid, we demonstrate that sulfur isotopes can vector toward metals in seafloor massive sulfide deposits

An Archean Biosphere Initiative

The search for life on extrasolar planets will necessarily focus on the imprints of biolgy on the composition of planetary atmospheres. The most notable biological imprint on the modern terrestrial atmosphere is the presence of 21 % O2, However, during most of the past 4 billion years, life and the surface environments on Earth were profoundly different than they are today. It is therefore a major goal of the astrobiology community to ascertain how the O2 content of the atmosphere has varied with time. and to understand the causes of these variations. The NAI and NASA Exobiology program have played critical roles in developing our current understanding of the ancient Earth's atmosphere, supporting diverse observational, analytical, and computational research in geoscience, life science, and related fields. In the present incarnation of the NAI, ongoing work is investigating (i) variations in atmospheric O2 in the Archean to the Cambrian, (ii) characterization of the redox state of the oceans shortly before, during and after the Great Oxidation Event (GOE), and (iii) unraveling the complex connections between environmental oxygenation, global climate, and the evolution of life

Transport of Pb and Zn by carboxylate complexes in basinal ore fluids and related petroleum-field brines at 100°C: the influence of pH and oxygen fugacity

It is well established through field observations, experiments, and chemical models that oxidation (redox) state and pH exert a strong influence on the speciation of dissolved components and the solubility of minerals in hydrothermal fluids. log [Image: see text] –pH diagrams were used to depict the influence of oxygen fugacity and pH on monocarboxylate- and dicarboxylate-transport of Pb and Zn in low-temperature (100°C) hydrothermal ore fluids that are related to diagenetic processes in deep sedimentary basins, and allow a first-order comparison of Pb and Zn transport among proposed model fluids for Mississippi Valley-type (MVT) and red-bed related base metal (RBRBM) deposits in terms of their approximate pH and [Image: see text] conditions. To construct these diagrams, total Pb and Zn concentrations and Pb and Zn speciation were calculated as a function of log [Image: see text] and pH for a composite ore-brine with concentrations of major elements, total sulfur, and total carbonate that approximate the composition of MVT and RBRBM model ore fluids and modern basinal brines. In addition to acetate and malonate complexation, complexes involving the ligands Cl(-), HS(-), H(2)S, and OH(- )were included in the model of calculated total metal concentration and metal speciation. Also, in the model, Zn and Pb are competing with the common-rock forming metals Ca, Mg, Na, Fe, and Al for the same ligands. Calculated total Pb concentration and calculated total Zn concentration are constrained by galena and sphalerite solubility, respectively. Isopleths, in log [Image: see text] –pH space, of the concentration of Pb and concentration of Zn in carboxylate (acetate + malonate) complexes illustrate that the oxidized model fluids of T. H. Giordano (in Organic Acids in Geological Processes, ed. E. D. Pittman and M. D. Lewan, Springer-Verlag, New York, 1994, pp. 319–354) and G. M. Anderson (Econ. Geol., 1975, 70, 937–942) are capable of transporting sufficient amounts of Pb (up to 10 ppm) and Zn (up to 100 ppm) in the form of carboxylate complexes to form economic deposits of these metals. On the other hand, the reduced ore fluid models of D. A. Sverjensky (Econ. Geol., 1984, 79, 23–37) and T. H. Giordano and H. L. Barnes (Econ. Geol., 1981, 76, 2200–2211) can at best transport amounts of Pb and Zn, as carboxylate complexes, that are many orders of magnitude below the 1 to 10 ppm minimum required to form economic deposits. Lead and zinc speciation (mol% of total Pb or Zn) in the model ore fluid was calculated at specific log [Image: see text] –pH conditions along the 100, 0.01, and 0.001 ppm total Pb and total Zn isopleths. Along the 100 ppm isopleth conditions are oxidized (∑SO(4 )>> ∑H(2)S) with Pb and Zn predominantly in the form of chloride complexes under acid to mildly alkaline conditions (pH from 3 to approximately 7.5), while hydroxide complexes dominate Pb and Zn speciation under more alkaline conditions. Sulfide complexes are insignificant under these oxidized conditions. For more reduced conditions along the 0.01 and 0.001 ppm isopleths chloride complexes dominate Pb and Zn speciation in the SO(4)(2- )field and near the SO(4)(2-)-reduced sulfur boundary from pH = 4 to approximately 7.5, while hydroxide complexes dominate Pb and Zn speciation under alkaline conditions above pH = 7.5 in the SO(4)(2- )field. In the most reduced fluids (∑H(2)S >> ∑SO(4)) along the 0.01 and 0.001 isopleths, sulfide complexes account for almost 100% of the Pb and Zn in the model fluid. Acetate (monocarboxylate) complexation is significant only under conditions of chloride and hydroxide complex dominance and its effect is maximized in the pH range 5 to 7, where it complexes 2 to 2.6% of the total Pb and 1 to 1.25% of the total Zn. Malonate (dicarboxylate) complexes are insignificant along all isopleths. The speciation results from this study show that deep formation waters characterized by temperatures near 100°C, high oxidation states and ∑H(2)S < 0.03 mg L(-1 )([Image: see text] < 10(-6)), high chlorinities (~ 100000 mg L(-1)), and high but reasonable concentrations of carboxylate anions can mobilize up to 3% of the total Pb and up to 1.3% of the total Zn as carboxylate complexes. Furthermore, these percentages, under the most favorable conditions, correspond to approximately 1 to 100 ppm of these metals in solution; concentrations that are adequate to form economic deposits of these metals. However, the field evidence suggests that all of these optimum conditions for carboxylate complexation are rarely met at the same time. A comparison of the composite ore fluid compositions from this study and modern brine data shows that the ore brines, corresponding to log [Image: see text] –pH conditions based on the Anderson (1975) and Giordano (1994) model fluids, are similar in many respects to modern, high trace-metal petroleum-field brines. The principal differences between modern high trace-metal brines and the composite ore fluids of Anderson (1975) and Giordano (1994) relate to their carboxylate anion content. The reported concentrations of monocarboxylate anions (∑monocbx) and dicarboxylate anions (Edicbx) in high trace-metal petroleum-field brines (< 1 to 300 mg L(-1 )and < 1 mg L(-1), respectively) are significantly lower than the concentrations assumed in the modelled brines of this study (∑monocbx = 7 700 mg L(-1 )and ∑dicbx = 300 mg L(-1)). There are also major differences in the corresponding total chloride to carboxylate ratio (∑m(Cl)/∑m(cbx)) and monocarboxylate to dicarboxylate ratio (∑m(monocbx)/∑m(dicbx)). Modern high trace-metal brines have much higher ∑m(Cl)/∑m(cbx )values and, therefore, the contribution of carboxylate complexes to the total Pb and Zn content in these modern brines is likely to be significantly less than the 1 to 3 percent for the composite ore fluids of Anderson (1975) and Giordano (1994). The composite ore-brine based on the Giordano and Barnes (1981) MVT ore fluid is comparable to the high salinity (> 170 000 mg L(-1 )TDS) subset of modern brines characterized by low trace-metal content and high total reduced sulfur (∑H(2)S). A comparison of the Sverjensky (1984) composite ore-brine with modern petroleum-field brines in terms of ∑H(2)S and Zn content, reveals that this ore fluid corresponds to a "border-type" brine, between modern high trace-metal brines and those with low trace-metal content and high ∑H(2)S. A brine of this type is characterized by values of ∑H(2)S, ∑Zn, and/or ∑Pb within or near the 1 to 10 mg L(-1 )range. Based on brine-composition data from numerous references cited in this paper, border-type brines do exist but are rare. The model results and field evidence presented in this study are consistent with other chemical simulation studies of carboxylate complexation in modern petroleum-field brines. Thus, it appears that carboxylate complexation plays a minor, if not insignificant, role as a transport mechanism for Pb and Zn in high salinity Na–Cl and Na–Ca–Cl basinal brines and related ore fluids

CALHM3 Is Essential for Rapid Ion Channel-Mediated Purinergic Neurotransmission of GPCR-Mediated Tastes

Binding of sweet, umami, and bitter tastants to G protein-coupled receptors (GPCRs) in apical membranes of type II taste bud cells (TBCs) triggers action potentials that activate a voltage-gated nonselective ion channel to release ATP to gustatory nerves mediating taste perception. Although calcium homeostasis modulator 1 (CALHM1) is necessary for ATP release, the molecular identification of the channel complex that provides the conductive ATP-release mechanism suitable for action potential-dependent neurotransmission remains to be determined. Here we show that CALHM3 interacts with CALHM1 as a pore-forming subunit in a CALHM1/CALHM3 hexameric channel, endowing it with fast voltage-activated gating identical to that of the ATP-release channel in vivo. Calhm3 is co-expressed with Calhm1 exclusively in type II TBCs, and its genetic deletion abolishes taste-evoked ATP release from taste buds and GPCR-mediated taste perception. Thus, CALHM3, together with CALHM1, is essential to form the fast voltage-gated ATP-release channel in type II TBCs required for GPCR-mediated tastes. Ma et al. identify a CALHM1/CALHM3 hetero-hexameric ion channel as the mechanism by which type II taste bud cells release ATP as a neurotransmitter to gustatory neurons in response to GPCR-mediated tastes, including sweet, bitter, and umami substances. © 2018 Elsevier Inc

Search for Chargino-Neutralino Associated Production at the Fermilab Tevatron Collider

We have searched in $p \bar{p}$ collisions at $\sqrt{s}$ = 1.8 TeV for events with three charged leptons and missing transverse energy. In the Minimal Supersymmetric Standard Model, we expect trilepton events from chargino-neutralino (\chione \chitwo) pair production, with subsequent decay into leptons. We observe no candidate $e^+e^-e^\pm$, $e^+e^-\mu^\pm$, $e^\pm\mu^+\mu^-$ or $\mu^+\mu^-\mu^\pm$ events in 106 pb$^{-1}$ integrated luminosity. We present limits on the sum of the branching ratios times cross section for the four channels: \sigma_{\chione\chitwo}\cdot BR(\chione\chitwo\to 3\ell+X) 81.5 \mgev\sp and M_\chitwo > 82.2 \mgev\sp for $\tan\beta=2$, $\mu =-600$~\mgev\sp and M_\squark= M_\gluino.Comment: 9 pages and 3 figure

Constraining the fluid history of a CO2 -H2 S reservoir: insights from stable isotopes, REE and fluid inclusion microthermometry

Reservoirs that host CO2‐H2S‐bearing gases provide a key insight into crustal redox reactions such as thermochemical sulfate reduction (TSR). Despite this, there remains a poor understanding of the extent, duration, and the factors limiting this process on a reservoir scale. Here we show how a combination of petrography, fluid inclusion, rare earth element (REE), and carbon (δ13C), oxygen (δ18O), and sulfur (δ34S) stable isotope data can disentangle the fluid history of the world's largest CO2 accumulation, the LaBarge Field in Wyoming, USA. The carbonate‐hosted LaBarge Field was charged with oil around 80 Ma ago, which together with nodular anhydrite represent the reactants for TSR. The nodules exhibit two distinct trends of evolution in δ13C with both δ34S and δ18O that may be coupled to two different processes. The first trend was interpreted to reflect the coupled dissolution of anhydrite and reduction to elemental sulfur and the oxidation of organic compounds and associated precipitation of calcite during TSR. In contrast, the second trend was interpreted to be the result of the hydrothermal CO2 influx after the cessation of TSR. In addition, mass balance calculations were performed to estimate an approximate TSR reaction duration of 80 ka and to identify the availability of organic compounds as the limiting factor of the TSR process. Such an approach provides a tool for the prediction of TSR occurrence elsewhere and advancing our understanding of crustal fluid interactions

Observation of Hadronic W Decays in t-tbar Events with the Collider Detector at Fermilab

We observe hadronic W decays in t-tbar -> W (-> l nu) + >= 4 jet events using a 109 pb-1 data sample of p-pbar collisions at sqrt{s} = 1.8 TeV collected with the Collider Detector at Fermilab (CDF). A peak in the dijet invariant mass distribution is obtained that is consistent with W decay and inconsistent with the background prediction by 3.3 standard deviations. From this peak we measure the W mass to be 77.2 +- 4.6 (stat+syst) GeV/c^2. This result demonstrates the presence of two W bosons in t-tbar candidates in the W (-> l nu) + >= 4 jet channel.Comment: 20 pages, 4 figures, submitted to PR

Search for charged Higgs decays of the top quark using hadronic tau decays

We present the result of a search for charged Higgs decays of the top quark, produced in $p\bar{p}$ collisions at $\surd s =$ 1.8 TeV. When the charged Higgs is heavy and decays to a tau lepton, which subsequently decays hadronically, the resulting events have a unique signature: large missing transverse energy and the low-charged-multiplicity tau. Data collected in the period 1992-1993 at the Collider Detector at Fermilab, corresponding to 18.7$\pm$0.7~pb$^{-1}$, exclude new regions of combined top quark and charged Higgs mass, in extensions to the standard model with two Higgs doublets.Comment: uuencoded, gzipped tar file of LaTeX and 6 Postscript figures; 11 pp; submitted to Phys. Rev.