616 research outputs found

    Acid-sensing ion channel 3 decreases phosphorylation of extracellular signal-regulated kinases and induces synoviocyte cell death by increasing intracellular calcium.

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    IntroductionAcid-sensing ion channel 3 (ASIC3) is expressed in synoviocytes, activated by decreases in pH, and reduces inflammation in animal models of inflammatory arthritis. The purpose of the current study was to characterize potential mechanisms underlying the control of inflammation by ASIC3 in fibroblast-like synoviocytes (FLS).MethodsExperiments were performed in cultured FLS from wild-type (WT) and ASIC3-/- mice, ASIC1-/- mice, and people with rheumatoid arthritis. We assessed the effects of acidic pH with and without interleukin-1β on FLS and the role of ASICs in modulating intracellular calcium [Ca(2+)](i), mitogen activated kinase (MAP kinase) expression, and cell death. [Ca(2+)](i) was assessed by fluorescent calcium imaging, MAP kinases were measured by Western Blots; ASIC, cytokine and protease mRNA expression were measured by quantitative PCR and cell death was measured with a LIVE/DEAD assay.ResultsAcidic pH increased [Ca(2+)](i) and decreased p-ERK expression in WT FLS; these effects were significantly smaller in ASIC3-/- FLS and were prevented by blockade of [Ca(2+)]i. Blockade of protein phosphatase 2A (PP2A) prevented the pH-induced decreases in p-ERK. In WT FLS, IL-1β increases ASIC3 mRNA, and when combined with acidic pH enhances [Ca(2+)](i), p-ERK, IL-6 and metalloprotienase mRNA, and cell death. Inhibitors of [Ca(2+)](i) and ERK prevented cell death induced by pH 6.0 in combination with IL-1β in WT FLS.ConclusionsDecreased pH activates ASIC3 resulting in increased [Ca(2+)](i), and decreased p-ERK. Under inflammatory conditions, acidic pH results in enhanced [Ca(2+)](i) and phosphorylation of extracellular signal-regulated kinase that leads to cell death. Thus, activation of ASIC3 on FLS by acidic pH from an inflamed joint could limit synovial proliferation resulting in reduced accumulation of inflammatory mediators and subsequent joint damage

    LiGaSe2 optical parametric oscillator pumped by a Q-switched Nd:YAG laser

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    Optical parametric oscillation is demonstrated for the first time with the chalcogenide nonlinear crystal LiGaSe2 pumped by a nanosecond Nd:YAG laser. Angle tuning provides coverage of the 4.8–9.9 μm spectral range in the mid-IR by idler pulses

    Accurate spectroscopy of Sr atoms

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    We report the frequency measurement with an accuracy in the 100 kHz range of several optical transitions of atomic Sr : 1S03P1^1S_0- ^3P_1 at 689 nm, 3P13S1^3P_1- ^3S_1 at 688 nm and 3P03S1^3P_0- ^3S_1 at 679 nm. Measurements are performed with a frequency chain based on a femtosecond laser referenced to primary frequency standards. They allowed the indirect determination with a 70 kHz uncertainty of the frequency of the doubly forbidden 5s^2^1S_0- 5s5p^3P_0 transition of 87^{87}Sr at 698 nm and in a second step its direct observation. Frequency measurements are performed for 88^{88}Sr and 87^{87}Sr, allowing the determination of 3P0^3P_0, 3P1^3P_1 and 3S1^3S_1 isotope shifts, as well as the 3S1^3S_1 hyperfine constants.Comment: 12 pages, 16 figure

    Atmospheric mercury and fine particulate matter in coastal New England : implications for mercury and trace element sources in the northeastern United States

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    This paper is not subject to U.S. copyright. The definitive version was published in Atmospheric Environment 79 (2013): 760–768, doi:10.1016/j.atmosenv.2013.07.031.Intensive sampling of ambient atmospheric fine particulate matter was conducted at Woods Hole, Massachusetts over a four-month period from 3 April to 29 July, 2008, in conjunction with year-long deployment of the USGS Mobile Mercury Lab. Results were obtained for trace elements in fine particulate matter concurrently with determination of ambient atmospheric mercury speciation and concentrations of ancillary gasses (SO2, NOx, and O3). For particulate matter, trace element enrichment factors greater than 10 relative to crustal background values were found for As, Bi, Cd, Cu, Hg, Pb, Sb, V, and Zn, indicating contribution of these elements by anthropogenic sources. For other elements, enrichments are consistent with natural marine (Na, Ca, Mg, Sr) or crustal (Ba, Ce, Co, Cs, Fe, Ga, La, Rb, Sc, Th, Ti, U, Y) sources, respectively. Positive matrix factorization was used together with concentration weighted air-mass back trajectories to better define element sources and their locations. Our analysis, based on events exhibiting the 10% highest PM2.5 contributions for each source category, identifies coal-fired power stations concentrated in the U.S. Ohio Valley, metal smelting in eastern Canada, and marine and crustal sources showing surprisingly similar back trajectories, at times each sampling Atlantic coastal airsheds. This pattern is consistent with contribution of Saharan dust by a summer maximum at the latitude of Florida and northward transport up the Atlantic Coast by clockwise circulation of the summer Bermuda High. Results for mercury speciation show diurnal production of RGM by photochemical oxidation of Hg° in a marine environment, and periodic traverse of the study area by correlated RGM-SO2(NOx) plumes, indicative of coal combustion sources.We acknowledge support of the USGS Toxic Substances Hydrology Program, the USGS Energy Resources Program, the National Science Foundation Small Grants for Exploratory Research Program, and for initial support, the USGS Mendenhall Postdoctoral Program

    Polarization reversal in KTP single crystals with surface dielectric layer and at elevated temperatures

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    The research was made possible in part by Government of the Russian Federation (Act 211, Agreement 02.A03.21.0006) by RFBR (grant 16-02-00724), and by President of Russian Federation grant for young scientists (Contract 14.Y30.17.2837-MK). The equipment of the Ural Center for Shared Use “Modern nanotechnology” Ural Federal University was used

    Gas emissions, minerals, and tars associated with three coal fires, Powder River Basin, USA.

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    Ground-based surveys of three coal fires and airborne surveys of two of the fires were conducted near Sheridan, Wyoming. The fires occur in natural outcrops and in abandoned mines, all containing Paleocene-age subbituminous coals. Diffuse (carbon dioxide (CO(2)) only) and vent (CO(2), carbon monoxide (CO), methane, hydrogen sulfide (H(2)S), and elemental mercury) emission estimates were made for each of the fires. Additionally, gas samples were collected for volatile organic compound (VOC) analysis and showed a large range in variation between vents. The fires produce locally dangerous levels of CO, CO(2), H(2)S, and benzene, among other gases. At one fire in an abandoned coal mine, trends in gas and tar composition followed a change in topography. Total CO(2) fluxes for the fires from airborne, ground-based, and rate of fire advancement estimates ranged from 0.9 to 780mg/s/m(2) and are comparable to other coal fires worldwide. Samples of tar and coal-fire minerals collected from the mouth of vents provided insight into the behavior and formation of the coal fires

    Dynamic Proteomic Analysis of Pancreatic Mesenchyme Reveals Novel Factors That Enhance Human Embryonic Stem Cell to Pancreatic Cell Differentiation

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    Current approaches in human embryonic stem cell (hESC) to pancreatic beta cell differentiation have largely been based on knowledge gained from developmental studies of the epithelial pancreas, while the potential roles of other supporting tissue compartments have not been fully explored. One such tissue is the pancreatic mesenchyme that supports epithelial organogenesis throughout embryogenesis. We hypothesized that detailed characterization of the pancreatic mesenchyme might result in the identification of novel factors not used in current differentiation protocols. Supplementing existing hESC differentiation conditions with such factors might create a more comprehensive simulation of normal development in cell culture. To validate our hypothesis, we took advantage of a novel transgenic mouse model to isolate the pancreatic mesenchyme at distinct embryonic and postnatal stages for subsequent proteomic analysis. Refined sample preparation and analysis conditions across four embryonic and prenatal time points resulted in the identification of 21,498 peptides with high-confidence mapping to 1,502 proteins. Expression analysis of pancreata confirmed the presence of three potentially important factors in cell differentiation: Galectin-1 (LGALS1), Neuroplastin (NPTN), and the Laminin α-2 subunit (LAMA2). Two of the three factors (LGALS1 and LAMA2) increased expression of pancreatic progenitor transcript levels in a published hESC to beta cell differentiation protocol. In addition, LAMA2 partially blocks cell culture induced beta cell dedifferentiation. Summarily, we provide evidence that proteomic analysis of supporting tissues such as the pancreatic mesenchyme allows for the identification of potentially important factors guiding hESC to pancreas differentiation

    Structural, magnetic and dynamic characterization of liquid crystalline iron(III) Schiff base complexes with asymmetric ligands

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    The iron(III) complexes that were formed by coordination of the Fe III ion with the asymmetric tridentate liquid crystalline Schiff base ligand (L), the water molecules and the different counterions [PF 6 - (1), NO3 - (2), and Cl- (3)] were studied by electron paramagnetic resonance (EPR) spectroscopy. EPR spectroscopy demonstrated that each of the complexes investigated consists of two types of iron centers: S = 1/2 low-spin (LS) and S = 5/2 high-spin (HS). LS iron complexes 2, 3 and LS complex 1 in the temperature range 4.2-250 K have a (dxz,dyz)4(dxy)1 ground state. Interesting features werefound for the monocationic FeIII complex 1, [Fe(L)X(H2O)2]+X-, with X = PF6 - as the counterion. The LS and HS iron centers of 1 are coupled together antiferromagnetically and form a dimer structure by means of the water molecules and the PF6 - counterion. The second-type of LS and HS centers that are visible by means of EPR spectroscopy were best observed in the liquid crystalline (387-405 K) phase. The monitoring and the simulation of the EPR spectra enabled us to trace the dynamics of changing the number of the second-type of LS centers with respect to the first-type of LS centers. The observed dynamic process is characterized by the enthalpy value ΔH = 27.9 kJ/mol, which was caused by reorientation of the PF6 - counterion. Calculation of the observed g values for the second-type of LS complex 1 indicated that, in this case, the (d xy)2(dxz,dyz)3 ground state is stabilized. The conversion between the electron (dxz,d yz)4(dxy)1/(dxy) 2(dxz,dyz)3 configurations was found to be temperature dependent and was detected in the same material for the first time in iron complexes. We synthesized a novel compound, namely a liquid crystalline iron(III) Schiff base complex with the asymmetric ligand [Fe(L)X(H2O)2]+X-, where X = PF 6 - is the counterion. This compound has a labilelow-spin electron configuration that switches between the (dxz,d yz)4(dxy)1/(dxy) 2(dxz,dyz)3 ground states and is temperature-dependent. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

    CariesCare practice guide : consensus on evidence into practice

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    This CariesCare practice guide is derived from the International Caries Classification and Management System (ICCMS) and provides a structured update for dentists to help them deliver optimal caries care and outcomes for their patients. This '4D cycle' is a practice-building format, which both prevents and controls caries and can engage patients as long-term health partners with their practice. CariesCare International (CCI™) promotes a patient-centred, risk-based approach to caries management designed for dental practice. This comprises a health outcomes-focused system that aims to maintain oral health and preserve tooth structure in the long-term. It guides the dental team through a four-step process (4D system), leading to personalised interventions: 1st D: Determine Caries Risk; 2nd D: Detect lesions, stage their severity and assess their activity status; 3rd D: Decide on the most appropriate care plan for the specific patient at that time; and then, finally, 4th D: Do the preventive and tooth-preserving care which is needed (including risk-appropriate preventive care; control of initial non-cavitated lesions; and conservative restorative treatment of deep dentinal and cavitated caries lesions). CariesCare International has designed this practice-friendly consensus guide to summarise best practice as informed by the best available evidence. Following the guide should also increase patient satisfaction, involvement, wellbeing and value, by being less invasive and more health-focused. For the dentist it should also provide benefits at the professional and practice levels including improved medico-legal protection

    Cycling of oxyanion-forming trace elements in groundwaters from a freshwater deltaic marsh

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    Pore waters and surface waters were collected from a freshwater system in southeastern Louisiana to investigate the geochemical cycling of oxyanion-forming trace elements (i.e., Mo, W, As, V). A small bayou (Bayou Fortier) receives input from a connecting lake (Lac des Allemands) and groundwater input at the head approximately 5 km directly south of the Mississippi River. Marsh groundwaters exchange with bayou surface water but are otherwise relatively isolated from outside hydrologic forcings, such as tides, storms, and effects from local navigation canals. Rather, redox processes in the marsh groundwaters appear to drive changes in trace element concentrations. Elevated dissolved S(-II) concentrations in marsh groundwaters suggest greater reducing conditions in the late fall and winter as compared to the spring and late summer. The data suggest that reducing conditions in marsh groundwaters initiate the dissolution of Fe(III)/Mn(IV) oxide/hydroxide minerals, which releases adsorbed and/or co-precipitated trace elements into solution. Once in solution, the fate of these elements is determined by complexation with aqueous species and precipitation with iron sulfide minerals. The trace elements remain soluble in the presence of Fe(III)- and SO4 2-- reducing conditions, suggesting that either kinetic limitations or complexation with aqueous ligands obfuscates the correlation between V and Mo sequestration in sediments with reducing or euxinic conditions
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