Alcohol consumption and liver phenotype of individuals with alpha‐1 antitrypsin deficiency

Background and Aims: Alpha‐1 antitrypsin deficiency is an inherited disorder caused by alpha‐1 antitrypsin (AAT) mutations. We analysed the association between alcohol intake and liver‐related parameters in individuals with the heterozygous/homozygous Pi*Z AAT variant (Pi*MZ/Pi*ZZ genotype) found in the United Kingdom Biobank and the European Alpha1 liver consortium. Methods: Reported alcohol consumption was evaluated in two cohorts: (i) the community‐based United Kingdom Biobank (17 145 Pi*MZ, 141 Pi*ZZ subjects, and 425 002 non‐carriers [Pi*MM]); and (ii) the European Alpha1 liver consortium (561 Pi*ZZ individuals). Cohort (ii) included measurements of carbohydrate‐deficient transferrin (CDT). Results: In both cohorts, no/low alcohol intake was reported by &gt;80% of individuals, while harmful consumption was rare (~1%). Among Pi*MM and Pi*MZ individuals from cohort (i), moderate alcohol consumption resulted in a &lt;30% increased rate of elevated transaminases and ~50% increase in elevated gamma-glutamyl transferase values, while harmful alcohol intake led to an at least twofold increase in the abnormal levels. In Pi*ZZ individuals from both cohorts, moderate alcohol consumption had no marked impact on serum transaminase levels. Among Pi*ZZ subjects from cohort (ii) who reported no/low alcohol consumption, those with increased CDT levels more often had signs of advanced liver disease.Conclusions: Pi*MZ/Pi*ZZ genotype does not seem to markedly aggravate the hepatic toxicity of moderate alcohol consumption. CDT values might be helpful to detect alcohol consumption in those with advanced fibrosis. More data are needed to evaluate the impact of harmful alcohol consumption.<br/

Differential Lyn-dependence of the SHIP1- deficient mast cell phenotype

Lyn/Ca2+/calcineurin-dependent signaling controls Ag-induced transcription of differential genes. Wt, Lyn-/-, SHIP1-/-, and dko BMMCs were left unstimulated (con) or stimulated with Ag (20 ng/ml) for 90 min. The amounts of Tnfsf9 mRNA (A), Tnip3 mRNA (B), Il1a mRNA (C), Il1b mRNA (D), and Stx11 mRNA (E) were measured by RT-qPCR. A comparison of analyses of different independent cell cultures is depicted. The results shown in Fig. 5a are indicated. (PDF 534 kb

Size- and Surface-Dependent Solubility of Cadmium Telluride in Aqueous Solutions

Due to the toxicity of cadmium (Cd) and the scarcity of telluride (Te), CdTe-based photovoltaic modules have been under discussion during the last few years. In particular, the stability of CdTe in aqueous solutions is under debate. Here we show that the stability of CdTe depends not only on the pH of water-based solutions but also on size and surface treatment of CdTe particles. We compare milled module pieces with CdTe powders of different particle size. The leaching of CdTe is conditioned by the outdiffusion of Cd and Te at the interface between CdTe particles and the aqueous solution. The smaller the particle size, the faster the leaching. Therefore, milled module pieces decompose faster than CdTe powders with relatively large grains. We observe a dependence on time t according to t0.43. The room temperature diffusion coefficients are calculated as DCd ≈ 3 × 10−17 cm2/s for Cd, and DTe ≈ 1.5 × 10−17 cm2/s for Te in pH4. The chemical instability in aqueous solutions follows thermodynamic considerations. The solution behavior of Cd and Te depends on the pH value and the redox potential of the aqueous solutions. Chemical treatments such as those used in solar cell production modify the surface of the CdTe particles and their leaching behavior

Secretory lysosomes of mouse mast cells store and exocytose active caspase-3 in a strictly granzyme B dependent manner

In this study, we report that cytoplasmic granules from in vivo and in vitro derived mouse mast cells (MCs) contain active granzyme B (gzmB) and caspase-3, which is consistent with recent findings. Studying WT and gzmB-deficient mice, we observed that BM-derived MCs (BMMCs) from both strains contain cytosolic pro-caspase-3, but only WT BMMCs expressed active caspase-3 limited to their secretory lysosomes. Confocal microscopy revealed colocalization of active caspase-3 and gzmB in these cytoplasmic granules. The combined data demonstrate that the generation and storage of active caspase-3 is gzmB-dependent. The finding that BMMCs secrete caspase-3 and gzmB after Ag stimulation suggests that both proteases contribute to extracellular MC-mediated proteolytic events. Although the extracellular function of MC-derived caspase-3 remains unclear, we show that BMMC-secreted caspase-3 cleaves IL-33, a cytokine that contributes to the development of asthma and arthritis. We also show that an in vitro propagated cytolytic T-lymphocyte line constitutively expresses gzmB together with active caspase-3, suggesting a novel interaction of these proteases in the execution of multiple innate and adaptive immune responses

Size- and Surface-Dependent Solubility of Cadmium Telluride in Aqueous Solutions

Due to the toxicity of cadmium (Cd) and the scarcity of telluride (Te), CdTe-based photovoltaic modules have been under discussion during the last few years. In particular, the stability of CdTe in aqueous solutions is under debate. Here we show that the stability of CdTe depends not only on the pH of water-based solutions but also on size and surface treatment of CdTe particles. We compare milled module pieces with CdTe powders of different particle size. The leaching of CdTe is conditioned by the outdiffusion of Cd and Te at the interface between CdTe particles and the aqueous solution. The smaller the particle size, the faster the leaching. Therefore, milled module pieces decompose faster than CdTe powders with relatively large grains. We observe a dependence on time t according to t0.43. The room temperature diffusion coefficients are calculated as DCd &asymp; 3 &times; 10&minus;17 cm2/s for Cd, and DTe &asymp; 1.5 &times; 10&minus;17 cm2/s for Te in pH4. The chemical instability in aqueous solutions follows thermodynamic considerations. The solution behavior of Cd and Te depends on the pH value and the redox potential of the aqueous solutions. Chemical treatments such as those used in solar cell production modify the surface of the CdTe particles and their leaching behavior

Additional file 1: Figure S1. of Differential Lyn-dependence of the SHIP1-deficient mast cell phenotype

Impaired Ca2+ mobilization in Lyn-/- BMMCs is independent of the stimulus concentration. Wt and Lyn-/- BMMCs were preloaded and starved overnight with 0.15 μg/ml IgE. Ca2+ mobilization was measured for 4 min by flow cytometry using the Ca2+-sensitive fluorescent dyes fluo-3 (Ca2+ b) and fura red (Ca2+ ub). Steady-state fluorescence was assessed for 1 min before BMMCs were stimulated with the indicated Ag concentrations. The arrow marks the time point of stimulus addition. Comparable results were obtained with cells from different BMMC cultures (n = 3). (PDF 289 kb