Epigenetic dynamics of monocyte-to-macrophage differentiation

Background Monocyte-to-macrophage differentiation involves major biochemical and structural changes. In order to elucidate the role of gene regulatory changes during this process, we used high-throughput sequencing to analyze the complete transcriptome and epigenome of human monocytes that were differentiated in vitro by addition of colony-stimulating factor 1 in serum-free medium. Results Numerous mRNAs and miRNAs were significantly up- or down-regulated. More than 100 discrete DNA regions, most often far away from transcription start sites, were rapidly demethylated by the ten eleven translocation enzymes, became nucleosome-free and gained histone marks indicative of active enhancers. These regions were unique for macrophages and associated with genes involved in the regulation of the actin cytoskeleton, phagocytosis and innate immune response. Conclusions In summary, we have discovered a phagocytic gene network that is repressed by DNA methylation in monocytes and rapidly de-repressed after the onset of macrophage differentiation

Effects of opioids on human serotonin transporters.

The serotonin (5-hydroxtryptamine, 5-HT) system plays a role in analgesia and emesis. The aim of this study was to test whether opioids or ketamine inhibit the human 5-HT transporter and whether this increases free plasma 5-HT concentrations. HEK293 cells, stably transfected with the human 5-HT transporter cDNA, were incubated with morphine, hydromorphone, fentanyl, alfentanil, pethidine (meperidine), tramadol, ketamine, and the reference substance citalopram (specific 5-HT transporter inhibitor). The uptake of [(3)H]5-HT was measured by liquid scintillation counting. In a second series of experiments, study drugs were incubated with plasma of ten healthy blood donors and change of 5-HT plasma-concentrations were measured (ELISA). The end point was the inhibition of the 5-HT transporter by different analgesics either in HEK293 cells or in human platelets ex vivo. Tramadol, pethidine, and ketamine suppressed [(3)H]5-HT uptake dose-dependently with an IC50 of 1, 20.9, and 230 μM, respectively. These drugs also prevented 5-HT uptake in platelets with an increase in free plasma 5-HT. Free 5-HT concentrations in human plasma were increased by citalopram 1 μM, tramadol 20 μM, pethidine 30 μM, and ketamine 100 μM to 280 [248/312]%, 269 [188/349]%, and 149 [122/174]%, respectively, compared to controls without any co-incubation (means [95 % CI]; all p < 0.005). No change in both experimental settings was observed for the other opioids. Tramadol and pethidine inhibited the 5-HT transporter in HEK293 cells and platelets. This inhibition may contribute to serotonergic effects when these opioids are given in combination, e.g., with monoamine oxidase inhibitors or selective serotonin reuptake inhibitors

Pseudomonas Strains Naturally Associated with Potato Plants Produce Volatiles with High Potential for Inhibition of Phytophthora infestans

Bacteria emit volatile organic compounds with a wide range of effects on bacteria, fungi, plants, and animals. The antifungal potential of bacterial volatiles has been investigated with a broad span of phytopathogenic organisms, yet the reaction of oomycetes to these volatile signals is largely unknown. For instance, the response of the late blight-causing agent and most devastating oomycete pathogen worldwide, Phytophthora infestans, to bacterial volatiles has not been assessed so far. In this work, we analyzed this response and compared it to that of selected fungal and bacterial potato pathogens, using newly isolated, potato-associated bacterial strains as volatile emitters. P. infestans was highly susceptible to bacterial volatiles, while fungal and bacterial pathogens were less sensitive. Cyanogenic Pseudomonas strains were the most active, leading to complete growth inhibition, yet noncyanogenic ones also produced antioomycete volatiles. Headspace analysis of the emitted volatiles revealed 1-undecene as a compound produced by strains inducing volatile-mediated P. infestans growth inhibition. Supplying pure 1-undecene to P. infestans significantly reduced mycelial growth, sporangium formation, germination, and zoospore release in a dose-dependent manner. This work demonstrates the high sensitivity of P. infestans to bacterial volatiles and opens new perspectives for sustainable control of this devastating pathogen

Thermal oxidation behavior of glass-forming Ti–Zr–(Nb)–Si alloys

The glass-forming Ti₇₅Zr₁₀Si₁₅ and Ti₆₀Zr₁₀Nb₁₅Si₁₅ alloys composed of nontoxic elements may represent new materials for biomedical applications. For this study, melt-spun alloy samples exhibiting glass–matrix nanocomposite structures were subjected to thermal oxidation treatments in synthetic air to improve their surface characteristics. 550 °C was identified as the most appropriate temperature to carry out oxidative surface modifications while preserving the initial metastable microstructure. The modified surfaces were evaluated considering morphological and structural aspects, and it was found that the oxide films formed at 550 °C are amorphous and consist mainly of TiO₂; their thicknesses were estimated to be ~560 nm for Ti₇₅Zr₁₀Si₁₅ and ~460 nm for Ti₆₀Zr₁₀Nb₁₅Si₁₅. The thermally treated sample surfaces exhibit not only higher roughnesses and higher hardnesses but also improved wettability compared to the as-spun materials. By immersion of oxidized samples in simulated body fluid Ca- and P-containing coatings exhibiting typical morphologies of apatite are formed

NMP and TXIB induce oxidative stress <i>in vitro</i> and <i>in vivo.</i>

<p>A549 human lung epithelial cells were exposed to NMP or TXIB for 24 h. Expression of GSTP-1 was quantified by western blotting (A). Naïve mice were exposed to NMP or TXIB on two consecutive days for 6 hours, lung tissues were taken and GSTP-1 expression was quantified by western blotting (B) and 8-isoprostane (C) was measured as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0039817#pone.0039817.s003" target="_blank">File S1</a>. In the pseudoimages, the blue to red coloring represents the lowest to the highest light intensity in NMP (52 µg/m³)- or TXIB (31 µg/m³)-exposed NFκB/luciferase transgenic mice (D). Photon emission was quantified over the lung area (arrow) as mean fold of induction (E). Data are expressed as mean ± SEM from three independent experiments (A), n ≥ 9 animals per group (B, C) or <i>n</i> = 4 per group (D, E); *<i>p</i><0.05 <i>vs</i>. CON.</p

Increased acute allergic immune response by PVC flooring is abrogated by the antioxidant NAC.

<p>Treatment of Balb/c mice with NAC (1g/l) during exposure to PVC flooring reduced the enhanced acute airway inflammation (A), the number of eosinophils in the BAL fluid (B), OVA-specific IgE levels (C), IL-13 and IL-5 cytokine levels (D) and the production of 8-isoprostane in lung homogenates (E) compared to NAC-untreated mice. Data are expressed as mean ± SEM, n ≥ 9 animals per group; *<i>P</i><0.05, PVC flooring <i>vs.</i> OVA; ^#P<0.05, PVC flooring <i>vs</i>. PVC flooring + NAC.</p