IgG from Adult Atopic Dermatitis (AD) Patients Induces Thymic IL-22 Production and CLA Expression on CD4+ T Cells: Possible Epigenetic Implications Mediated by miRNA

Atopic dermatitis (AD) is a common relapsing inflammatory skin disorder characterized by immune-mediated inflammation and epidermal barrier dysfunction. The pathogenesis of AD is multifactorial and has not been fully elucidated to date. This study aimed to evaluate whether serum IgG from adult AD patients could modulate the thymic maturation of IL-22-producing T cells and CLA+ T cells of non-atopic infants. Given that miRNAs regulate immune response genes, we evaluated whether miRNA expression is also altered in cultured thymocytes. Thymocytes were cultured with purified IgG from AD patients or control conditions (mock, Intravenous-IgG (IVIg), non-atopic IgG, or atopic non-AD IgG). Using flow cytometry analysis, we assessed the expression of CLA and intracellular levels of IL-4, IFN-γ, and IL-22 on double-positive T cells (DP T), CD4 T cells, or CD8 T cells. We also investigated the frequency of IgG isotypes and their direct interaction with the thymic T cells membrane. The miRNA profiles were evaluated by the Illumina small RNA-seq approach. MiRNA target gene prediction and enrichment analyses were performed using bioinformatics. Increased frequencies of IL-22 and CLA+ producing CD4+ T cells cultured with IgG of AD patients was seen in non-atopic infant thymocytes compared to all control conditions. No alterations were observed in the frequency of IgG isotypes among evaluated IgG pools. Evidence for a direct interaction between IgG and thymic DP T, CD4 T, and CD8 T cells is presented. The small RNA-seq analysis identified ten mature miRNAs that were modulated by AD IgG compared to mock condition (miR-181b-5p, hsa-miR-130b-3p, hsa-miR-26a-5p, hsa-miR-4497, has-miR-146a, hsa-let-7i-5p, hsa-miR-342-3p, has-miR-148a-3p, has-miR-92a and has-miR-4492). The prediction of the targetome of the seven dysregulated miRNAs between AD and mock control revealed 122 putative targets, and functional and pathway enrichment analyses were performed. Our results enhance our understanding of the mechanism by which IgG can collaborate in thymic T cells in the setting of infant AD.     

Novel fluorine containing polyfluorenes with efficient blue electroluminescence

The synthesis, structural characterization, photo and electroluminescence, thermal and electrochemical properties of a new fluorinated fluorene-containing copolymer are described. The copolymer is formed by alternating mers of [2,3,5,6 tetrafluoro-1,4 phenylene] and [9,9′-dihexyl-2,7 fluorene] and emits blue light with low turn on voltages. The EL performance of the fluorinated copolymer was superior to those of the non-fluorinated analog copolymer and of the corresponding poly(9,9′dihexyl-2,7 polyfluorene) homopolymer.     

Unmasking Sensory Defects of Olive Oils Flavored with Basil and Oregano Using an Electronic Tongue-Chemometric Tool

Olive oil price and consumers’ preference depend on the commercial grade classification that can decrease if any sensory defect is perceived leading to an economic loss. Enriched oils, obtained by incorporating dried aromatic herbs, spices, or essential oils, which is a common practice in the Mediterranean region, are commercially available. This practice may conceal the fraudulent purpose of masking the perception of sensory defects. The detection of this type of fraud is a difficult task, requiring sensory analysis. Thus, in this study, extra-virgin and lampante olive oils, the latter classification being due to the perception of an intense winey-vinegary defect, were deliberately enriched with different amounts of basil-dried herbs and oregano-dried herbs. Sensory analysis showed that, depending on the aromatic herb and on the added amount (0.011–0.110 g herb per kg oil), the defect intensity could be masked leading to an erroneous classification of flavored lampante oils as flavored virgin oils. In contrast, the electronic tongue-chemometric approach could unmask the defect in flavored oils (predictive sensitivities: 70–78%) and semiquantitatively discriminate flavored oils according to the added levels of basil or oregano (predictive sensitivities: 93–100%). The electronic tongue approach showed satisfactory unmasking performance when compared with the sensory panel, and so, its future application as a quality control taste-sensor device for disclosing olive oil sensory defects masked by the incorporation of flavoring agents may be forseen.     

Combining 1,3-Ditriazolylbenzene and Quinoline to Discover a New G-Quadruplex-Interactive Small Molecule Active against Cancer Stem-Like Cells

Quadruplex nucleic acids are promising targets for cancer therapy. In this study we used a fragment-based approach to create new flexible G-quadruplex (G4) DNA-interactive small molecules with good calculated oral drug-like properties, based on quinoline and triazole heterocycles. G4 melting temperature and polymerase chain reaction (PCR)-stop assays showed that two of these compounds are selective G4 ligands, as they were able to induce and stabilize G4s in a dose- and DNA sequence-dependent manner. Molecular docking studies have suggested plausible quadruplex binding to both the G-quartet and groove, with the quinoline module playing the major role. Compounds were screened for cytotoxicity against four cancer cell lines, where 4,4′-(4,4′-(1,3-phenylene)bis(1H-1,2,3-triazole-4,1-diyl))bis(1-methylquinolin-1-ium) ( 1 d ) showed the greater activity. Importantly, dose–response curves show that 1 d is cytotoxic in the human colon cancer HT-29 cell line enriched in cancer stem-like cells, a subpopulation of cells implicated in chemoresistance. Overall, this study identified a new small molecule as a promising lead for the development of drugs targeting G4 in cancer stem cells.     

Study of the vertical transport in <Emphasis Type="Italic">p</Emphasis>-doped superlattices based on group III-V semiconductors

The electrical conductivity σ has been calculated for p-doped GaAs/Al_0.3Ga_0.7As and cubic GaN/Al_0.3Ga_0.7N thin superlattices (SLs). The calculations are done within a self-consistent approach to the theory by means of a full six-band Luttinger-Kohn Hamiltonian, together with the Poisson equation in a plane wave representation, including exchange correlation effects within the local density approximation. It was also assumed that transport in the SL occurs through extended minibands states for each carrier, and the conductivity is calculated at zero temperature and in low-field ohmic limits by the quasi-chemical Boltzmann kinetic equation. It was shown that the particular minibands structure of the p-doped SLs leads to a plateau-like behavior in the conductivity as a function of the donor concentration and/or the Fermi level energy. In addition, it is shown that the Coulomb and exchange-correlation effects play an important role in these systems, since they determine the bending potential.     

SEM study of the morphology of asymmetric cellulose acetate membranes produced from recycled agro-industrial residues: sugarcane bagasse and mango seeds

Cellulose, obtained both from sugarcane bagasse and mango seeds, was used for synthesizing cellulose acetate in order to produce asymmetric membranes. These were compared to membranes of commercial cellulose acetate (Rhodia). All produced membranes were asymmetric, characterized by the presence of a dense skin and a porous support. Differences regarding the morphology of the surfaces as well as of the porous support can be noticed. Scanning Electron Microscopy (SEM) showed that the morphology of the superficial layer, responsible for transport, depends on the different lignin content of the starting material and also on the viscosity average molecular weight of the cellulose acetates produced from sugarcane bagasse, mango seed, and Rhodia’s commercial cellulose acetate.     

Nitrogen-use efficiency and economic efficiency of slow-release N fertilisers applied to irrigated turfs in a Mediterranean environment

The effect of three fertilisers that delay the bioavailability of nitrogen (N) in the soil was compared with ammonium nitrate and a zero N control in two irrigated turfs in NE Portugal. The fertilisers used were: Floranid permanent 16-7-15 (slow-release, IBDU/Isodur fertiliser); Basacote plus 9M 16-8-12 (controlled-release fertiliser, copolymer ethylene acrylic); Nitroteck 20-8-10 (stabilized fertiliser, dicyandiamide as nitrification inhibitor + coating with polyterpene) and Nitrolusal (ammonium nitrate, 20.5% N), applied all at a rate of 120 kg N ha⁻¹. Nitrolusal was split into two fractions of 60 kg N ha⁻¹. Phosphorus (P) and potassium (K) rates were balanced among treatments by using superphosphate (18% P₂O₅) and potassium chloride (60% K₂O). The turf dry matter (DM) yield and N concentration in dry material were determined from several cuts of biomass throughout the growing season. Based on DM yield, N concentration in dry material and fertilisation costs, indices of N use efficiency and economic efficiency were estimated. Soil nitrate levels were monitored by using anion exchange membranes inserted directly into the soil. Basacote gave significantly lower DM yields than the other fertilised treatments. The apparent N recovery of Basacote was also the lowest. The results showed that Basacote released less N than that required for an adequate plant growth in the beginning of the growing season, hampered the flush of spring growth. Furthermore, the release period of this Basacote formulation, in the environmental conditions of these experiments, seemed to be longer than the length of the growing season. Nitroteck and Floranid yielded similar or even higher DM and apparent N recovery values than did Nitrolusal. The indices of economic efficiency ordered the fertilisers as Nitroteck > Nitrolusal > Floranid > Basacote or Nitrolusal > Nitroteck > Floranid > Basacote, if the costs of P and K fertilisers used to balance the P and K rates in the experimental design were, respectively, taken or not taken into account.     

Real‐time monitoring by proton relaxometry of radical polymerization reactions of acrylamide in aqueous solution

The potential of time‐domain nuclear magnetic resonance (TD‐NMR) for the real‐time monitoring of solution radical polymerizations is demonstrated. A model system composed of a redox‐pair initiator system, acrylamide as monomer and water as solvent was investigated. A second‐generation continuous wave free precession technique was employed to measure the longitudinal relaxation time constant (T₁) of the samples throughout the polymerization reactions. This parameter was shown to be sensitive to the reactant feed free‐radical enhancement of the water molecule relaxation time, making it a good probe to monitor monomer conversion in real time in an automated, non‐destructive fashion. It was found that the T₁ value was better than the transverse relaxation time constant (T₂) for describing the evolution of the polymerization reactions, due to its greater sensitivity to paramagnetic effects. The TD‐NMR signal variation observed was linked to the formation, propagation and termination steps of the radical polymerization kinetics scheme. These first results may contribute to the application of real‐time monitoring of radical polymerization reactions employing low‐cost and robust TD‐NMR spectrometers. © 2018 Society of Chemical Industry     

Ionic conductivities and high resolution microscopic evaluation of grain and grain boundaries of cerium-based codoped solid electrolytes

Doped CeGdO and codoped CeGdOSmO compositions were synthesized, giving rise to nanoparticulate powders. Ionic conductivities at bulk and grain boundaries of the sintered samples were determined, exhibiting increased conductivity in the samaria-codoped samples. Scanning electron microscopy (SEM) showed a significant reduction in the grain size of samaria-codoped electrolytes. This reduced grain size of the codoped samples caused a reduction in Schottky barrier height, increasing oxygen vacancy concentration in the space-charge layer of the grain boundary and culminating in greater ionic conductivity in the boundary region. For the gadolinium doped samples, high resolution transmission electron microscopy images at grains showed the presence of large cluster of defects (nanodomains), hindering the movement of charge carriers and reducing ionic conductivity. However, the samaria-codoped system displayed better homogeneity at atomic level, resulting in reduced oxygen vacancy ordering and, consequently, smaller nanodomains and higher bulk (grain) conductivity. The reduced grain sizes and smaller nanodomains caused by codoping favor the ionic conductivity of ceria-based ceramics, doped with gadolinia and codoped with samaria.     

Insight into the Mechanism of Phenylacetate Decarboxylase (PhdB), a Toluene-Producing Glycyl Radical Enzyme

We recently reported the discovery of phenylacetate decarboxylase (PhdB), representing one of only ten glycyl-radical-enzyme reaction types known, and a promising biotechnological tool for first-time biochemical synthesis of toluene from renewable resources. Here, we used experimental and computational data to evaluate the plausibility of three candidate PhdB mechanisms, involving either attack at the phenylacetate methylene carbon or carboxyl group [via H-atom abstraction from COOH or single-electron oxidation of COO⁻ (Kolbe-type decarboxylation)]. In vitro experimental data included assays with F-labeled phenylacetate, kinetic studies, and tests with site-directed PhdB mutants; computational data involved estimation of reaction energetics using density functional theory (DFT). The DFT results indicated that all three mechanisms are thermodynamically challenging (beyond the range of many known enzymes in terms of endergonicity or activation energy barrier), reflecting the formidable demands on PhdB for catalysis of this reaction. Evidence that PhdB was able to bind α,α-difluorophenylacetate but was unable to catalyze its decarboxylation supported the enzyme's abstraction of a methylene H atom. Diminished activity of H327A and Y691F mutants was consistent with proposed proton donor roles for His327 and Tyr691. Collectively, these and other data most strongly support PhdB attack at the methylene carbon.