Macrophage Migration Inhibitory Factor (MIF) and Its Homologue D-Dopachrome Tautomerase (DDT) Inversely Correlate with Inflammation in Discoid Lupus Erythematosus

Discoid Lupus Erythematosus (DLE) is a chronic cutaneous disease of unknown etiology and of immunoinflammatory origin that is characterized by inflammatory plaques and may lead to disfiguring scarring and skin atrophy. Current treatments are limited, with a large proportion of patients either poorly or not responsive, which makes DLE an unmet medical need. Macrophage migration inhibitory factor (MIF) is the prototype of a pleiotropic family of cytokine that also includes the recently discovered homologue D-dopachrome tautomerase (DDT) or MIF2. MIF and DDT/MIF-2 exert several biological properties, primarily, but not exclusively of a proinflammatory nature. MIF and DDT have been suggested to play a key role in the pathogenesis of several autoimmune diseases, such as multiple sclerosis and type 1 diabetes, as well as in the development and progression of certain forms of cancers. In the present study, we have performed an immunohistochemistry analysis for the evaluation of MIF in DLE lesions and normal skin. We found high levels of MIF in the basal layer of the epidermis as well as in the cutaneous appendage (eccrine glands and sebocytes) of normal skin. In DLE lesions, we observed a significant negative correlation between the expression of MIF and the severity of inflammation. In addition, we performed an analysis of MIF and DDT expression levels in the skin of DLE patients in a publicly available microarray dataset. Interestingly, while these in silico data only evidenced a trend toward reduced levels of MIF, they demonstrated a significant pattern of expression and correlation of DDT with inflammatory infiltrates in DLE skins. Overall, our data support a protective role for endogenous MIF and possibly DDT in the regulation of homeostasis and inflammation in the skin and open up novel avenues for the treatment of DLE.     

<Emphasis Type="Italic">In vitro</Emphasis> bioactivity of 70 wt.% SiO<Subscript>2</Subscript> — 30 wt.% CaO sol-gel glass,doped with 1, 3 and 5 wt.% NbF<Subscript>5</Subscript>

The 70SiO₂-30CaO (wt.%) sol-gel glasses doped with 1, 3 and 5 NbF₅ (wt.%) were prepared via polystep sol-gel route. The synthesized glasses were characterized by XRD, FTIR and SEM. Changes in 1.5 SBF solutions were measured by ICP-AES. XRD of the glasses stabilized at 700°C for 6 hours proved the presence of niocalite. FTIR was consistent with XRD data. The in vitro bioactivity study of all glasses prepared were carried out by soaking in 1.5 simulated body fluid (1.5 SBF) at 37°C for 6 and 12 days in static conditions. The FTIR reveals the formation of A-type and B-type carbonate containing hydroxyapatite (CO₃HA) layer. Changes in 1.5 SBF solutions, after 6 days of soaking, show that the Ca concentration increased significantly, compared to the initial Ca content in the 1.5 SBF solution before in vitro test. After 12 days of immersion, the Ca concentration decreased, i.e., the formation of HA phase consumed Ca from 1.5 SBF solution. For all soaking times, the concentration of P is much lower than that the used 1.5 SBF. Based on these results we suggest that Ca and P play an active role in the future of the glasses. SEM depicts that the different morphology of hydroxyapatite can be formed as a function of soaking time.     

Lessons from the first international proficiency test for the detection of spores from the honey bee pathogen Paenibacillus larvae

We report on the first proficiency test in the context of honey bee disease testing on a broad international scale. Honey samples were distributed to 12 participating laboratories for isolation and identification of spores of the etiological agent of American foulbrood, Paenibacillus larvae. Of the 11 laboratories responding to this proficiency testing event, only 6 (54%) provided data that were in full agreement with the previously determined status of the honey samples; eight (72%) laboratories fell within the threshold for qualification as defined a priori in this proficiency test (=level of agreement of at least 90%). Some lessons can now be drawn from the organizational point of view and will certainly improve new initiatives to be taken.     

Solid-state NMR study of the post-fluorination of (C2.5F)n fluorine-GIC

The conversion of (C2.5F)n fluorine-graphite intercalation compounds (GIC) into covalent graphite fluoride during a post-treatment in pure F2 gas is studied by solid-state NMR. First, a careful characterization of the starting material is performed; in particular, for the first time for fluorinated carbons, two-dimensional 19F--> 13C cross-polarization wide-line separation (CP-WISE) experiments were carried out. This completes the classical NMR data such as 19F and 13C chemical shifts, quantitative 13C solid echo, and C-F bond length measurements, which were estimated by dipolar recoupling using inverse CP MAS. The data of the raw (C2.5F)n and of the samples post-fluorinated at 350, 450, and 550 degrees C were compared to investigate the C-F bonding as a function of the treatment temperature. The C-F bonding is discussed taking into account a hyperconjugation of the C-F bonds with neighboring unfluorinated carbon atoms.     

Intra- vs. intermolecular hydrogen bonding: dimers of alpha-hydroxyesters with methanol

Intermolecular hydrogen bonding competes with an intramolecular hydrogen bond when methanol binds to an alpha-hydroxyester. Disruption of the intramolecular OH...O=C contact in favour of a cooperative OH...OH...O=C sequence is evidenced by FTIR spectroscopy for the addition of methanol to the esters methyl glycolate, methyl lactate and methyl alpha-hydroxyisobutyrate in seeded supersonic jet expansions. Comparison of the OH stretching modes with quantum-chemical harmonic frequency calculations and 18O labelling of methanol unambiguously prove the insertion of methanol into the intramolecular hydrogen bond. This is in marked contrast to UV/IR hole burning studies of the homologous system methyl lactate: (+/-)-2-naphthyl-1-ethanol, where only addition complexes were found and the intramolecular hydrogen bond was conserved. This switch in hydrogen bond pattern from aliphatic to aromatic heterodimers is thought to reflect not only a kinetic propensity but also a thermodynamic preference for addition complexes when dispersion forces become more important in aromatic systems.     

Screening and determination of pesticides in soil using continuous subcritical water extraction and gas chromatography-mass spectrometry

In the present work the efficiency of water under subcritical conditions for the extraction of pesticides having a broad spectrum of polarities from soils was evaluated. The pesticides under study were carbofuran, hexachlorobenzene, dimethoate, simazine, atrazine, lindane, diazinon, methylparathion, alachlor, aldrin-R, metholachlor, chlorpyrifos, heptachlor epoxide, dieldrin, endrin, 4,4-DDT and metoxichlor. Optimization studies were carried out using a blank soil (Non-Polluted Soil 1, CLN-1, RTC) and a real soil which were previously spiked with the pesticide mixture and aged for 60 days. A laboratory-made aluminum oven with controlled temperature was used to carry out the leaching process with subcritical water, where it is placed a pre-heater and the extraction cell. The following variables were studied, keeping the pressure controlled about 1200 p.s.i.: the extraction temperature, the time of static and dynamic extraction and the flow-rate of water (1 p.s.i. = 6894.76 Pa). The extraction efficiency of the pesticides increases with the temperature trending to the quantitative extraction at temperatures near to 300 degrees C. After the extraction process, the analytes were transferred quantitatively to 5 ml dichloromethane, before the determination by GC-MS. The results indicate that under the optimized conditions mostly of the analytes are extracted quantitatively in 90 min with recoveries quite similar to those obtained by the standard Soxhlet extraction procedure. Alternatively, by using an extraction time of 25 min, the method can be used as screening for all the pesticides, with recoveries depending on their polarity.     

Calix[n]arenes as components for the construction of micellar systems: synthesis and self-assembly properties of 5,11,17-Tris[(dimethylamino)methyl]-25-monoalkoxy-26,27,28-trihydroxycalix[4]arene derivatives

A series of mono-O-alkylated calix [4] arenes derivatives, with alkyl chain lengths of between 1 and 12 carbon atoms are reported. Monoalkylation is best achieved using potassium carbonate as the weak base and the respective alkyl iodide for chain lengths of one to three carbon atoms and using caesium fluoride as the base and the respective alkyl iodide for longer chain lengths. The mono-alkylated derivatives were converted into the tri-para-dimethylaminomethylene derivatives by the para-quinonemethide reaction in good yields. Surface tension measurements showed that at pH 2, 4, 6 and 8 all the tri-dimethylaminomethylene derivatives showed surfactant behaviour, and at pH 2 all show a Critical Micellar Concentration values. No correlation between Critical Micellar Concentration values and chain length is observed. Dynamic Light Scattering measurements showed that the CMC behaviour may be correlated with the observed aggregate sizes. The solid state structure of mono-O-ethoxy-calix[4]arene is described, in this structure a 1-D inclusion polymer is observed.     

Absolute configuration of diterpenoids from Jatropha dioica by vibrational circular dichroism

The absolute configuration of jatropholone A 1 and B 2, including the possibility to observe the vibrational circular dichroism (VCD) capacity to differentiate between two epimeric compounds in the presence of an inherently dissymmetric chromophore, which normally dominates VCD and electronic circular dichroism (ECD) spectra, followed after comparison of their experimental and DFT calculated VCD spectra, allowed us to conclude that although non-local (M/P) chirality generated by atropisomerism dominates over local chirality generated by an (R/S) change, the stereogenic center can confidently be assigned by VCD after DFT calculations. In addition, the absolute configurations of jatrophatrione 3 and citlalitrione 4, a compound proposed as a taxonomic marker for the genus Jatropha, were assigned by contrasting their respective calculated and experimental IR and VCD spectra. The evaluation of Flack and Hooft parameters obtained from the single-crystal X-ray diffraction data of jatropholone B acetate 6, and of 4 independently confirmed the absolute configurations of these molecules.     

Dermal Tattoo Biosensors for Colorimetric Metabolite Detection

Tattooing is a ubiquitous body modification involving the injection of ink and/or dye pigments into the dermis. Biosensors in the form of tattoos can be used to monitor metabolites in interstitial fluid. Here, minimally invasive, injectable dermal biosensors were developed for measuring pH, glucose, and albumin concentrations. The dermal pH sensor was based on methyl red, bromothymol blue, and phenolphthalein, which responded to a pH range from 5.0 to 9.0. The dermal glucose sensor consisted of glucose oxidase, 3,3′,5,5′‐tetramethylbenzidine, and peroxidase that detected concentrations up to 50.0 mmol L^?1. The dermal albumin sensor consisted of 3′,3′′,5′,5′′‐tetrachlorophenol‐3,4,5,6‐tetrabromosulfophthalein to measure concentrations up to 5.0 g L^?1. The sensors were multiplexed in ex vivo skin tissue and quantitative readouts were obtained using a smartphone camera. These sensors can be used to manage of acid–base homeostasis, diabetes, and liver failure in point‐of‐care settings.     

Analysis of world terror networks from the reduced Google matrix of Wikipedia

We apply the reduced Google matrix method to analyze interactions between 95 terrorist groups and determine their relationships and influence on 64 world countries. This is done on the basis of the Google matrix of the English Wikipedia (2017) composed of 5 416 537 articles which accumulate a great part of global human knowledge. The reduced Google matrix takes into account the direct and hidden links between a selection of 159 nodes (articles) appearing due to all paths of a random surfer moving over the whole network. As a result we obtain the network structure of terrorist groups and their relations with selected countries including hidden indirect links. Using the sensitivity of PageRank to a weight variation of specific links we determine the geopolitical sensitivity and influence of specific terrorist groups on world countries. The world maps of the sensitivity of various countries to influence of specific terrorist groups are obtained. We argue that this approach can find useful application for more extensive and detailed data bases analysis.