Immune sensing of nucleic acids in inflammatory skin diseases.

Endosomal and cytosolic nucleic acid receptors are important immune sensors required for the detection of infecting or replicating viruses. The intracellular location of these receptors allows viral recognition and, at the same time, avoids unnecessary immune activation to self-nucleic acids that are continuously released by dying host cells. Recent evidence, however, indicates that endogenous factors such as anti-microbial peptides have the ability to break this protective mechanism. Here, we discuss these factors and illustrate how they drive inflammatory responses by promoting immune recognition of self-nucleic acids in skin wounds and inflammatory skin diseases such as psoriasis and lupus.

Muurahaishapon käyttö etikkahapon ja propionihapon sovelluksissa

Työssä tutkittiin muurahais-, etikka- ja propionihapon sekä näiden johdannaisten teollisia sovelluskohteita. Työn tarkoituksena oli löytää muurahaishapolle tai sen johdannaisille potentiaalisia käyttökohteita etikka- ja propionihapon sekä näiden johdannaisten teollisista sovelluskohteista. Työssä on laaja kirjallisuuskatsaus, jossa käsitellään muurahais-, etikka- ja propionihapon kemiallisia ja fysikaalisia ominaisuuksia, ekologisia ja korroosiovaikutuksia sekä yleensä orgaanisten happojen antimikrobisia ominaisuuksia. Tämän lisäksi työssä esitellään tarkasteltavien happojen sekä happojohdannaisten markkinat teollisissa sovelluksissa Yhdysvalloissa, Länsi-Euroopassa ja Japanissa. Korvaavuuksien syventävän analyysin avulla pyrittiin löytämään ne sovelluskohteet muurahaishapolle tai sen johdannaisille, joissa ne voisivat olla hinnaltaan kilpailukykyisiä vastaavien etikka-ja propionihapposovellusten kanssa. Mahdollisen korvaavuuden rajaksi asetettiin5 000 tonnia sovelluskohdetta kohti. Kirjallisuustutkimuksen perusteella etikkahapon estereiden (asetaattiestereiden) käyttökohde liuottimien komponentteinavoisi olla potentiaalisin käyttökohde vastaaville muurahaishapon estereille (formiaattiestereille). Asetaattiestereitä on ennustettu käytettävän maailmalla 2 808 000 tonnia vuonna 2006. Niiden pääkäyttöalueet ovat liuottimina pintapäällysteissä kuten maaleissa, lakoissa sekä painomusteissa ja -väreissä. Toistaiseksi formiaattiestereitä on hyödynnetty vain muutamia satoja tonneja lähinnä lääketeollisuuden sovelluksissa välituotteena. Työssä tehtyjen alustavien laskelmien perusteella muurahaishapon esterit ovat hintatasoltaan kilpailukykyinen vaihtoehto vastaaville asetaattiestereille. Diplomityön kokeellisessa osassa etyyliformiaattia valmistettiin menestyksekkäästi laboratoriomittakaavassa. Toinen potentiaalinen uusi tuote on selluloosaformiaattikuitu (SF-kuitu). Selluloosa-asetaattikuitua käytettiin vuonna 2001 845 000 tonnia, josta 79 % kului savukefilttereiden valmistukseen. SF-kuitu on kirjallisuuden mukaan vaihtoehtoinen raaka-aine savukefilttereiden valmistukseen.

Milk yield and reproductive performance of dairy heifers and cows supplemented with polyunsaturated fatty acids

The objective of this work was to determine productive and fertility responses of Holstein-Friesian heifers and cows to supplementation with extruded linseed and soybean as sources of polyunsaturated fatty acids (PUFAs). Supplementation had a positive effect on profitability, with significant increases in milk yield in supplemented cows, but not in heifers. Treatments had no effect on milk fat content, but higher milk protein contents were observed with supplementation. A higher conception rate was found for supplemented heifers, but not for cows. Fat sources containing PUFAs are recommended for dairy cattle supplementation, since they improve fertility in heifers and milk yield in cows.

Effect of n-3 fatty acids on markers of brain injury and incidence of sepsis-associated delirium in septic patients.

BACKGROUND: Data regarding immunomodulatory effects of parenteral n-3 fatty acids in sepsis are conflicting. In this study, the effect of administration of parenteral n-3 fatty acids on markers of brain injury, incidence of sepsis-associated delirium, and inflammatory mediators in septic patients was investigated. METHODS: Fifty patients with sepsis were randomized to receive either 2 ml/kg/day of a lipid emulsion containing highly refined fish oil (equivalent to n-3 fatty acids 0.12 mg/kg/day) during 7 days after admission to the intensive care unit or standard treatment. Markers of brain injury and inflammatory mediators were measured on days 1, 2, 3 and 7. Assessment for sepsis-associated delirium was performed daily. The primary outcome was the difference in S-100β from baseline to peak level between both the intervention and the control group, compared by t-test. Changes of all markers over time were explored in both groups, fitting a generalized estimating equations model. RESULTS: Mean difference in change of S-100β from baseline to peak level was 0.34 (95% CI: -0.18-0.85) between the intervention and control group, respectively (P = 0.19). We found no difference in plasma levels of S-100β, neuron-specific enolase, interleukin (IL)-6, IL-8, IL-10, and C-reactive protein between groups over time. Incidence of sepsis-associated delirium was 75% in the intervention and 71% in the control groups (risk difference 4%, 95% CI -24-31%, P = 0.796). CONCLUSION: Administration of n-3 fatty acids did not affect markers of brain injury, incidence of sepsis-associated delirium, and inflammatory mediators in septic patients.

Potentiometric titration as a method of determining the stoichiometric dissociation constants of weak acids from the thermodynamic dissociation constants of aqueous solutions at 298.15 K

The simple single-ion activity coefficient equation originating from the Debye-Hückel theory was used to determine the thermodynamic and stoichiometric dissociation constants of weak acids from data concerning galvanic cells. Electromotive force data from galvanic cells without liquid junctions, which was obtained from literature, was studied in conjuction with the potentiometric titration data relating to aqueous solutions at 298.15 K. The dissociation constants of weak acids could be determined by the presented techniques and almost all the experimental data studied could be interpreted within the range of experimental error. Potentiometric titration has been used here and the calculation methods were developed to obtain the thermodynamic and stoichiometric dissociation constants of some weak acids in aqueous solutions at 298.15 K. The ionic strength of titrated solutions were adjusted using an inert electrolyte, namely, sodium or potassium chloride. Salt content alonedetermines the ionic strength. The ionic strength of the solutions studied varied from 0.059 mol kg-1 to 0.37 mol kg-1, and in some cases up to 1.0 mol kg-1. The following substances were investigated using potentiometric titration: aceticacid, propionic acid, L-aspartic acid, L-glutamic acid and bis(2,2-dimethyl-3-oxopropanol) amine.

Reduction of conjugated dienoic carboxylic acids and esters with sodium dithionite

Reduction of 2,4-alkadienoic acids and esters with sodium dithionite was carried out in aqueous solution or under PTC conditions to give, almost exclusively, Z:E isomeric mixtures of the corresponding 3-alkenoic acids and esters, respectively, in good yields.

Effect of feed fat by-products with trans fatty acids and heated oil on cholesterol and oxycholesterols in chicken

Chicken is the most widely consumed meat all over the world due to chickens being easy to rear, their fast growth rate and the meat having good nutritional characteristics. The main objective of this paper was to study the effects of dietary fatty by-products in low, medium and high levels of oxidized lipids and trans fatty acids (TFAs) on the contents of cholesterol and oxycholesterols in meat, liver, and plasma of chickens. A palm fatty acid distillate, before and after hydrogenation, and a sunflower-olive oil blend (70/30, v/v) before and after use in a commercial frying process were used in feeding trials after adding 6% of the fats to the feeds. Highly oxidized lipid and TFA feeds significantly increased the contents of cholesterol and oxycholesterols in all tissues of chicken (0.01 < p <= 0.05). The contents of oxycholesterols in chicken meat, liver and plasma obtained from TFA feeding trials varied between 17 and 48 μg/100 g in meat, 19-42 μg/100 g in liver and 105-126 μg/dL in plasma. In contrast, in the oxidized lipid feeding trials, oxycholesterols varied between 13 and 75 μg/100 g in meat, 30-58 μg/100 g in liver and 66-209 μg/dL in plasma. Meat from chickens fed with feeds containing high levels of TFAs or oxidized lipids may contribute to higher ingestion of cholesterol and oxycholesterols by humans.

GROWTH, YIELD AND POSTHARVEST QUALITY OF WAX APPLE AS AFFECTED BY NAPHTHALENE ACETIC ACID APPLICATION

Results of this study represent the first report of the effect of Naphthalene Acetic Acid (NAA) on the pre and post harvest quality of wax apple fruit. The wax apple trees were spray treated with 0, 5, 10 and 20 mg L-1 NAA under field conditions during 2008 to 2011. The experiments were carried out in Completely Randomized Design (CRD) with six replications. Leaf chlorophyll content, chlorophyll fluorescence, photosynthetic yield, net photosynthetic rate, drymatter content of leaves and total soluble solids and K+content of wax apple fruits were significantly increased after treatments with 10 mg L-1. Polygalacturonase activity significantly decreased with NAA treatments. The application of 5 mg L-1 NAA increased 27% more bud and reduced 42% less fruit drop compared to the control. In addition, higher protein and phosphate synthase activity of leaves, fruit set, fruit growth, larger fruit size and yield were recorded in NAA treated plants. In storage, treated fruits exhibited higher TSS and firmness and less weight loss, browning, titratable acidity, respiration and ethylene production than the control. It is concluded that spraying with 5 and 10 mg L-1 NAA once a week under field conditions produced better fruit growth and yield of the wax apple and maintained better fruit quality in postharvest storage.

Long-term effects of Roux-en-Y gastric bypass on postprandial plasma lipid and bile acids kinetics in female non diabetic subjects: A cross-sectional pilot study.

BACKGROUND AND AIMS: Formerly obese patients having undergone Roux-en-Y gastric bypass (RYGB) display both an accelerated digestion and absorption of carbohydrate and an increased plasma glucose clearance rate after meal ingestion. How RYGB effects postprandial kinetics of dietary lipids has yet not been investigated. METHODS: Plasma triglyceride (TG), apoB48, total apoB, bile acids (BA), fibroblast growth factor 19 (FGF19), and cholecystokinin (CCK) were measured in post-absorptive conditions and over 4-h following the ingestion of a mixed test meal in a cross-sectional, pilot study involving 11 formerly obese female patients 33.8 ± 16.4 months after RYGB surgery and in 11 weight- and age-matched female control participants. RESULTS: Compared to controls, RYGB patients had faster (254 ± 14 vs. 327 ± 7 min, p < 0.05) and lower (0.14 ± 0.04 vs. 0.35 ± 0.07 mM, p < 0.05) peak TG responses, but their peak apoB48 responses tended to be higher (2692 ± 336 vs. 1841 ± 228 ng/ml, p = 0.09). Their postprandial total BA concentrations were significantly increased and peaked earlier after meal ingestion than in controls. Their FGF19 and CCK concentrations also peaked earlier and to a higher value. CONCLUSIONS: The early postprandial apoB48 and BA responses indicate that RYGB accelerated the rate of dietary lipid absorption. The lower postprandial peak TG strongly suggests that the RYGB simultaneously increased the clearance of TG-rich lipoproteins. CLINICAL TRIAL REGISTRATION: NCT01891591.

Characterization of hepatic fatty acids in mice with reduced liver fat by ultra-short echo time (1)H-MRS at 14.1 T in vivo.

Alterations in the hepatic lipid content (HLC) and fatty acid composition are associated with disruptions in whole body metabolism, both in humans and in rodent models, and can be non-invasively assessed by (1)H-MRS in vivo. We used (1)H-MRS to characterize the hepatic fatty-acyl chains of healthy mice and to follow changes caused by streptozotocin (STZ) injection. Using STEAM at 14.1 T with an ultra-short TE of 2.8 ms, confounding effects from T2 relaxation and J-coupling were avoided, allowing for accurate estimations of the contribution of unsaturated (UFA), saturated (SFA), mono-unsaturated (MUFA) and poly-unsaturated (PUFA) fatty-acyl chains, number of double bonds, PU bonds and mean chain length. Compared with in vivo (1) H-MRS, high resolution NMR performed in vitro in hepatic lipid extracts reported longer fatty-acyl chains (18 versus 15 carbons) with a lower contribution from UFA (61 ± 1% versus 80 ± 5%) but a higher number of PU bonds per UFA (1.39 ± 0.03 versus 0.58 ± 0.08), driven by the presence of membrane species in the extracts. STZ injection caused a decrease of HLC (from 1.7 ± 0.3% to 0.7 ± 0.1%), an increase in the contribution of SFA (from 21 ± 2% to 45 ± 6%) and a reduction of the mean length (from 15 to 13 carbons) of cytosolic fatty-acyl chains. In addition, SFAs were also likely to have increased in membrane lipids of STZ-induced diabetic mice, along with a decrease of the mean chain length. These studies show the applicability of (1)H-MRS in vivo to monitor changes in the composition of the hepatic fatty-acyl chains in mice even when they exhibit reduced HLC, pointing to the value of this methodology to evaluate lipid-lowering interventions in the scope of metabolic disorders.

Free Fatty Acids Impair FGF21 Action in HepG2 Cells.

BACKGROUND/AIMS: Fibroblast growth factor 21 (FGF21) is a key mediator of glucose and lipid metabolism. However, the beneficial effects of exogenous FGF21 administration are attenuated in obese animals and humans with elevated levels of circulating free fatty acids (FFA). METHODS: We investigated in vitro how FFA impact FGF21 effects on hepatic lipid metabolism. RESULTS: In the absence of FFA, FGF21 reduced lipogenesis and increased lipid oxidation in HepG2 cells. Inhibition of lipogenesis was associated with a down regulation of SREBP-1c, FAS and SCD1. The lipid-lowering effect was associated with AMPK and ACC phosphorylation, and up regulation of CPT-1α expression. Further, FGF21 treatment reduced TNFα gene expression, suggesting a beneficial action of FGF21 on inflammation. In contrast, the addition of FFA abolished the positive effects of FGF21 on lipid metabolism. CONCLUSION: In the absence of FFA, FGF21 improves lipid metabolism in HepG2 cells and reduces the inflammatory cytokine TNFα. However, under high levels of FFA, FGF21 action on lipid metabolism and TNFα gene expression is impaired. Therefore, FFA impair FGF21 action in HepG2 cells potentially through TNFα.

Protected maleimide building blocks for the decoration of peptides, peptoids and peptide nucleic acids

Monomers allowing for the introduction of [2,5-dimethylfuran]-protected maleimides into polyamides such as peptides, peptide nucleic acids, and peptoids were prepared, as well as the corresponding oligomers. Suitable maleimide deprotection conditions were established in each case. The stability of the adducts generated by Michael-type maleimide-thiol reaction and Diels-Alder cycloaddition to maleimide deprotection conditions was exploited to prepare a variety of conjugates from peptide and PNA scaffolds incorporating one free and one protected maleimide. The target molecules were synthesized by using two subsequent maleimide-involving click reactions separated by a maleimide deprotection step. Carrying out maleimide deprotection and conjugation simultaneously gave better results than performing the two reactions subsequently.

rDock: A Fast, Versatile and Open Source Program for Docking Ligands to Proteins and Nucleic Acids

Identification of chemical compounds with specific biological activities is an important step in both chemical biology and drug discovery. When the structure of the intended target is available, one approach is to use molecular docking programs to assess the chemical complementarity of small molecules with the target; such calculations provide a qualitative measure of affinity that can be used in virtual screening (VS) to rank order a list of compounds according to their potential to be active. rDock is a molecular docking program developed at Vernalis for high-throughput VS (HTVS) applications. Evolved from RiboDock, the program can be used against proteins and nucleic acids, is designed to be computationally very efficient and allows the user to incorporate additional constraints and information as a bias to guide docking. This article provides an overview of the program structure and features and compares rDock to two reference programs, AutoDock Vina (open source) and Schrodinger's Glide (commercial). In terms of computational speed for VS, rDock is faster than Vina and comparable to Glide. For binding mode prediction, rDock and Vina are superior to Glide. The VS performance of rDock is significantly better than Vina, but inferior to Glide for most systems unless pharmacophore constraints are used; in that case rDock and Glide are of equal performance. The program is released under the Lesser General Public License and is freely available for download, together with the manuals, example files and the complete test sets, at http://rdock.sourceforge.net/

Stabilization of the ionic form of weak acid cation exchange resins

Weak acid cation exchange (WAC) resins are used in the chromatographic separation of betaine from vinasse, a by-product of sugar industry. The ionic form of the resin determines the elution time of betaine. When a WAC-resin is in hydrogen form, the retention time of betaine is the longest and betaine elutes as the last component of vi-nasse from the chromatographic column. If the feed solution contains salts and its pH is not acidic enough to keep the resin undissociated, the ionic form of the hydrogen form resin starts to alter. Vinasse contains salts and its pH is around 5, it also contains weak acids. To keep the metal ion content (Na/H ratio) of the resin low enough to ensure successful separation of betaine, acid has to be added to either eluent (water) or vinasse. The aim of the present work was to examine by laboratory experiments which option requires less acid. Also the retention mechanism of betaine was investigated by measuring retention volumes of acetic acid and choline in different Na/H ratios of the resin. It was found that the resulting ionic form of the resin is the same regardless of whether the regeneration acid is added to the eluent or the feed solution (vinasse). Be-sides the salt concentration and the pH of vinasse, also the concentration of weak acids in the feed affects the resulting ionic form of the resin. The more buffering capacity vinasse has, the more acid is required to keep the ionic form of the resin desired. Vinasse was found to be quite strong buffer solution, which means relatively high amounts of acid are required to prevent the Na/H ratio from increasing too much. It is known that the retention volume of betaine decreases significantly, when the Na/H ratio increases. This is assumed to occur, because the amount of hydrogen bonds between the carboxylic groups of betaine and the resin decreases. Same behavior was not found with acetic acid. Choline has the same molecular structure as betaine, but instead of carboxylic group it has hydroxide group. The retention volume of choline increased as the Na/H ratio of the resin increased, because of the ion exchange reaction between choline cation and dissociated carboxylic group of the resin. Since the retention behavior of choline on the resin is opposite to the behavior of be-taine, the strong affinity of betaine towards hydrogen form WAC-resin has to be based on its carboxylic group. It is probable that the quaternary ammonium groups also affect the behavior of the carboxylic groups of betaine, causing them to form hydrogen bonds with the carboxylic groups of the resin.