Structure-Activity Relationship Explorations and Discovery of a Potent Antagonist for the Free Fatty Acid Receptor 2

Free fatty acid receptor 2 (FFA2) is a sensor for short-chain fatty acids that has been identified as an interesting potential drug target for treatment of metabolic and inflammatory diseases. Although several ligand series are known for the receptor, there is still a need for improved compounds. One of the most potent and frequently used antagonists is the amide-substituted phenylbutanoic acid known as CATPB ( 1 ). We here report the structure-activity relationship exploration of this compound, leading to the identification of homologues with increased potency. The preferred compound 37 (TUG-1958) was found, besides improved potency, to have high solubility and favorable pharmacokinetic properties.     

Subcellular Localization of Acyl-CoA: Lysophosphatidylethanolamine Acyltransferases (LPEATs) and the Effects of Knocking-Out and Overexpression of Their Genes on Autophagy Markers Level and Life Span of A. thaliana

Arabidopsis thaliana possesses two acyl-CoA:lysophosphatidylethanolamine acyltransferases, LPEAT1 and LPEAT2, which are encoded by At1g80950 and At2g45670 genes, respectively. Both single lpeat2 mutant and double lpeat1 lpeat2 mutant plants exhibit a variety of conspicuous phenotypes, including dwarfed growth. Confocal microscopic analysis of tobacco suspension-cultured cells transiently transformed with green fluorescent protein-tagged versions of LPEAT1 or LPEAT2 revealed that LPEAT1 is localized to the endoplasmic reticulum (ER), whereas LPEAT2 is localized to both Golgi and late endosomes. Considering that the primary product of the reaction catalyzed by LPEATs is phosphatidylethanolamine, which is known to be covalently conjugated with autophagy-related protein ATG8 during a key step of the formation of autophagosomes, we investigated the requirements for LPEATs to engage in autophagic activity in Arabidopsis. Knocking out of either or both LPEAT genes led to enhanced accumulation of the autophagic adaptor protein NBR1 and decreased levels of both ATG8a mRNA and total ATG8 protein. Moreover, we detected significantly fewer membrane objects in the vacuoles of lpeat1 lpeat2 double mutant mesophyll cells than in vacuoles of control plants. However, contrary to what has been reported on autophagy deficient plants, the lpeat mutants displayed a prolonged life span compared to wild type, including delayed senescence.     

A mechanistic study of electrodeposition of bismuth telluride on stainless steel substrates

Miniaturization of Bi₂Te₃ compounds is of great interest in semiconductor industries due to their distinct anisotropic thermoelectric properties at room temperature. The aim of the present work was to investigate the mechanism of the electrodeposition of Bi₂Te₃ compounds on stainless steel substrates and relate the morphology and composition of the resulting deposits to experimental parameters. Cyclic voltammetry (CV) experiments in acidic solutions containing Bi³⁺ and/or HTeO₂⁺ ions show that the deposition potential for the Bi₂Te₃ compound is more positive than either of the single elements alone. A detailed mechanism of the co-deposition was obtained by varying the concentrations of the two elements and evaluating the corresponding morphological and compositional changes of the deposits. The results show that the deposition of Te is kinetically hindered and that Bi deposition plays a major role during the co-deposition.     

Exposure to diesel exhaust induces changes in EEG in human volunteers

Background  

Ambient particulate matter and nanoparticles have been shown to translocate to the brain, and potentially influence the central nervous system. No data are available whether this may lead to functional changes in the brain.     

Modelling and simulation of local mechanical properties of high silicon solution-strengthened ferritic compacted graphite iron

This study focuses on the modelling and simulation of local mechanical properties of compacted graphite iron cast at different section thicknesses and three different levels of silicon, ranging from about 3.6% up to 4.6%. The relationship between tensile properties and microstructure is investigated using microstructural analysis and statistical evaluation. Models are generated using response surface methodology, which reveal that silicon level and nodularity mainly affect tensile strength and 0.2% offset yield strength, while Young′s modulus is primarily affected by nodularity. Increase in Si content improves both the yield and tensile strength, while reduces elongation to failure. Furthermore, mechanical properties enhance substantially in thinner section due to the high nodularity. The obtained models have been implemented into a casting process simulation, which enables prediction of local mechanical properties of castings with complex geometries. Very good agreement is observed between the measured and predicted microstructures and mechanical properties, particularly for thinner sections.     

ESR studies of the effect of zeolite structures on motional dynamics of NO2

Electron spin resonance (ESR) spectroscopy was used to study the effect of zeolite structure on the motional dynamics of NO₂ adsorbed on the zeolites. The temperature-dependent ESR spectral line shapes were quantitatively analyzed using the slow-motion ESR theory. It was observed that the motional dynamics of NO₂ is strongly dependent on the structure of the zeolite (Beta-type, ZSM-5, mordenite, L-type and ferrierite zeolites). The following important observations were made. (1) In zeolites with similar channel structures, the diffusion rate of NO₂ is proportional to the channel size, and the order of the diffusion rates is Beta-type>ZSM-5>ferrierite and L-type>mordenite. (2) The diffusion of NO₂ is faster in the zeolites with multi-dimensional channels (Beta-type, ZSM-5 and ferrierite) than that in those with uni-dimensional channels (L-type and mordenite).     

Temporal trends of synthetic musk compounds in mother's milk and associations with personal use of perfumed products

We analyzed two nitro musks (musk xylene and musk ketone) and five polycyclic musks (HHCB, AHTN, ADBI, ATII, and AHDI) in mother's milk from primiparae women (N = 101) living in Uppsala County, Sweden, 1996-2003. Possible temporal trends in musk concentrations and associations with lifestyle/medical factors, such as use of perfumed products during pregnancy were studied. HHCB showed the highest median concentration (63.9 ng/g lipid) followed by AHTN (10.4 ng/g) and musk xylene (MX) (9.5 ng/g). Concentrations of the other substances were, in most cases, below the quantification limit (2.0-3.0 ng/g). Women with a high use of perfume during pregnancy had elevated milk concentrations of HHCB, and elevated concentrations of AHTN were observed among women reporting use of perfumed laundry detergent. This strongly suggests that perfumed products are important sources of musk exposure both among the mothers and the nursed infants. Concentrations of AHTN and MX declined significantly between 1996 and 2003, suggesting a decline in the industrial use of the compounds in consumer products, or alterations in the consumer use pattern of perfumed products. No temporal trend in HHCB concentrations was seen. The lack of toxicity data makes it difficult to generalize about the safety of musk exposure of breast-fed infants.     

Selection of phytate-degrading human bifidobacteria and application in whole wheat dough fermentation

Lately, whole wheat products are highly recommended from their healthy properties. However, the presence of phytic acid (InsP(6)) could partly limit their benefits because it decreases the mineral bioavailability due to its chelating properties. The objective of this work was to select strains with high phytate-degrading activity from human feces, and evaluate their suitability for the bread making process. Twenty-three different bifidobacterial strains (13 from infants and 10 from adults) were isolated, belonging to the species Bifidobacterium longum, Bifidobacterium breve and Bifidobacterium catenulatum. The phosphatase and phytase activities of these strains were evaluated as well as their ability to degrade InsP(6) during growth. Then, the fermentative ability of the strain showing the highest phytate-degrading activity (B. longum. BIF307) was determined in whole wheat breadmaking. The use of the selected bifidobacterial strain as starter during whole wheat fermentation resulted in bread with similar technological quality than the control (in absence of bifidobacteria) and crumb with lower levels of inositol phosphates. Therefore, the used of the selected Bifidobacterium strain in whole wheat breadmaking process could provide potential nutritional benefits by decreasing the antinutrient content of the product.     

Conditions for aggregation of CHP plants in the UK electricity market and exploration of plant size

Combined heat and power (CHP) plants with thermal stores may be suitable for sustainable energy production and the accommodation of fluctuating renewable energy sources. At the moment, in the UK, only a few CHP plants have thermal stores. Previous research has shown that thermal stores can improve the economics of CHP plants in the UK under the current market conditions. However, currently, it is only beneficial for CHP plants to sell their electricity to a third party, a Licensed Electricity Supplier, rather than to sell it directly to the power exchange market at prices which are much higher. If CHP plants aggregate, direct access to the power exchange market can become economically viable hence there is the possibility that thermal stores could further improve the economics of CHP plants under an aggregated electricity dispatch. This work firstly explains the conditions under which such plants could aggregate and act as a large power plant in the UK market, and secondly explores the most economic-size of gas engine and thermal store, in the case of aggregation, using energyPRO software and Excel spreadsheets. The work suggests that direct access to the power exchange market can improve the economics of the CHP plants. The highest Net Present Value (NPV), without heat dissipation, for a CHP plant exporting its electricity to the grid for a community heating load of 20 GW h, is more than £5 m, and is obtained for a 6 MW engine with a 28.2 MW h (900 m³) thermal store. The research suggests that such high electricity prices could make even larger plants more profitable than that; however, this can happen only if some of the produced heat is dissipated.