An HPLC‐ECD method for monoamines and metabolites quantification in cuttlefish (cephalopod) brain tissue

The cuttlefish belongs to the mollusk class Cephalopoda, considered as the most advanced marine invertebrates and thus widely used as models to study the biology of complex behaviors and cognition, as well as their related neurochemical mechanisms. Surprisingly, methods to quantify the biogenic monoamines and their metabolites in cuttlefish brain remain sparse and measure a limited number of analytes. This work aims to validate an HPLC‐ECD method for the simultaneous quantification of dopamine, serotonin, norepinephrine and their main metabolites in cuttlefish brain. In comparison and in order to develop a method suitable to answer both ecological and biomedical questions, the validation was also carried out on a phylogenetically remote species: mouse (mammals). The method was shown to be accurate, precise, selective, repeatable and sensitive over a wide range of concentrations for 5‐hydroxyindole‐3‐acetic acid, serotonin, dopamine, 3,4‐dihydroxyphenylacetic acid and norepinephrine in the both extracts of cuttlefish and mouse brain, though with low precision and recovery for 4‐hydroxy‐3‐methoxyphenylethylene glycol. Homovanillic acid, accurately studied in rodents, was not detectable in the brain of cuttlefish. Overall, we described here the first fully validated HPLC method for the routine measurement of both monoamines and metabolites in cuttlefish brain. Copyright © 2016 John Wiley & Sons, Ltd.     

The challenge in managing new financial risks: adopting an heuristic or theoretical approach

The financial crisis began with the collapse of Lehman Brothers and the subprime asset backed securities debacle. Credit risk was turned into liquidity risk, resulting in a lack of confidence among financial institutions. In this article, we will propose a way to model liquidity risk and the credit risk in best practices. We will show that liquidity risk is a new type of risk and the current way to deal with it is based solely on observed variables without any theoretical link. We propose an heuristic approach to combine the numerous liquidity risk indicators with a logistic regression for the first time. In regards to credit risk, several articles prove that the best practice is to use an option model to appreciate this risk. We will present our methodology using stochastic diffusion for the interest rate because currently the yield curves aren’t liquid. This approach is more relevant because the basis model in prior publications has a constant interest rate or a forward rate. Both models allow a better understanding of liquidity and credit risks and the further development of research deals with the link between these two financial risks.     

CAESAR models for developmental toxicity

Background

The new REACH legislation requires assessment of a large number of chemicals in the European market for several endpoints. Developmental toxicity is one of the most difficult endpoints to assess, on account of the complexity, length and costs of experiments. Following the encouragement of QSAR (in silico) methods provided in the REACH itself, the CAESAR project has developed several models.

Results

Two QSAR models for developmental toxicity have been developed, using different statistical/mathematical methods. Both models performed well. The first makes a classification based on a random forest algorithm, while the second is based on an adaptive fuzzy partition algorithm. The first model has been implemented and inserted into the CAESAR on-line application, which is java-based software that allows everyone to freely use the models.

Conclusions

The CAESAR QSAR models have been developed with the aim to minimize false negatives in order to make them more usable for REACH. The CAESAR on-line application ensures that both industry and regulators can easily access and use the developmental toxicity model (as well as the models for the other four endpoints).

     

Global QSAR models of skin sensitisers for regulatory purposes

Background

The new European Regulation on chemical safety, REACH, (Registration, Evaluation, Authorisation and Restriction of CHemical substances), is in the process of being implemented. Many chemicals used in industry require additional testing to comply with the REACH regulations. At the same time EU member states are attempting to reduce the number of animals used in experiments under the 3 Rs policy, (refining, reducing, and replacing the use of animals in laboratory procedures). Computational techniques such as QSAR have the potential to offer an alternative for generating REACH data. The FP6 project CAESAR was aimed at developing QSAR models for 5 key toxicological endpoints of which skin sensitisation was one.

Results

This paper reports the development of two global QSAR models using two different computational approaches, which contribute to the hybrid model freely available online.

Conclusions

The QSAR models for assessing skin sensitisation have been developed and tested under stringent quality criteria to fulfil the principles laid down by the OECD. The final models, accessible from CAESAR website, offer a robust and reliable method of assessing skin sensitisation for regulatory use.

     

Controlled pinewood fractionation with supercritical ethanol: A prerequisite toward pinewood conversion into chemicals and biofuels

The objective of this work was to investigate the ability of supercritical (SC) ethanol conditions to attack preferentially the lignin fraction against the carbohydrate fraction and their effects on the product distribution among gases, light products, bio-oils, and chars. In this study, the conversion of each pinewood component was determined by the analysis of solid residues to quantify cellulose, hemicellulose, lignin, and char contents. It is shown that, by tuning the temperature, hemicellulose and lignin are already transformed in subcritical ethanol conditions, lignin being more reactive than hemicellulose. In contrast, native wood cellulose is recalcitrant to liquefaction in SC ethanol near the critical point (T_c = 241 °C and P_c = 61 bar), but 20% of native wood cellulose is converted in SC ethanol at 280 °C. Besides, the severity of the conditions, in terms of temperature and treatment time, does not significantly influence the yields of gases, light products, and bio-oils but strongly enhances char formation. Interestingly, the increase in SC ethanol density does not change the conversion of biomass components but has a marked effect on bio-oil yield and prevents char formation. The optimum fractionation conditions to convert the lignin component, while keeping unattacked the cellulose fraction with a minimum formation of char, are dense SC ethanol, at 250 °C for 1 h, in batch conditions. However, although lignin is more reactive than hemicellulose under these conditions, these fractions are converted, in a parallel way, to around 50% and 60%, respectively.     

Direct C-glycosylation by indium-mediated alkynylation on sugar anomeric position

Indium-mediated alkynylation reaction was studied for the direct preparation of C-glycosides. Easily available starting sugar derivatives with an acetyl group at the anomeric position were tested as electrophiles toward alkynylindium reagents under Barbier conditions. Good yields and stereoselectivities were observed during the reaction. The alkynylation was applied to the synthesis of an alpha-(1-->6)-C-disaccharide analogue of isomaltoside.     

Remarkably efficient synthesis of 2H-indazole 1-oxides and 2H-indazoles via tandem carbon-carbon followed by nitrogen-nitrogen bond formation

Base-catalyzed tandem carbon-carbon followed by nitrogen-nitrogen bond formations quantitatively converted N-alkyl-2-nitro-N-(2-oxo-2-aryl-ethyl)-benzenesulfonamides to 2H-indazoles 1-oxides under mild conditions. Triphenylphosphine or mesyl chloride/triethylamine-mediated deoxygenation afforded 2H-indazoles.     

Emulsion stabilization and inversion using a pH- and temperature-sensitive amphiphilic copolymer

We describe how a versatile amphiphilic diblock copolymer can form oil-in-water (o/w) or water-in-oil (w/o) emulsions depending on pH and temperature. At high pH and temperature, this copolymer is mostly hydrophobic and forms w/o emulsions. Its spontaneous curvature is greatly increased upon pH and/or temperature lowering (due to protonation and/or hydration, respectively), which allows the formation of o/w emulsions. Conductivity measurements and confocal fluorescence micrographs evidence the two kinds of structures obtained over a wide range of pH and temperature. We also show how the emulsion type can be reversibly switched along a temperature scan under stirring. The lower stability of the w/o emulsions as compared to the o/w ones is attributed to a lack of electrostatic repulsion. The importance of the copolymer architecture and conformation with regards to droplet stability is discussed.