Imaging cytoplasmic cAMP in mouse brainstem neurons

Background  

cAMP is an ubiquitous second messenger mediating various neuronal functions, often as a consequence of increased intracellular Ca²⁺ levels. While imaging of calcium is commonly used in neuroscience applications, probing for cAMP levels has not yet been performed in living vertebrate neuronal tissue before.     

A simple model for a two-stage chemical reaction with diffusion

We analyse the evolution of a two-stage chemical reaction betweentwo neighbouring plumes of reactants. Under the assumption thatthe plumes are approximately Gaussian we derive a system ofordinary differential equations for the total amount, the centroidand the variance of each reactant. We compare the solution ofthese equations with full numerical simulation of the reaction.Excellent agreement is obtained, with solution of the near-Gaussianmodel requiring considerably less computational effort thanthe full simulations. Of key importance is the yield of thereaction, and we discuss this feature in particular.     

FATTY ACID ANALYSIS AS A FUNCTION OF PHOTO-OXIDATION IN EGG YOLK LECITHIN VESICLES

Abstract— The photo-oxidation by O₂(¹Δ_g) of individual lipid components in egg yolk lecithin is examined as a function of time. The rate of oxidation is correlated with the degree of unsaturation in the fatty-acid chains.     

Synthesis of sparteine-like chiral diamines and evaluation in the enantioselective lithiation-substitution of N-(tert-butoxycarbonyl)pyrrolidine

Three chiral diamines were synthesised and evaluated as sparteine surrogates in the lithiation-substitution of N-(tert-butoxycarbonyl)pyrrolidine. The synthesis and attempted resolution of sparteine-like diamines [(1S*,2R*,8R*)-10-methyl-6,10-diazatricyclo[6.3.1.0(2,6)]dodecane and (1S*,2R*,9R*)-11-methyl-7,11-diazatricyclo[7.3.1.0(2,7)]tridecane] (via inclusion complex formation) are reported. Unfortunately, it was only possible to resolve the diazatricyclo[7.3.1.0(2,7)]tridecane compound. An alternative route to (1R,2S,9S)-11-methyl-7,11-diazatricyclo[7.3.1.0(2,7)]tridecane starting from the natural product, (-)-cytisine, is described. This simple three-step route furnished gram-quantities of a (+)-sparteine surrogate. X-Ray crystallography of an intermediate in the route, (1R,5S,12S)-3-methoxycarbonyldecahydro-1,5-methanopyrido[1,2-a][1,5]diazocin-8-one, enabled the stereochemistry of all of the tricyclic diamines described in this paper to be unequivocally established. Two other diamines, starting from (S)-proline and resolved 2-piperidine ethanol, were prepared using standard methods. These diamines lacked the bispidine framework of (-)-sparteine and were found to impart vastly inferior enantioselectivity. It was concluded that, for the asymmetric lithiation substitution of N-Boc pyrrolidine, a rigid bispidine framework and only three of the four rings of (-)-sparteine are needed for high enantioselectivity. Furthermore, it is shown that diamine (1R,2S,9S)-11-methyl-7,11-diazatricyclo[7.3.1.0(2,7)]tridecane is the first successful (+)-sparteine surrogate.     

How not to develop a quantitative structure–activity or structure–property relationship (QSAR/QSPR)

Although thousands of quantitative structure–activity and structure–property relationships (QSARs/QSPRs) have been published, as well as numerous papers on the correct procedures for QSAR/QSPR analysis, many analyses are still carried out incorrectly, or in a less than satisfactory manner. We have identified 21 types of error that continue to be perpetrated in the QSAR/QSPR literature, and each of these is discussed, with examples (including some of our own). Where appropriate, we make recommendations for avoiding errors and for improving and enhancing QSAR/QSPR analyses.