How do sterols determine the antifungal activity of amphotericin B? Free energy of binding between the drug and its membrane targets

Amphotericin B (AmB) is a well-known polyene antibiotic used to treat systemic fungal infections. It is commonly accepted that the presence of sterols in the membrane is essential for the AmB biological activity, that is, for the formation of transmembrane ion channels. The selective toxicity of AmB for fungal cells is attributed to the fact that it is more potent against fungal cell membranes containing ergosterol than against the mammalian membranes with cholesterol. According to the "primary complex" hypothesis, AmB associates with sterols in a membrane to form binary complexes, which may subsequently assemble into a barrel-stave channel. To elucidate the molecular nature of the AmB selectivity for ergosterol-containing membranes, in the present work, we used computational methods to study the formation of the putative AmB/sterol complexes in a lipid bilayer. The free energy profiles for the AmB-sterol association in phospholipid bilayers containing 30 mol % of sterols were calculated and thoroughly analyzed. The results obtained confirm the formation of specific AmB/ergosterol complexes and are used to determine the energetic and structural origin of the enhanced affinity of AmB for ergosterol than for cholesterol. The significance of this affinity difference for the mechanism of action of AmB is discussed. The data obtained allowed us also to suggest a possible origin of the increased selectivity of a novel class of less toxic AmB derivatives.     

Screening of transformation products in soils contaminated with unsymmetrical dimethylhydrazine using headspace SPME and GC-MS

The paper describes a novel SPME-based approach for sampling and analysis of transformation products of highly reactive and toxic unsymmetrical dimethylhydrazine (UDMH) which is used as a fuel in many Russian, European, Indian, and Chinese heavy cargo carrier rockets. The effects of several parameters were studied to optimize analyte recovery. It was found that the 85 μm Carboxen/polydimethylsiloxane fiber coating provides the highest selectivity for selected UDMH transformation products. Optimal sampling/sample preparation parameters were determined to be 1-h soil headspace sampling time at 40 °C. The GC inlet temperature was optimized to 170 °C held for 0.1 min, then 1 °C s⁻¹ ramp to 250 °C where it was held for 40 min. Temperature programing resulted in a fast desorption along with minimal chemical transformation in the GC inlet. SPME was very effective extracting UDMH transformation products from soil samples contaminated with rocket fuel. The use of SPME resulted in high sensitivity, speed, small labor consumption due to an automation and simplicity of use. It was shown that water addition to soil leads to a significant decrease of recovery of almost all target transformation products of UDMH. The use of SPME for sampling and sample preparation resulted in detection of the total of 21 new compounds that are relevant to the UDMH transformation in soils. In addition, the number of confirmed transformation products of UDMH increased from 15 to 27. This sampling/sample preparation approach can be recommended for environmental assessment of soil samples from areas affected by space rocket activity.     

Dimension and measure for semi-hyperbolic rational maps of degree 2

We prove that almost every non-hyperbolic rational map of degree 2 has at least one recurrent critical point. This estimate is optimal because the set of rational maps with all critical points non-recurrent is of full Hausdorff dimension. To cite this article: M. Aspenberg, J. Graczyk, C. R. Acad. Sci. Paris, Ser. I 347 (2009).     

Around Browder’s fixed point theorem for contractions

We revisit a fixed point theorem for contractions established by Felix Browder in 1968. We show that many definitions of contractive mappings which appeared in the literature after 1968 turn out to be equivalent formulations or even particular cases of Browder’s definition. We also discuss the problem of the existence of approximate fixed points of continuous mappings; in particular, we settle it in the affirmative for Browder contractions. Finally, we recall three problems concerning Browder contractions which remain unsolved. With great respect for Professor Felix E. Browder     

Crystal and supramolecular structures of dioxomolybdenum(VI) and dioxotungsten(VI) complexes of dihydroxybenzoic acids

The tetramethylammonium salts (NMe₄)₂[MO₂(2,3-Hdhb)₂]·2H₂O and (NMe₄)₂[MO₂(3,4-Hdhb)₂]·6H₂O (M = Mo, W; Hdhb = monoprotonated form of 2,3- or 3,4-dihydroxybenzoic acid, 2,3-H₃dhb or 3,4-H₃dhb) were prepared and their crystal structures determined. The structure of [Mg(H₂O)₆](NMe₄)₄[MoO₂(3,4-dhb)(3,4-Hdhb)]₂·13H₂O, obtained by the recrystallization of (NMe₄)₂[MoO₂(3,4-Hdhb)₂] in the presence of magnesium ions, is also reported. The supramolecular interactions of the five structures are discussed in detail concerning the hydrogen bonding patterns involving complexes and water molecules of crystallization.     

Current trends in solid-phase microextraction (SPME) fibre coatings

This critical review presents information on known and innovative approaches to the manufacture of fibre coatings used in solid-phase microextraction (SPME). The properties, advantages and drawbacks of the different types of commercially available SPME fibre coatings are discussed in detail, as are those of novel types of coatings and the methodologies of their preparation. The applications of fibre coatings in the solid-phase microextraction of a broad spectrum of analytes are analysed, with particular emphasis on the sampling of polar analytes from polar matrices (174 references).     

Kinetics of Interfacial Polycondensation of Bisphenols with Isophthaloyl Chloride

Reaction rates of interfacial polycondensation of bisphenol A and chlorobisphenol II with isophthaloyl chloride were investigated. Rate constants and activation energies were determined The reaction rate was found to depend on stirring speed, catalyst, type of bisphenol, and temperature.