Synthesis of enantiopure trans-N-Boc-3-aminobicyclo[2.2.2]octane-2-carboxylic acids and their bicyclic 1,3-amino alcohol derivatives via the [4+2] cycloaddition of 1,3-cyclohexadiene to a chiral β-nitroacrylate

The chiral β-nitroacrylate 2 derived from the (R)- or (S)-4-(3-hydroxy-4,4-dimethyl-2-oxopyrrolidin-1-yl) benzoic acid 1 acts as a reactive dienophile in a diastereoselective Diels-Alder reaction with 1,3-cyclohexadiene. The major cycloadducts have been isolated and transformed into enantiopure trans(2S,3S)- or (2R,3R)-N-Boc-3-aminobicyclic[2,2,2]octane-2-carboxylic acids 5. The trans-(2S,3S)- or (2R,3R)-N-Boc 3-(hydoxymethyl)-2-aminobicyclic[2,2,2]octane 6 derivatives were also obtained.     

Does Manganese Protect Cultured Human Skin Fibroblasts Against Oxidative Injury by Uva, Dithranol and Hydrogen Peroxide?

Reactive oxygen species (ROS) are involved in the mechanism of photoaging and carcinogenesis. Skin is endowed with antioxidant enzymes including superoxide dismutases (SOD): cytosolic copper zinc SOD and mitochondrial manganese SOD. The aim of our study was to estimate the protective effect of manganese against oxidative injury on cultured human skin fibroblasts. Dithranol, hydrogen peroxide and UV-A radiation (375 nm) were employed as oxidative stressors. The supply of manganese chloride produced an increase in cellular content of this element up to 24 fold without concomitant elevation of MnSOD activity. Nevertheless, manganese protects cells against two of the three ROS generating systems assessed, namely hydrogen peroxyde and UV-A. This protective effect depends on the concentration of manganese in the medium, 0.1 mM and 0.2 mM protect against UVA cytotoxicity, only 0.2 mM protects against H₂O₂ cytotoxicity.     

Modulation of the phase heterogeneity of aminoglycerophospholipid mixtures by sphingomyelin and monovalent cations: maintenance of the lamellar arrangement in the biological membranes

The phase behaviour of mixed molecular species of phosphatidylethanolamine, phosphatidylserine and sphingomyelin of biological origin were examined in aqueous co-dispersions using synchrotron X-ray diffraction. The co-dispersions of phospholipids studied were aimed to model the mixing of lipids populating the cytoplasmic and outer leaflets in the resting or scrambled activated cell membrane. Mixtures enriched with phosphatidylethanolamine and phosphatidylserine were characterized by a phase separation of non-lamellar phases (cubic and inverted hexagonal) with a lamellar gel phase comprising the most saturated molecular species. Inclusion of sphingomyelin in the mixture resulted in a suppression of the hexagonal-II phase in favour of lamellar phases at temperatures where a proportion of the phospholipid was fluid. The effect was also dependent on the total amount of sphingomyelin in ternary mixtures, and the lamellar phase dominated in mixtures containing more than 30 mol%, irrespective of the relative proportions of phosphatidylserine/sphingomyelin. A transition from gel to liquid-crystal phase was detected by wide-angle scattering during heating scans of ternary mixtures enriched in sphingomyelin and was shown by thermal cycling experiments to be coupled with a hexagonal-II phase to lamellar transition. In such samples there was evidence of a coexistence of non-lamellar phases with a lamellar gel phase. A transition of the gel phase to the fluid state on heating from 35 to 41 °C was evidenced by a progressive increase in the lamellar d-spacing. The presence of calcium enhanced the phase separation of a lamellar gel phase from a hexagonal-II phase in mixtures enriched in phosphatidylserine. This effect was counteracted by charge screening with 150 mM NaCl. The effect of sphingomyelin on stabilizing the lamellar phase is discussed in the context of an altered composition in the cytoplasmic/outer leaflets of the plasma membrane resulting from scrambling of the phospholipid distribution. The results suggest that a lamellar structure can be retained by the inward translocation of sphingomyelin in biological membranes. The presence of monovalent cations serves also to stabilize the bilayer in activated cells where a translocation of aminoglycerophospholipids and an influx of calcium occur simultaneously.Abbreviations PC phosphatidylcholine - PE phosphatidylethanolamine - PS phosphatidylserine - SAXS small-angle X-ray scattering - SM sphingomyelin - WAXS wide-angle X-ray scattering - XRD X-ray diffraction     

Halimeda contribution to organic and inorganic production in a Tahitian reef system

Of the seven species of Halimeda inhabiting a lagoon on Moorea island, three representing 10% of the algal covering and averaging 111 g of dry weight m^-2, have been studied in the course of a year. The biomass, measured bimonthly, stresses a slight seasonal variability in the species life. The main decrease was reported for H. opuntia after a fruiting event, which happened in October. The primary production was assessed, in situ, periodically over a year, by measuring oxygen variations in enclosures. Either expressed on specific-weight basis or in area units, the highest primary productions were recorded for H. opuntia. Productions and biomasses vary simultaneously during the year. The three species produce all together about 6 g C m^-2y^-1. The growth rate of the sand-dwelling H. incrassata f. ovata was followed during the year by staining, in the field, individuals with alizarin Red-S. The average rates measured were 3.3 segments ind^-1d^-1 and 0.17 gdw d^-1m^-2. The contribution of the three species to the carbonate budget of the reef was estimated by total alkalinity measurements during 24-h cycles. H. opuntia had the highest CaCO₃ production. For the three species studied, CaCO₃ production of 1.4 kg m^-2y^-1, which could correspond to a 0.4mm/year accretion of the studied reefal system, was estimated.     

FRET or no FRET: a quantitative comparison

Fluorescence resonance energy transfer (FRET) is a technique used to measure the interaction between two molecules labeled with two different fluorophores (the donor and the acceptor) by the transfer of energy from the excited donor to the acceptor. In biological applications, this technique has become popular to qualitatively map protein-protein interactions, and in biophysical projects it is used as a quantitative measure for distances between a single donor and acceptor molecule. Numerous approaches can be found in the literature to quantify and map FRET, but the measures they provide are often difficult to interpret. We propose here a quantitative comparison of these methods by using a surface FRET system with controlled amounts of donor and acceptor fluorophores and controlled distances between them. We support the system with a Monte Carlo simulation of FRET, which provides reference values for the FRET efficiency under various experimental conditions. We validate a representative set of FRET efficiencies and indices calculated from the different methods with different experimental settings. Finally, we test their sensitivity and draw conclusions for the preparation of FRET experiments in more complex and less-controlled systems.     

MANAGEMENT OF UPPER GASTROINTESTINAL HEMORRHAGE

In the past few years gastric resection has become the therapy of choice for patients with massive hemorrhage from duodenal ulcer. When this is done as an emergency procedure the ability of the surgeon is often taxed to the limit. Although sometimes easy, control is often extraordinarily difficult. Many important technical details must be considered in order to attain a successful outcome. This method of therapy has proved to be very satisfactory with patients who are in good condition for operation, and even in the poorer risks seen on ward service has resulted in a surgical mortality of only 7 per cent in all patients less than 60 years of age treated for this extremely severe type of hemorrhage. In the older age groups mortality rates still remain high.