Effect of Glutathione and N-Acetylcysteine on in Vitro and in VIVO Cardiac Toxicity of Doxorubicin

The effects of two sulfhydryl compounds, glutathione (GSH) and N-acetylcysteine (NAC), on the cardiotoxicity of doxorubicin (DXR) were tested on in vitro and in vivo models. DXR was administered to rats as 4 weekly i.v. doses of 3mg/kg. GSH (1.5 mmoles/kg), given i.v. 10 min before and 1 hr after DXR, was found to prevent the development of the delayed cardiotoxic effects of DXR, as assessed by electrocardiographic and mechanical parameters, as well as by histological examination of left ventricular preparations. In contrast, equimolar oral doses of NAC (1 hr before and 2hrs after DXR) were found to be ineffective. Both GSH and NAC prevented the negative inotropic effect produced by DXR on isolated rat atria. A good correlation exists between the cardioprotective effects of the two agents and their ability to enhance the non-protein sulfhydryl group content of the myocardium. Differences observed in vivo between GSH and NAC might be accounted for by pharmacokinetic factors.     

Water stress,temperature, and light effects on the capacity for isoprene emission and photosynthesis of kudzu leaves

Kudzu (Pueraria lobata (Willd) Ohwi.) is a vine which forms large, monospecific stands in disturbed areas of the southeastern United States. Kudzu also emits isoprene, a hydrocarbon which can significantly affect atmospheric chemistry including reactions leading to tropospheric ozone. We have studied physiological aspects of isoprene emission from kudzu so the ecological consequences of isoprene emission can be better understood. We examined: (a) the development of isoprene emission as leaves developed, (b) the interaction between photon flux density and temperature effects on isoprene emission, (c) isoprene emission during and after water stress, and (d) the induction of isoprene emission from leaves grown at low temperature by water stress or elevated temperature. Isoprene emission under standard conditions of 1000 mol photons·m^-2·s^-1 and 30°C developed only after the leaf had reached full expansion, and was not complete until up to two weeks past the point of full expansion of the leaf. The effect of temperature on isoprene emission was much greater than found for other species, with a 10°C increase in temperature causing a eight-fold increase in the rate of isoprene emission. Isoprene emission from kudzu was stimulated by increases in photon flux density up to 3000 mol photons·m^-2·s^-1. In contrast, photosynthesis of kudzu was saturated at less than 1000 mol·m^-2·s^-1 photon flux density and was reduced at high temperature, so that up to 20% of the carbon fixed in photosynthesis was reemitted as isoprene gas at 1000 mol photons·m^-2·s^-1 and 35°C. Withholding water caused photosynthesis to decline nearly to zero after several days but had a much smaller effect on isoprene emission. Following the relief of water stress, photosynthesis recovered to the prestress level but isoprene emission increased to about five times the prestress rate. At 1000 mol photons·m^-2·s^-1 and 35°C as much as 67% of the carbon fixed in photosynthesis was reemitted as isoprene eight days after water stress. Leaves grown at less than 20°C did not make isoprene until an inductive treatment was given. Inductive treatments included growth at 24°C, leaf temperature of 30°C for 5 h, or witholding water from plants. With the new information on temperature and water stress effects on isoprene emission, we speculate that isoprene emission may help plants cope with stressful conditions.     

Polymorphic tandem repeat region in interleukin-1α intron 6

Analysis of polymerase chain reaction amplified products from the sixth intron of the human interleukin-1 gene reveals a high polymorphism (polymorphism information content = 0.51) in a Caucasian population. Altogether, seven alleles have been defined ranging from 620 to 1220bp. This polymorphism is probably attributable to a variable number of 46-bp tandem repeats, each containing potential regulatory sequences.     

Fine-scale mapping of physicochemical and microbial landscapes of the coral skeleton

The coral skeleton harbours a diverse community of bacteria and microeukaryotes exposed to light, O₂ and pH gradients, but how such physicochemical gradients affect the coral skeleton microbiome remains unclear. In this study, we employed chemical imaging of O₂ and pH, hyperspectral reflectance imaging and spatially resolved taxonomic and inferred functional microbiome characterization to explore links between the skeleton microenvironment and microbiome in the reef-building corals Porites lutea and Paragoniastrea benhami. The physicochemical environment was more stable in the deep skeleton, and the diversity and evenness of the bacterial community increased with skeletal depth, suggesting that the microbiome was stratified along the physicochemical gradients. The bulk of the coral skeleton was in a low O₂ habitat, whereas pH varied from pH 6–9 with depth. Physicochemical gradients of O₂ and pH of the coral skeleton explained the β-diversity of the bacterial communities, and skeletal layers that showed O₂ peaks had a higher relative abundance of endolithic algae, reflecting a link between the abiotic environment and the microbiome composition. Our study links the physicochemical, microbial and functional landscapes of the coral skeleton and provides new insights into the involvement of skeletal microbes in the coral holobiont metabolism.     

The mlo resistance alleles to powdery mildew infection in barley trigger a developmentally controlled defence mimic phenotype

Recessive mlo resistance alleles of the Mlo locus in barley control a non race-specific resistance response to infection by the obligate biotrophic fungus Erysiphe graminis f.sp. hordei. All the mlo alleles analysed stop fungal growth at the same developmental stage within a subcellularly restricted, highly localized cell wall apposition directly beneath the site of abortive fungal penetration. We report that near-isogenic lines carrying the alleles mlo ₁, mlo ₃ or mlo ₅ undergo dramatic spontaneous formation of cell wall appositions, not only in the absence of the fungal pathogen but also in sterile grown plants. A comparative study of spontaneous and infection-triggered cell wall appositions reveals a high degree of similarity with respect to structure, chemical composition and distinct localization within plant tissue. We show that the rate of spontaneous apposition formation is dependent on the genetic background of the plant and that its onset is under developmental control. Furthermore, spontaneous formation of wall appositions is specifically triggered by mlo alleles, since it is unaffected in the presence of the race-specific resistance allele Mlg. We propose a model for the function of the Mlo locus that suggests that both Mlo and mlo alleles control qualitatively the same apposition-based resistance mechanism, which, in the presence of the wild-type Mlo allele, is merely less efficient to provide protection against the currently common races of E. graminis f.sp. hordei.     

Facile reduction of peptide oxime endothelin antagonist during trialkylsilane/TFA cleavage after solid-phase synthesis

Summary We describe a new solid-phase strategy for the selective reduction of the C=N bond in peptide oximes using a trialkylsilane in trifluoroacetic acid. The reduction is performed directly on the resin-bound peptide, with concomitant cleavage of the peptide from the resin and deblocking of protected side chains.     

Genetic differentiation and detection of cryptic species in the genus Lepismachilis (Insecta: Microcoryphia) from the Western Mediterranean region

Different species of the bristletail genus Lepismachilis were collected in 14 localities in Italy and Spain and an allozyme electrophoretic survey was carried out to estimate the degree of genetic variability and differentiation at intra- and interspecific levels. Four morphological species were initially identified (L osellai, L. y-signata, L. affinis, L. targionii), but the electrophoretic analysis demonstrated the presence of two additional species among the individuals of L. targionii (Lepismachilis spl and sp2). The validity of these species and their differentiation from L targionii were demonstrated by the fixation of alternative allelic patterns at several loci (7 in Lepismachilis spl and 8 in Lepismachilis sp2), coupled with fixed, previously undetected, morphological differences. In addition, Lepismachilis sp2 was sympatric with L. targionii in three collecting sites, where the fixation of alternative allelic patterns unequivocally demonstrated reproductive isolation. Genetic variability did not seem to be correlated with local ecological factors, and differences between species should rather be explained by different historical factors. Low levels of gene flow, estimated with two different indirect methods, were observed in L. targionii and L. y-signata, and were due to high levels of structuring among populations. Genetic differentiation among conspecific populations was not correlated to their geographical arrangement and the presence of loci fixed for different alleles among them suggested that stochastic factors (such as genetic drift) may have played a role in determining genetic differentiation of geographically isolated populations. Genetic divergence values indicated that the six species are well differentiated and allozyme profiles were diagnostic for all of them. On the other hand, allozyme data did not provide adequate information to resolve evolutionary relationships among the species, nor did they confirm the validity of the two subgenera (Lepismachilis and Berlesilis) in which the genus Lepismachilis is traditionally divided.     

Sterols from three Lactarius species

The sterol composition of three fungi was determined. Ergosterol is the major sterol, accompanied by other closely related sterols.