Chemical dichotomies in the Magnolialean complex

The most characteristic chemosystematic feature of the Magnolialean families (here delineated to include the Magnoliiflorae plus Piperales in the sense of Dahlgren, 1983) is the rich diversification of two groups of secondary metabolities, the neolignans and benzylisoquinolines. From a survey of their distribution it becomes apparent that several shifts have led to the predominance of one of these two groups or their mutual exclusion in these families. Biogenetic considerations and correlation with morphological advancement suggest the evolutionary primacy of neolignans over benzylisoquinolines, but it is assumed that the capacity to produce both groups of substances must be very old. Apparently the presumed loss of benzylisoquinolines in various small families such as the Himantandraceae and Calycanthaceae has triggered the evolution of novel classes of compounds in compensation. Chemical changes leading to dissimilarities between sister groups as described in this paper may camouflage natural relationships.     

Protective effects of N-acetylserotonin against 6-hydroxydopamine-induced neurotoxicity

The present work studied in vivo neuroprotective effects of n-acetylserotonin (NAS), the immediate precursor of melatonin, on the dopaminergic system, in rats lesioned with the unilateral intrastriatal injection of the neurotoxin 6-hydroxydopamine (6-OHDA). Two weeks after the lesion, the dopamine receptor agonist, apomorphine, produced rotational asymmetry, and the NAS treatment significantly reduced the motor deficit following the apomorphine challenge. The apomorphine-induced rotational behavior was blocked by 84, 86 and 53% after NAS, at doses of 2, 5 and 10 mg/kg, i.p., respectively. The injection of 6-OHDA significantly decreased DA, DOPAC and HVA levels in the rat striatum. In contrast, the NAS (2, 5 and 10 mg/kg, i.p., daily for 7 days) treatment partially reversed the decreases caused by 6-OHDA, and the neurotransmitter levels were brought to approximately 50% of that observed in the contralateral sides. NAS was more efficient at the smaller doses. NAS (5 mg/kg) produced an up-regulation of D1 (37%) and D2 (37%) receptors associated with a decrease in Kd values.     

BCG modulation of anaphylactic antibody response, airway inflammation and lung hyperreactivity in genetically selected mouse strains (Selection IV-A)

The effect of Bacillus Calmette-Guérin (BCG) treatment in allergic pulmonary reaction was studied in mice genetically selected accordingly to a High (H-IVA) or Low (L-IVA) antibody responsiveness. Mice were immunized with ovalbumin (OVA) or OVA plus BCG. Two days after nasal antigenic challenge, seric IgE and IgG1 anti-OVA, eosinophils in pulmonary tissue, inflammatory cells in bronchoalveolar lavage and the compliance and conductance of respiratory system were evaluated. H-IVA mice were found more susceptible than L-IVA, and BCG was able to inhibit simultaneously the production of IgE, the bronchopulmonary inflammation and bronchial hyperresponsiveness in these genetically selected mice.     

Plasmodium falciparum: stage specific effects of a selective inhibitor of lactate dehydrogenase

Plasmodium falciparum lactate dehydrogenase (PfLDH) is essential for ATP generation. Based on structural differences within the active site between P. falciparum and human LDH, we have identified a series of heterocyclic azole-based inhibitors that selectively bind within the PfLDH but not the human LDH (hLDH) active site and showed anti-malarial activity in vitro and in vivo. Here we expand on an azole, OXD1, from this series and found that the anti-P. falciparum activity was retained against a panel of strains independently of their anti-malarial drug sensitivity profile. Trophozoites had relatively higher PfLDH enzyme activity and PfLDH-RNA expression levels than rings and were the most susceptible stages to OXD1 exposure. This is probably linked to their increased energy requirements and consistent with glycolysis being an essential metabolic pathway for parasite survival within the erythrocyte. Further structural elaboration of these azoles could lead to the identification of compounds that target P. falciparum through such a novel mechanism and with more potent anti-malarial activity.     

Spatial and temporal variations of hydrological conditions,nutrients and chlorophyll <Emphasis Type="Italic">a</Emphasis> in a Mediterranean coastal lagoon (Mar Menor,Spain)

The Mar Menor is a sheltered and hypersaline lagoon, with salinity ranges between 38 and 51 psu. The lagoon is threatened by several pressures and in the last decades detrimental impact on the natural community structure and dynamics have increased. In the watershed, agricultural practices are rapidly evolving from extensive dry crop farming to intensively irrigated crops, with increasing loads of nutrient and pollutants to the lagoon. Hydrological conditions, nutrients and chlorophyll a concentrations were analysed in 1997 and 2002–2003 in a grid of 20 stations in the lagoon. Different time scales, from daily to inter-annual, were considered. In the considered periods, the dissolved inorganic nitrogen (DIN) increased whilst phosphate decreased significantly. These contrasting patterns depended upon the increased agricultural loading for DIN and were due to the implementation of the wastewater works for phosphates. In 1997 and 2002, the highest nitrate concentrations were usually found on the west coast of the lagoon, close to the mouths of the main watercourses. In parallel, the lowest concentrations were detected at the inner coastline along “La Manga” sandy bar and “El Estacio” channel. Based on weekly data, correlations between chlorophyll a concentrations and environmental variables disagreed with traditional eutrophication models. Relationships between chlorophyll a and nutrients were negative, suggesting that in the short term phytoplankton controlled nutrient concentrations. Moreover, nitrate and phosphorous seemed to alternate as limiting factors. The relationships between chlorophyll a became positive when considering time lags and analysed at longer time scales (monthly or seasonal means), thus suggesting a very rapid response of primary producers to nutrient enrichment. A significant correlation between chlorophyll a concentration and fish larvae density was also found at all time scales analysed, suggesting a top-down control of the trophic web.     

Down under the southeastern Pacific: marine non-indigenous species in Chile

This article presents the first compilation of marine non-indigenous species (NIS) of algae and macro-invertebrates invading Chilean waters. A total of 32 cosmopolitan and non-cosmopolitan species are reported. Among them there are six species considered as extending their southern range of distribution in connection with El Niño events. The article highlights negative and positive impacts caused by marine NIS invasions. Among the first are Codium fragile var. tomentosoide, considered as a pest in Gracilaria chilensis aquaculture facilities in northern Chile, and Ciona intestinalis, a pest in scallop aquaculture installations. Among the second are bio-engineers species, such as the ascidian Pyura praeputialis and the sea grass Heterozostera tasmanica, which have caused an increase in local biodiversity and enhancement of nursery grounds via the creation of new habitats. Further more, invaders such as the algae Mastocarpus papillosus, Porphyra linearis and P. pseudolinearis represent new exploitable resources, extracted by coastal food gatherers along the coast (M. papillosus) or potential species to develop aquaculture. Additional information is presented on the anemone Anemonia alicemartinae, which appears to be a native species (?), having shown in the past 40–50 years, a geographical southward range extension of approximately 1900 km. The number of NIS reported for Chile is compared with those published for the southwestern Atlantic, South Africa, North America (Atlantic and Pacific coasts) and New Zealand. It is suggested that probably the low number of Chilean NIS is due to the fact that the Chilean coasts are environmentally less stressed than other coasts in the world, due to the scarcity of estuaries, gulfs, enclosed bays, lagoons and low human populations. These kinds of sheltered areas have been suggested as centers for bio-invasions, due to the high rate of human-mediated transfer and increase of pollutants. Furthermore, none of NIS reported from Chile show a fast geographical expansion rate (exception of A. alicemartinae), nor invading strategies such as those described for marine NIS in other latitudes, where notorious ecological unbalances following invasions have been observed. An alternative hypothesis is that the low number of marine NIS invading Chile is underestimated, since the modern list of species generated through specific taxonomically intensive port and harbor surveys is still lacking. Fifteen species (five invertebrate and 10 fish) have been deliberately imported to Chile for aquaculture. The invertebrates appear to be controlled within aquaculture facilities and have not established naturalized populations or caused direct ecological impacts on local communities. On the contrary, several millions of salmoniforms (and rainbow trout) have escaped from farming facilities in southern Chile and established naturalized populations. Studies on ecological impacts are lacking. These escapees are also playing a role in the enhancement of artisanal and sport fishery activities.     

Exploring the genome of Trypanosoma vivax through GSS and in silico comparative analysis

A survey of the Trypanosoma vivax genome was carried out by the genome sequence survey (GSS) approach resulting in 1,086 genomic sequences. A total of 455 high-quality GSS sequences were generated, consisting of 331 non-redundant sequences distributed in 264 singlets and 67 clusters in a total of 135.5 Kb of the T. vivax genome. The estimation of the overall G+C content, and the prediction of the presence of ORFs and putative genes were carried out using the Glimmer and Jemboss packages. Analysis of the obtained sequences was carried out by BLAST programs against 12 different databases and also using the Conserved Domain Database, InterProScan, and tRNAscan-SE. Along with the existing 23 T. vivax entries in the GenBank, the 32 putative genes predicted and the 331 non-redundant GSS sequences reported herein represent new potential markers for the development of PCRbased assays for specific diagnosis and typing of Trypanosoma vivax.     

7-Ketocholesterol-induced apoptosis. Involvement of several pro-apoptotic but also anti-apoptotic calcium-dependent transduction pathways

Oxysterols, and particularly 7-ketocholesterol, appear to be strongly involved in the physiopathology of atherosclerosis. These molecules are suspected to be cytotoxic to the cells of the vascular wall and monocytes/macrophages, particularly by inducing apoptosis. Previous studies have demonstrated that 7-ketocholesterol-induced apoptosis is triggered by a sustained increase of cytosolic-free Ca2+, which elicits the mitochondrial pathway of apoptosis by activation of the calcium-dependent phosphatase calcineurin, leading to dephosphorylation of the 'BH3 only' protein BAD. However, thorough study of the results suggests that other pathways are implicated in 7-ketocholesterol-induced cytotoxicity. In this study, we demonstrate the involvement of two other calcium-dependent pathways during 7-ketocholesterol-induced apoptosis. The activation of the MEK-->ERK pathway by the calcium-dependent tyrosine kinase PYK 2, a survival pathway which delays apoptosis as shown by the use of the MEK inhibitor U0126, and a pathway involving another pro-apoptotic BH3 only protein, Bim. Indeed, 7-ketocholesterol treatment of human monocytic THP-1 cells induces the release of Bim-LC8 from the microtubule-associated dynein motor complex, and its association with Bcl-2. Therefore, it appears that 7-ketocholesterol-induced apoptosis is a complex phenomenon resulting from calcium-dependent activation of several pro-apoptotic pathways and also one survival pathway.