Biological activities of the LXRα and β agonist, 4β-hydroxycholesterol,and of its isomer, 4α-hydroxycholesterol,on oligodendrocytes: Effects on cell growth and viability,oxidative and inflammatory status

The biochemical and biological properties of 4β-hydroxycholesterol and of its isomer, 4α-hydroxycholesterol, are not well known. So, we determined the ability of 4α- and 4β-hydroxycholesterol to react with LXRα and LXRβ, and we characterized the activities of these oxysterols on oligodendrocytes which are myelin synthesizing cells. The effects of 4α- and 4β-hydroxycholesterol were studied on 158N murine oligodendrocytes to assess their activities on cell growth and viability, oxidative and inflammatory status. To this end different parameters were used: cell counting with trypan blue; identification of dead cells and cell cycle analysis with propidium iodide; evaluation of mitochondrial depolarization, lysosomal membrane integrity, actin depolimerization, nuclear morphology, and superoxide anion production after staining with JC-1, acridine orange, rhodamine-phalloidin, Hoechst 33342, and dihydroethidium, respectively; evaluation of ultrastructural changes by transmission electron microscopy, and cytokine quantification with a cytometric bead array. Only 4β-hydroxycholesterol is a LXRα and β agonist. No cytotoxic effects were found with 4α-hydroxycholesterol except a slight inhibition of cell growth at elevated concentrations. At high concentrations, 4β-hydroxycholesterol was not only able to inhibit cell growth, but also to induce cell death associated with a loss of mitochondrial transmembrane potential, dysfunctions of lysosomal membrane integrity, and superoxide anion overproduction. These side effects were lower than those observed with 7-ketocholesterol and 25-hydroxycholesterol used as positive controls. On oligodendrocyte murine primary cultures, only lysosomal membrane integrity was slightly affected under treatment with 4α- and 4β-hydroxycholesterol. So, 4α- and 4β-hydroxycholesterol have different biological activities. Their ability to induce cytotoxic effects on oligodendrocytes can be considered as weak comparatively to 7-ketocholesterol and 25-hydroxycholesterol.     

Genetic structure and functioning of alien ship rat populations from a Corsican micro-insular complex

The detrimental effects of the introduced ship rat on bird species on the Lavezzi Mediterranean archipelago has led to the decision to eradicate the rodent from the main island, Lavezzu (73 ha), as well as from several neighbouring islets. A genetic study using eight microsatellite markers has revealed some of the dynamics of this rat population. First, it has been shown that the rat population was genetically stable (no departure from Hardy-Weinberg equilibrium and no linkage disequilibrium) and as suggested by paleontological data, established for a long time. This information is encouraging in term of viability of the eradication campaign in the long term, even if rare immigration events cannot be excluded. Second, this study shows that rats are likely to swim between the main island and the islets quite regularly since no clear genetic differentiation has been detected between them. This result is quite surprising since the ship rat is not known for its swimming abilities. Third, a cryptic genetic structure has been detected on the main island, with the north peninsula differentiated from the rest. This result correlates the observation of particular predation behaviours only observed in this part of the island. Finally, evolutionary hypotheses (e.g., dispersal limitation, emergence of family groups, local adaptation) are discussed to explain the genetic patterns observed and the population functioning inferred. These results should be of particular interest to wildlife managers concerned with rat eradications, and also provide clear insights into the study of other biological invasions.     

Interaction between AR signalling and CRKL bypasses casodex inhibition in prostate cancer

The underlying mechanism of failed androgen ablation therapy is unknown. It is recognised that under therapeutic conditions the androgen receptor (AR) remains functionally active independent of hormone stimulation and may function through an alternative pathway. We report a novel cooperative interaction between CRKL (an intracellular signalling adaptor protein) and the AR. We demonstrate by biochemical and genetic approaches that CRKL is associated with the AR complex and is localised in the nucleus of prostate cancer cells and patient tissue biopsies. The interaction between CRKL and the AR is functionally relevant as demonstrated by its presence on the enhancer region of an androgen regulated gene (human Kallikrein-2), its upregulation of PSA, and reduction in AR transactivation following its disruption by siRNA knockdown. In the presence of the AR inhibitor casodex, the expression of CRKL co-stimulated by growth factors is able to rescue AR activity independent of hormone. Our data provides insight on how a non-nuclear factor such as CRKL may interact with the AR complex to bypass hormone dependency by using an alternative growth factor signalling pathway in advanced prostate cancer.     

Rapid morphological changes,admixture and invasive success in populations of Ring-necked parakeets (<Emphasis Type="Italic">Psittacula krameri</Emphasis>) established in Europe

The Ring-necked parakeet (Psittacula krameri), native of Asia and Africa, is a very successful invasive species in Europe: it has been present there for over 50 years. A recent study showed that European invasive populations occupy a colder climatic niche than in their native range but the establishment of this tropical species in temperate regions remains unexplained. Two main hypotheses may explain the success of Ring-necked parakeet in Europe: admixture between individuals from different origins and/or rapid adaptation to new environmental conditions. In this study, we investigated with molecular data the origin of European populations of Ring-necked parakeets to assess whether these populations result from admixture between individuals from different source populations. We also investigated the morphology of individuals from European populations and from the native range to assess whether the invasive populations have morphologically diverged from their source and could have become adapted to European conditions. We found evidence of admixture in some of the European populations but not all of them. Admixture between individuals from different origins within European populations thus cannot explain alone their invasive success. Conversely, we found that the morphology of the individuals from European populations has diverged from the morphology of native individuals, in a similar direction. Rapid adaptation to European environmental conditions via phenotypic plasticity or natural selection could thus be a factor explaining the invasive success of Ring-necked parakeets in Europe.     

Synthesis of all-trans arachidonic acid and its effect on rabbit platelet aggregation

A simple and high-yielding method to convert natural all-cis PUFA derivatives to the corresponding all-trans geometrical isomers is described. The method is based on the thiyl radical-catalyzed cis-trans isomerization. The all-trans isomer of arachidonic acid was found to cause rabbit platelet aggregation at concentrations higher than 0.1 mM and inhibition of PAF-induced platelet aggregation in a concentration dependent manner with an IC(50) in the micromolar range.     

Deep-sea origin and in-situ diversification of chrysogorgiid octocorals

The diversity, ubiquity and prevalence in deep waters of the octocoral family Chrysogorgiidae Verrill, 1883 make it noteworthy as a model system to study radiation and diversification in the deep sea. Here we provide the first comprehensive phylogenetic analysis of the Chrysogorgiidae, and compare phylogeny and depth distribution. Phylogenetic relationships among 10 of 14 currently-described Chrysogorgiidae genera were inferred based on mitochondrial (mtMutS, cox1) and nuclear (18S) markers. Bathymetric distribution was estimated from multiple sources, including museum records, a literature review, and our own sampling records (985 stations, 2345 specimens). Genetic analyses suggest that the Chrysogorgiidae as currently described is a polyphyletic family. Shallow-water genera, and two of eight deep-water genera, appear more closely related to other octocoral families than to the remainder of the monophyletic, deep-water chrysogorgiid genera. Monophyletic chrysogorgiids are composed of strictly (Iridogorgia Verrill, 1883, Metallogorgia Versluys, 1902, Radicipes Stearns, 1883, Pseudochrysogorgia Pante & France, 2010) and predominantly (Chrysogorgia Duchassaing & Michelotti, 1864) deep-sea genera that diversified in situ. This group is sister to gold corals (Primnoidae Milne Edwards, 1857) and deep-sea bamboo corals (Keratoisidinae Gray, 1870), whose diversity also peaks in the deep sea. Nine species of Chrysogorgia that were described from depths shallower than 200 m, and mtMutS haplotypes sequenced from specimens sampled as shallow as 101 m, suggest a shallow-water emergence of some Chrysogorgia species.     

Is it worth eradicating the invasive pest Rattus norvegicus from Molène archipelago? Genetic structure as a decision-making tool

Genetic variability and structure were estimated by microsatellite analysis at 7 loci in brown rat populations (Rattus norvegicus) from the Iroise insular complex and neighbouring mainland (Brittany, France). Island genetic diversity is lower than on the mainland and a highly significant positive correlation was found between mean heterozygosity and the logarithm of island area, which is consistent with theoretical expectations. Rattus norvegicus populations are substructured at a kilometric scale, both on the islands and on the mainland. Intra-island structuration is extremely high, suggesting that no effective migration occurs between islands or with the mainland. Historical and genetical evidence suggest that R. norvegicus was introduced independently on Ouessant and Molène archipelago, with a low and a high founder effect respectively. These results are discussed in terms of recolonization probability of islands that have been cleared of R. norvegicus, which illustrates the usefulness of genetic markers in determining parameters of interest to the conservation biologist.     

Additional rDNA ITS sequences and its phylogenetic consequences for the genus Leveillula with emphasis on conidium morphology

Taxonomy of the genus Leveillula has long been considered as a challenge in powdery mildew systematics. The rDNA diversity has recently been used for phylogenetic analysis of several specimens of the genus Leveillula. In the present study, additional rDNA ITS sequences are provided and a new phylogenetic analysis is carried out aiming at a better understanding of the genetic diversity in the genus Leveillula. New analyses confirmed that L. taurica is unique in the genus, as it exhibits an intraspecific gene sequence diversity considerably higher than in other species. In several cases L. taurica s. lat. on a certain host plant species has a sequence different from L. taurica on other host plants. Moreover, DNA data indicated different lineages among L. taurica specimens which were hardly distinguishable by morphology. More than one genotype occurring on a single host is sometimes possible. According to these results, several races such as Leveillula on Artemisia, Acroptilon, Onobrychis, are molecularly well characterized. While there is enough molecular evidence to delimit such races as independent taxa, clear morphological delimitations between these new and already published taxa are very difficult or even impossible. However, ecological features, and above all, host specificity for biotrophic fungi such as powdery mildew, would be a good criterion to discriminate cryptic taxa along with rDNA sequences. In fact, many collections of Leveillula strains on different hosts show their own type of conidial morphology, which is usually consistent for a strain on a single host species. Hence, we have proposed to describe new species for Leveillula on some host plants such as Artemisia, Acroptilon, Echinops and Onobrychis.