Vascular development: from precursor cells to branched arterial and venous networks

The adult vascular system is composed of an arterial, a venous and a lymphatic compartment. These different compartments respectively provide oxygen and nutrients to peripheral organs, remove carbon dioxide and waste products and maintain an immune barrier to defend the host against foreign organisms. Malfunctions of the vascular system represent a major cause of mortality and disease in developed countries. Understanding of the molecular mechanisms regulating vascular system development and maintenance is thus crucial for the design of therapies to cure vascular diseases. The molecules implicated in the control of physiological and pathological angiogenesis in the adult already function during embryonic development. Indeed, the survival of the embryo also critically depends on the establishment of a functional circulatory loop. Here we review our current knowledge about the emergence of endothelial precursor cells in the embryo, of their assembly into the primary vascular plexus and of the remodeling of this plexus into arteries and veins. We also focus on the molecular mechanisms controlling the development of arteries, veins and lymphatic vessels.     

Genetic polymorphism of the human cytochrome CYP2A13 in a French population: implication in lung cancer susceptibility

The human cytochrome CYP2A13, which is mainly expressed in the respiratory tract, has been shown to be highly efficient in vitro in the metabolism of tobacco-smoke carcinogens and procarcinogens such as 4-methylnitroso-1-(3-pyridyl)-1-butanone (NNK). In order to investigate the extent of CYP2A13 genetic polymorphism in a French Caucasian population of 102 individuals, a screening for sequence variations in the 5'-untranslated and protein encoding regions of its gene was performed using a polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) strategy. Six polymorphisms in the coding region were identified, including two rare missense mutations (C474G or Asp158Glu, G967T or Val323Leu) and one nonsense mutation (Arg101Stop). This deleterious mutation, the most frequent (5%) in our population, presumably encodes a severely truncated protein. The influence of the nonsense mutation in lung cancer susceptibility was examined by PCR-SSCP using peripheral blood DNA from 204 cases of lung cancer and 201 controls. The CYP2A13*7 allele, which harbours the C301T mutation, was present in 2.0% of controls and 3.4% of cases. However, multivariate analysis showed an elevated risk for small cell lung cancer in subjects heterozygous for the null allele (odds ratio OR=9.9; 95% confidence interval CI=1.9-52.2). This increased risk was not linked to other histological types of lung cancer.     

VEGF neutralizing aerosol therapy in primary pulmonary adenocarcinoma with K-ras activating-mutations

K-ras mutations promote angiogenesis in lung cancer and contribute to the drug resistance of cancer cells. It is not clear whether K-ras mutated adenocarcinomas are sensitive to anti-angiogenic therapy with monoclonal antibodies (mAbs) that target vascular endothelial growth factor (VEGF). Anti-angiogenic mAbs are usually delivered systemically, but only a small proportion reaches the lung after intravenous injection. We investigated the relevance of a non-invasive pulmonary route for the delivery of anti-VEGF mAbs in the mouse K-ras^LA1 model. We found that pulmonary delivery of these mAbs significantly reduced the number of tumor lesions and inhibited malignant progression. The antitumor effect involves the VEGFR2-dependent inhibition of blood vessel growth, which impairs tumor proliferation. Pharmacokinetic analysis of aerosolized anti-VEGF showed its low rate of passage into the bloodstream, suggesting that this delivery route is associated with reduced systemic side effects. Our findings highlight the value of the aerosol route for administration of anti-angiogenic mAbs in pulmonary adenocarcinoma with K-ras activating-mutations.     

Antimicrobial Histones and DNA Traps in Invertebrate Immunity: EVIDENCES IN CRASSOSTREA GIGAS*

Although antimicrobial histones have been isolated from multiple metazoan species, their role in host defense has long remained unanswered. We found here that the hemocytes of the oyster Crassostrea gigas release antimicrobial H1-like and H5-like histones in response to tissue damage and infection. These antimicrobial histones were shown to be associated with extracellular DNA networks released by hemocytes, the circulating immune cells of invertebrates, in response to immune challenge. The hemocyte-released DNA was found to surround and entangle vibrios. This defense mechanism is reminiscent of the neutrophil extracellular traps (ETs) recently described in vertebrates. Importantly, oyster ETs were evidenced in vivo in hemocyte-infiltrated interstitial tissues surrounding wounds, whereas they were absent from tissues of unchallenged oysters. Consistently, antimicrobial histones were found to accumulate in oyster tissues following injury or infection with vibrios. Finally, oyster ET formation was highly dependent on the production of reactive oxygen species by hemocytes. This shows that ET formation relies on common cellular and molecular mechanisms from vertebrates to invertebrates. Altogether, our data reveal that ET formation is a defense mechanism triggered by infection and tissue damage, which is shared by relatively distant species suggesting either evolutionary conservation or convergent evolution within Bilateria.     

Kallymenia crouaniorum (Kallymeniaceae,Rhodophyta), a new red algal species from the Laminaria hyperborea understorey community

In this paper we describe Kallymenia crouaniorum Vergés & Le Gall, sp. nov. (Kallymeniaceae), a new marine red alga from the north-eastern Atlantic Ocean. rbcL and LSU sequences of this species, previously misidentified in the field as Kallymenia reniformis, diverged from those of other Kallymenia species by at least 7.5% and 5.2%, respectively. Kallymenia crouaniorum also has a set of distinctive vegetative and reproductive characteristics, including a deeply lacerate frond, a short stipe, dentate margins, large cortical cells up to 110 μm in diameter, highly refractive stellate medullary cells with arms up to 1000 μm in length, and a monocarpogonial branch system. Molecular phylogenies inferred from rbcL and LSU data indicated, albeit with weak support, that this new species is a sister taxon of a lineage encompassing the generitype K. reniformis, as well as most species of Kallymenia included in the phylogenetic analysis. The main morphological characters that delineate monocarpogonial Kallymenia species are presented. Moreover, after reviewing the literature and several herbarium specimens, we found in the Weber-van Bosse Herbarium a specimen collected at Roscoff in August 1894 with the anatomical characters of the species described here, confirming that this newly described species has in fact been overlooked and is not a recent introduction.     

Complementarity of Rotating Video and Underwater Visual Census for Assessing Species Richness,Frequency and Density of Reef Fish on Coral Reef Slopes

Estimating diversity and abundance of fish species is fundamental for understanding community structure and dynamics of coral reefs. When designing a sampling protocol, one crucial step is the choice of the most suitable sampling technique which is a compromise between the questions addressed, the available means and the precision required. The objective of this study is to compare the ability to sample reef fish communities at the same locations using two techniques based on the same stationary point count method: one using Underwater Visual Census (UVC) and the other rotating video (STAVIRO). UVC and STAVIRO observations were carried out on the exact same 26 points on the reef slope of an intermediate reef and the associated inner barrier reefs. STAVIRO systems were always deployed 30 min to 1 hour after UVC and set exactly at the same place. Our study shows that; (i) fish community observations by UVC and STAVIRO differed significantly; (ii) species richness and density of large species were not significantly different between techniques; (iii) species richness and density of small species were higher for UVC; (iv) density of fished species was higher for STAVIRO and (v) only UVC detected significant differences in fish assemblage structure across reef type at the spatial scale studied. We recommend that the two techniques should be used in a complementary way to survey a large area within a short period of time. UVC may census reef fish within complex habitats or in very shallow areas such as reef flat whereas STAVIRO would enable carrying out a large number of stations focused on large and diver-averse species, particularly in the areas not covered by UVC due to time and depth constraints. This methodology would considerably increase the spatial coverage and replication level of fish monitoring surveys.     

Molecular Characterization of Clostridium tetani Strains by Pulsed-Field Gel Electrophoresis and Colony PCR

Pulsed-field gel electrophoresis and PCR were applied for the first time to the molecular characterization of Clostridium tetani. Among five strains tested, one (CN1339) turned out to contain a mixture of two genetically different clones and two (D11 and G761) to contain bacteria differing by the presence or absence of the 74-kb plasmid harboring the tetX gene.     

Break zones in the distributions of alleles and species in alpine plants

Aim We test for the congruence between allele‐based range boundaries (break zones) in silicicolous alpine plants and species‐based break zones in the silicicolous flora of the European Alps. We also ask whether such break zones coincide with areas of large elevational variation. Location The European Alps. Methods On a regular grid laid across the entire Alps, we determined areas of allele‐ and species‐based break zones using respective clustering algorithms, identifying discontinuities in cluster distributions (breaks), and quantifying integrated break densities (break zones). Discontinuities were identified based on the intra‐specific genetic variation of 12 species and on the floristic distribution data from 239 species, respectively. Coincidence between the two types of break zones was tested using Spearman’s correlation. Break zone densities were also regressed on topographical complexity to test for the effect of elevational variation. Results We found that two main break zones in the distribution of alleles and species were significantly correlated. Furthermore, we show that these break zones are in topographically complex regions, characterized by massive elevational ranges owing to high mountains and deep glacial valleys. We detected a third break zone in the distribution of species in the eastern Alps, which is not correlated with topographic complexity, and which is also not evident from allelic distribution patterns. Species with the potential for long‐distance dispersal tended to show larger distribution ranges than short‐distance dispersers. Main conclusions We suggest that the history of Pleistocene glaciations is the main driver of the congruence between allele‐based and species‐based distribution patterns, because occurrences of both species and alleles were subject to the same processes (such as extinction, migration and drift) that shaped the distributions of species and genetic lineages. Large elevational ranges have had a profound effect as a dispersal barrier for alleles during post‐glacial immigration. Because plant species, unlike alleles, cannot spread via pollen but only via seed, and thus disperse less effectively, we conclude that species break zones are maintained over longer time spans and reflect more ancient patterns than allele break zones.