Initiation of phospholipomannan ß-1,2 mannosylation involves Bmts with redundant activity, influences its cell wall location and regulates ß-glucans homeostasis but is dispensable for Candida albicans systemic infection.

Pathogenic and non-pathogenic fungi synthesize glycosphingolipids, which have a crucial role in growth and viability. Glycosphingolipids also contribute to fungal-associated pathogenesis. The opportunistic yeast pathogen Candida albicans synthesizes phospholipomannan (PLM), which is a glycosphingolipid of the mannosylinositol phosphorylceramide family. Through its lipid and glycan moieties, PLM contributes to the initial recognition of the yeast, causing immune system disorder and persistent fungal disease through activation of host signaling pathways. The lipid moiety of PLM activates the deregulation signaling pathway involved in yeast phagocytosis whereas its glycan moiety, composed of ß-1,2 mannosides (ß-Mans), participates to inflammatory processes through a mechanism involving Galectin-3. Biosynthesis of PLM ß-Mans involves two ß-1,2 mannosyltransferases (Bmts) that initiate (Bmt5) and elongate (Bmt6) the glycan chains. After generation of double bmtsΔ mutants, we show that Bmt5 has redundant activity with Bmt2, which can replace Bmt5 in bmt5Δ mutant. We also report that PLM is located in the inner layer of the yeast cell wall. PLM seems to be not essential for systemic infection of the yeast. However, defect of PLM ß-mannosylation increases resistance of C. albicans to inhibitors of ß-glucans and chitin synthesis, highlighting a role of PLM in cell wall homeostasis.

Higher sensitivity of Adamts12-deficient mice to tumor growth and angiogenesis.

ADAMTS (a disintegrin and metalloproteinase domain with thrombospondin motifs) constitute a family of endopeptidases related to matrix metalloproteinases. These proteases have been largely implicated in tissue remodeling and angiogenesis associated with physiological and pathological processes. To elucidate the in vivo functions of ADAMTS-12, we have generated a knockout mouse strain (Adamts12(-/-)) in which Adamts12 gene was deleted. The mutant mice had normal gestations and no apparent defects in growth, life span and fertility. By applying three different in vivo models of angiogenesis (malignant keratinocyte transplantation, Matrigel plug and aortic ring assays) to Adamts12(-/-) mice, we provide evidence for a protective effect of this host enzyme toward angiogenesis and cancer progression. In the absence of Adamts-12, both the angiogenic response and tumor invasion into host tissue were increased. Complementing results were obtained by using medium conditioned by cells overexpressing human ADAMTS-12, which inhibited vessel outgrowth in the aortic ring assay. This angioinhibitory effect of ADAMTS-12 was independent of its enzymatic activity as a mutated inactive form of the enzyme was similarly efficient in inhibiting endothelial cell sprouting in the aortic ring assay than the wild-type form. Altogether, our results show that ADAMTS-12 displays antiangiogenic properties and protect the host toward tumor progression.

Reduction of brain metastases in plasminogen activator inhibitor-1-deficient mice with transgenic ocular tumors.

Plasminogen activator inhibitor-1 is known to play a paradoxical positive role in tumor angiogenesis, but its contribution to metastatic spread remains unclear. We studied the impact of plasminogen activator inhibitor (PAI)-1 deficiency in a transgenic mouse model of ocular tumors originating from retinal epithelial cells and leading to brain metastasis (TRP-1/SV40 Tag mice). PAI-1 deficiency did not affect primary tumor growth or vascularization, but was associated with a smaller number of brain metastases. Brain metastases were found to be differentially distributed between the two genotypes. PAI-1-deficient mice displayed mostly secondary foci expanding from local optic nerve infiltration, whereas wild-type animals displayed more disseminated nodules in the scissura and meningeal spaces. SuperArray GEarray analyses aimed at detecting molecules potentially compensating for PAI-1 deficiency demonstrated an increase in fibroblast growth factor-1 (FGF-1) gene expression in primary tumors, which was confirmed by reverse transcription-polymerase chain reaction and western blotting. Our data provide the first evidence of a key role for PAI-1 in a spontaneous model of metastasis and suggest that angiogenic factors, such as FGF-1, may be important for primary tumor growth and may compensate for the absence of PAI-1. They identify PAI-1 and FGF-1 as important targets for combined antitumor strategies.

Single-crystal study of the m = 2 tubular cobalt oxide, Bi(4)Sr(12)Co(8)O(30-delta).

The structure of the m = 2 tubular compound Bi(4)Sr(12)Co(8)O(30-delta), bismuth strontium cobalt oxide, was determined by single-crystal X-ray diffraction. This phase of orthorhombic symmetry exhibits a very strong tetragonal pseudosymmetry. The structure consists of 90 degrees -oriented Bi(2)Sr(2)CoO(6+delta) slices, four Co atoms wide, forming [Sr(4)Co(4)O(13)](infinity) pillars at their intersection. The Co atoms in these pillars form four corner-sharing CoO(5) bipyramids. In the resulting [Co(4)O(13)] cluster, an anionic disorder is evidenced and discussed. Then, an accurate description of the particular structure of the pillars is given. Finally, a comparison with the Mn tubular compound Bi(3.6)Sr(12.4)Mn(8)O(30-delta) is carried out.

Status of Plasmodium falciparum towards catalase.

The role of endogenous and internalized catalase in the protection of Plasmodium against oxidant stress was studied. Catalase activities were measured in isolated Plasmodium falciparum at different stages of intererythrocytic development. Activities measured at late schizont stages were compared to parasite markers (glutamate dehydrogenase, SOD) and to red blood cell markers (haemoglobin, Cu/Zn-SOD). The fate of the host cell catalase in the parasite digestive system was studied by immunoelectron microscopy using monoclonal antibodies. The internalized catalase appeared to be dissociated in the digestive system of the parasite and inactivated. To examine the protective role of the endogenous and internalized catalase in the parasite protection against oxidant stress, parasites were cultivated at two oxygen concentrations (5% and 20%) in inhibited catalase red blood cells. These experiments suggested that the catalases present both in red blood cell and parasite are not essential when parasites are cultivated under 5% oxygen, but are necessary to protect the parasite under 20% oxygen. Catalase may not be the main protective enzyme involved in the protection of P. falciparum in standard in vitro culture conditions, but may become critical under the higher oxygen tensions conditions encountered in vivo.

[A case of abdominal aortic coarctation]. / A propos d'un cas de coarctation de l'aorte abdominale.

Report of a case with segmental thrombosis of the infrarenal abdominal aorta in a young person secondary to coarctation (probably congenital). Review of the literature.

Resolution of Penicillium roqueforti toxin and eremofortins A, B, and C by high-performance liquid chromatography.

A method for the quantitative analysis of Penicillium roqueforti toxin using a high-performance liquid chromatography system is proposed.