The role of fibroblast growth factors in vascular development

Fibroblast growth factors (FGFs) are considered angiogenic factors, yet the exact relationship between FGF and vascular development in normal and pathological tissue has long remained elusive. However, recent results from gene inactivation and transgenic studies in mice and in culture systems have demonstrated the role of FGFs in vessel assembly and sprouting. FGFs also promote blood-vessel branching and induce lymphangiogenesis. Novel players in FGF-mediated angiogenesis have been identified, such as p38 mitogen-activated protein kinase. Tumour angiogenesis is regulated by FGFs directly or indirectly via secondary angiogenesis factors, such as vascular endothelial growth factor. The newly established angiogenic role of FGFs makes FGF or molecules targeting FGF and its receptor promising candidates for the development of novel therapeutics.     

A novel specific edge effect correction method for RNA interference screenings

MOTIVATION: High-throughput screening (HTS) is an important method in drug discovery in which the activities of a large number of candidate chemicals or genetic materials are rapidly evaluated. Data are usually obtained by measurements on samples in microwell plates and are often subjected to artefacts that can bias the result selection. We report here a novel edge effect correction algorithm suitable for RNA interference (RNAi) screening, because its normalization does not rely on the entire dataset and takes into account the specificities of such a screening process. The proposed method is able to estimate the edge effects for each assay plate individually using the data from a single control column based on diffusion model, and thus targeting a specific but recurrent well-known HTS artefact. This method was first developed and validated using control plates and was then applied to the correction of experimental data generated during a genome-wide siRNA screen aimed at studying HIV-host interactions. The proposed algorithm was able to correct the edge effect biasing the control data and thus improve assay quality and, consequently, the hit-selection step.     

An Image-Based Drug Susceptibility Assay Targeting the Placental Sequestration of Plasmodium falciparum-Infected Erythrocytes

Placental malaria is a significant cause of all malaria-related deaths globally for which no drugs have been developed to specifically disrupt its pathogenesis. To facilitate the discovery of antimalarial drugs targeting the cytoadherence process of Plasmodium-infected erythrocytes in the placenta microvasculature, we have developed an automated image-based assay for high-throughput screening for potent cytoadherence inhibitors in vitro. Parasitized erythrocytes were drug-treated for 24 h and then allowed to adhere on a monolayer of placental BeWo cells prior to red blood cell staining with glycophorin A antibodies. Upon image-acquisition, drug effects were quantified as the proportion of treated parasitized erythrocytes to BeWo cells compared to the binding of untreated iRBCs. We confirmed the reliability of this new assay by comparing the binding ratios of CSA- and CD36-panned parasites on the placental BeWo cells, and by quantifying the effects of chondroitin sulfate A, brefeldin A, and artemisinin on the binding. By simultaneously examining the drug effects on parasite viability, we could discriminate between cytoadherence-specific inhibitors and other schizonticidal compounds. Taken together, our data establish that the developed assay is highly suitable for drug studies targeting placental malaria, and will facilitate the discovery and rapid development of new therapies against malaria.     

Les photorécepteurs des Collemboles, étude ultrastructurale

Résumé L'étude ultrastructurale de l'appareil dioptrique des photorécepteurs des Collemboles adultes a permis de reconsidérer la structure des formations oculaires à ommatidies aggrégées. Quatre types de cornéules ont été reconnus, dont les plus remarquables sont ceux à mamelons cornéens. Les cellules cristalliniennes au nombre de quatre assurent alternativement une double fonction au cours de chaque cycle de la mue. Sur les faces distales, les cellules élaborent le matériel cuticulaire de la cornéule; vers l'intérieur elles sécrètent le cristallin. Les cellules de Semper réalisent ainsi une fonction cornéagène et une fonction cristallogène. La répartition spatiale des organites intracellulaires en couches concentriques est une caractéristique des Collemboles. Chaque cellule cristallinienne envoie vers la membrane basale un processus tubulaire contenant des granules denses de nombreux microtubules et du glycogène en faible quantité. Les cônes cristallins présentent une grande diversité de forme de structure et de composition chimique. Suivant les groupes le cristallin peut être une formation intracellulaire ou extracellulaire, simple ou quadripartite. La présence de petits cristallins satellites associés à un cristallin unique reste inexpliquée mais caractérise une espèce troglobie Tomocerus problematicus. Deux cellules dites cornéagènes à cytoplasme toujours pauvre en organites intracytoplasmiques, avec ou sans pigment, complètent l'appareil dioptrique des ommas des Collemboles.

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Photoreceptors of Collembola, an ultrastructural studyI. The Dioptric Apparatus

Summary Ultrastructural features of the dioptric apparatus of photoreceptors of adult Collembola described by the author has enabled the author to compare the structure of ocular formations with aggregated ommatidia. Four different types of corneulae have been determined, the most remarkable of which are those showing corneal nipples. The four crystalline cells have alternately different functions during each molting cycle. On their distal surfaces, the cells elaborate cuticular material of the corneula; proximally, they secrete a crystalline cone. The Semper cells thus have both corneogenous and crystallogenous functions. The typically concentric spatial distribution of intracellular organelles in these cells is a characteristic feature for Collembola. Each crystalline cell sends towards the basal membrane a tubular process containing granules, numerous microtubules, and a small amount of glycogen. The shape, the structure, and the chemical composition of the crystalline cones are highly variable. In Collembola, the crystalline formation can either be intracellular or extracellular, and it can be simple or quadripartite. No explanation has yet been advanced for the existence of small crystalline satellites which appear to be associated with the single large crystalline cones; this association is characteristic for the troglobian species Tomocerus problematicus. The dioptric apparatus of Collembolan ommatidia is completed by the presence of two corneogenous cells, the cytoplasm of which contains few organelles and in some cases pigments.

     

Association of hydrophobically-modified poly(ethylene glycol) with fusogenic liposomes

We present results on using cooperative interactions to shield liposomes by incorporating multiple hydrophobic anchoring sites on polyethylene glycol (PEG) polymers. The hydrophobically-modified PEGs (HMPEGs) are comb-graft polymers with strictly alternating monodisperse PEG blocks (M_w=6, 12, or 35 kDa) bonded to C18 stearylamide hydrophobes. Cooperativity is varied by changing the degree of oligomerization at a constant ratio of PEG to stearylamide. Fusogenic liposomes prepared from N-C12-DOPE:DOPC 7:3 (mol:mol) were equilibrated with HMPEGs. Affinity for polymer association to liposomes increases with the degree of oligomerization; equilibrium constants (given as surface coverage per equilibrium concentration of free polymer) for 6 kDa PEG increased from 6.1±0.8 (mg/m²)/(mg/ml) for 2.5 loops to 78.1±12.2 (mg/m²)/(mg/ml) for 13 loops. In contrast, the equilibrium constant for distearoylphosphatidylethanolamine-poly(ethylene glycol) (DSPE-PEG5k) was 0.4±0.1 (mg/m²)/(mg/ml).The multi-loop HMPEGs demonstrate higher levels of protection from complement binding than DSPE-PEG5k. Greater protection does not correlate with binding strength alone. The best shielding was by HMPEG6k-DP3 (with three 6 kDa PEG loops), suggesting that PEG chains with adequate surface mobility provide optimal protection from complement opsonization. Complement binding at 30 min and 12 h demonstrates that protection by multi-looped PEGs is constant whereas DSPE-PEG5k initially protects but presumably partitions off of the surface at longer times.     

Nitrile glucosides and serotobenine from Campylospermum glaucum and Ouratea turnarea

Two nitrile glucosides (1S,3S,4S,5R)-4-benzoyloxy-2-cyanomethylene-3,5-dihydroxycyclohexyl-1-O-beta-glucopyranoside (campyloside A) and (1S,3S,4S,5R)-5-benzoyloxy-2-cyanomethylene-3-hydroxy-4-(2-pyrrolcarboxyloxy)cyclohexyl-1-O-beta-glucopyranoside (campyloside B) were isolated from the stem roots of Campylospermum glaucum, whereas serotobenine was isolated from Ouratea turnarea. The structure elucidations were based on spectroscopic evidence. The biological assays of compounds and crude extract of plant species showed good antimicrobial activity of crude extracts against Gram-positive cocci.     

Regulation of vascular development by fibroblast growth factors

Fibroblast growth factors (FGFs) are potent stimulators of angiogenesis in vitro and in vivo. However, the precise role of FGFs and vascular development in normal and pathological tissue has long remained ill defined. Recently, substantial progress has been made toward a better understanding of their role. Genetic studies in mice or in culture systems indicate a role for FGFs in vessel assembly and sprouting. FGFs also stimulate blood vessel branching and lymphangiogenesis. The molecular mechanisms by which FGFs mediate angiogenesis are also better understood. Finally, the FGF/FGF-receptor system has become a focus for the development of novel therapeutic strategies for the treatment of angiogenesis-related diseases such as tissue ischemia.Work described herein from our laboratory was supported by grants from the Ligue Nationale contre le Cancer, the Association de la Recherche sur le Cancer, Rétina France, the Institut National de la Santé et de la Recherche Médicale (INSERM), and the Ministère de la Recherche     

Food sharing and affiliation: An experimental and longitudinal study in cockatiels (Nymphicus hollandicus)

Food sharing has attracted much attention because of its apparently altruistic nature and its link to prosociality. However, food sharing has been mostly studied in a reproductive context, during courtship and parental care, where the fitness benefits are obvious. We still lack a clear understanding of the functions of food sharing outside any reproductive context and within social groups of same‐aged peers. Previous studies suggest that cofeeding, the action to let another animal feed from the same monopolizable food source, may be used to build and strengthen bonds between individuals. This may be particularly crucial in social birds forming long‐term associations between mates or siblings such as psittacids and corvids. Here, we investigated food sharing and affiliative behaviors such as allopreening in a psittacine species, namely in a group of captive juvenile cockatiels (Nymphicus hollandicus) consisting of five siblings and five unrelated birds. Our main objective was to study the developmental pattern of food sharing over time and its implication in social bonding depending on kinship, affiliation, and sex. Studying cockatiels in this context is providing many new information since most of the studies on food sharing in birds focused on corvids. We found that, contrary to jackdaws, cockatiels continued to share food with multiple individuals, although the frequency of cofeeding as well as the number of cofeeding partners decreased over time. Cockatiels shared more food with their siblings than with other conspecifics but they were not more likely to do cofeeding with birds of the opposite sex. We also found evidence that young cockatiels exchanged more food with those from whom they received food (reciprocity) and, to a lesser extent, allopreening (interchange), than from other cockatiels. Our findings suggest that in cockatiels, food sharing within social groups serves the formation (and maintenance) of affiliative bonds, especially between siblings, rather than pair bonds, but might additionally be explained by reciprocity, interchange, and harassment avoidance.     

La séquence de Moulin Quignon est-elle une séquence archéologique ?

The sequence of the Moulin Quignon quarry yielded archaeological findings (faunal remains, artefacts) and some of them are well located in the stratigraphy thanks to Jacques Boucher de Perthes and colleagues. These remains are often used to attest the early age of the site and the human remains. Some bifaces have been found in close relationship to the human remains and, in particular, the mandible found in 1863. Thanks to the handwritten label put on the pieces and their deposit at the National Museum of Natural History (Paris), it is possible to study them again in relation with the sequence. The study concerns the rare faunal remains and the bifaces given, among others, by Boucher de Perthes to the Museum. The paleontological and technological analyses allow us replacing the lithic material among the north-western European data. The material is presented according to the historical context of his discovery.