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Indoor aquatic mesocosms were designed to mimic pond ecosystems contaminated by a continuous point-source discharge of cerium oxide nanoparticles (CeO2-NPs). Bare and citrate-coated CeO2-NPs exhibited different chemical and colloidal behaviors in the aquatic mesocosms. Bare CeO2-NPs were chemically stable but quickly homo-aggregated and settled out of the water column. Citrate-coated NPs both homo- and hetero-aggregated but only after the several days required to degrade the citrate coating. While they were more stable as a colloidal suspension, coated CeO2-NPs dissolved faster due to surface complexation with citrate, which resulted in the release of dissolved Ce into the water column. The different distributions over time between water/sediment or dissolved/particulate forms of Ce controlled the availability of Ce to benthic grazers (mollusk Planorbarius corneus) and planktonic filter feeders (copepod Eudiaptomus vulgaris).

We report on the synthesis of a series of lipopolyamine telomers, [I(Asp)-14,nA(NH), I(His)-18,nA(NH), I-18,nB(NMe), Gal-nA(NH)], and random cotelomers, [I-18,nA(NH)-nB(NMe) and I-18,nA(NH)-nC(OH)], and on their in vitro gene transfer capability. They were obtained by a telomerization process of various amino-acrylamide taxogens with various lipophilic thiol telogens which might also contain an aspartic or a histidine residue or with a thiogalactosyle derivative. For N/P ratios (N = number of (co)telomer amine equivalents, P = number of DNA phosphates) from 0.8 to 10, these polyamine (co)telomers condensed DNA, with or without the use of DOPE, forming (co)teloplexes of mean sizes less than 200 nm, except for N/P 1.25 for which precipitates were observed. Some trends, structure−transfection efficiency relationships, were established. Thus, aspartic-containing telomers were found to lead to efficient formulations for plasmid delivery to A549 cells and for N/P ratios from 1.25 to 5.

There is a need for the development of nonviral gene transfer systems with improved and original properties. “Fluorinated” lipoplexes are such candidates, as supported by the remarkably higher in vitro and in vivo transfection potency found for such fluorinated lipoplexes as compared with conventional ones or even with PEI-based polyplexes (Boussif, O., Gaucheron, J., Boulanger, C., Santaella, C., Kolbe, H. V. J., Vierling, P. (2001) Enhanced in vitro and in vivo cationic lipid-mediated gene delivery with a fluorinated glycerophosphoethanolamine helper lipid. J. Gene Med. 3, 109−114). Here, we describe the synthesis of fluorinated glycerophosphoethanolamines (F-PEs), close analogues of dioleoylphosphatidylethanolamine (DOPE), and report on their lipid helper properties vs that of DOPE, as in vitro gene transfer components of fluorinated lipoplexes based on pcTG90, DOGS (Transfectam), or DOTAP. To evaluate the contribution of the F-PEs to in vitro lipoplex-mediated gene transfer, we examined the effect of including the F-PEs in lipoplexes formulated with these cationic lipids (CL) for various CL:DOPE:F-PE molar ratios [1:(1 − x):x with x = 0, 0.5 and 1; 1:(2 − y):y with y = 0, 1, 1.5, and 2], and various N/P ratios (from 10 to 0.8, N = number of CL amines, P = number of DNA phosphates). Irrespective of the F-PE chemical structure, of the colipid F-PE:DOPE composition, and of the N/P ratio, comparable transfection levels to those of their respective control DOPE lipoplexes were most frequently obtained when using one of the F-PEs as colipid of DOGS, pcTG90, or DOTAP in place of part of or of all DOPE. However, a large proportion of DOGS-based lipoplexes were found to display a higher transfection efficiency when formulated with the F-PEs rather than with DOPE alone while the opposite tendency was evidenced for the DOTAP-based lipoplexes. The present work indicates that “fluorinated” lipoplexes formulated with fluorinated helper lipids and conventional cationic lipids are very attractive candidates for gene delivery. It confirms further that lipophobicity and restricted miscibility of the lipoplex lipids with the endogenous lipids does not preclude efficient gene transfer and expression. Their transfection potency is rather attributable to their unique lipophobic and hydrophobic character (resulting from the formulation of DNA with fluorinated lipids), thus preventing to some extent DNA from interactions with lipophilic and hydrophilic biocompounds, and from degradation.

We describe the synthesis of a α-galacto-ω-spermine bolaamphiphile (GalSper) and report on the gene transfer mediated with lipoplexes it forms either when used alone or in conjunction with DOPE or with DOGS (Transfectam). Lipofection with GalSper was investigated with human HepG2 or murine BNL-CL2 hepatocytes expressing the asialo-glycoprotein (ASGP) receptor, which displays a high affinity for galactosyl residues, or with A549 cells which do not express ASGP. Although lower luciferase expression levels in BNL-CL2 and in HepG2 cells were obtained with GalSper/DOPE N/P 2.5 lipoplexes as compared with control DOGS/DOPE N/P 2.5 particles or with the more positively charged N/P 5 particles (yet through a different mechanism), specific receptor-mediated endocytosis of DNA can be achieved with this targeted cationic GalSper bolaamphiphile presenting a single galactose residue. The present work suggests that GalSper-based DNA formulations appear as promising synthetic vectors for specific gene delivery to ASGP(+) cells.

Fluorinated double-chain lipospermines (one or both of these chains being ended by a highly fluorinated tail of various length) which are close analogues of DOGS (Transfectam) were designed as synthetic vectors for gene delivery. For N/P ratios (N = number of amine functions of the lipid; P = number of DNA phosphates) from 0.8 to 10, these lipospermines condensed DNA, with or without the use of DOPE, to form fluorinated lipoplexes. The efficiency of the fluorinated lipoplexes to transfect lung epithelial A549 cells was significantly higher than that of the DOGS lipoplexes. No specific cell toxicity was evidenced for the fluorinated lipoplexes as compared to that of the DOGS ones. The palette of structural elements explored allowed to determine those required for efficient transfection, highlighting the importance of highly fluorinated chains, the unique properties of unsaturated double-chain lipids and of the use of DOPE as helper lipid on transfection.

We report on the synthesis of a series of lipopolyamine telomers I-14,n, I-18,n, and II-18,n and on their in vitro gene-transfer capability. Their structure consists of a polyamine polar moiety, including n primary amine functions (from 1 to 70), connected to a hydrophobic moiety, including two hydrocarbon C14 or C18 chains, through a mercaptopropanoyl or mercaptoglyceryl unit and an amide or ether function. They were obtained by telomerization of N-{2-[(BOC)aminoethyl]}acrylamide with N,N-ditetradecyl- and N,N-dioctadecylpropanamide-3-thiol and rac-1,2-dioctadecyloxypropane-3-thiol, respectively, then BOC deprotection. For N/P ratios (N = number of telomer amine equivalents; P = number of DNA phosphates) from 0.8 to 10, these lipopolyamines condensed DNA, with or without the use of DOPE, forming lipopolyplexes or teloplexes of mean sizes less than 200 nm. Some trends, structure−activity and structure−toxicity relationships, were established to achieve both highest in vitro transfection levels and cell viability. Thus, DNA formulations based on telomers I-14,20 and I-18,20 and for N/P ratios lower than 5 led to the most efficient teloplex formulations for plasmid delivery to lung epithelial A549 cells.

The aim was the reconstruction of a school curriculum in reflective teaching situations within a co-operative culture. Two working assumptions were considered: (a) teacher development was based on teacher thinking and (b) school organisation followed a co-operative culture paradigm. The process features were: (a) university team consisted of external advisers; (b) school curriculum and classroom instruction were reviewed by school teachers; (c) case study as a research approach; (d) ethnographic techniques to collect data; (e) data analysis by a computer program; (f) teachers' reflective cycle to reconstruct practice; and (g) teachers' portfolios: narrative vignettes, etc. Findings showed: (a) a collaborative process school-university; (b) teachers' thinking and attitudinal change; (c) mobilisation of teachers' talents and values to work together: (i) teacher dyads to reflect on teaching; (ii) advisers' writing narrative vignettes; (Hi) collegial coaching; and (iv) curriculum materials designed by teachers. Two conclusions can be accepted: (a) teachers' pedagogical practical knowledge showed diversity of their implicit theories to design action; and (b) teachers' grounded theory confirmed that the educational action was based on a co-operative and reflective culture.

Perfluorinated glycerophosphocholine (1), which is useful as an emulsifier in fluorocarbon suspensions, was prepared in multikilogram scale in 38% overall yield. The desired phosphocholine was prepared from diacylglycerol (6) by sequential phosporylation by POCl3, reaction with choline p-toluenesulfonate, and aqueous hydrolysis. Purification was accomplished by treatment of crude 1 with ion-exchange resin. Diacylglycerol (6) was prepared by esterification of rac-1-benzyloxy-2,3-propanediol with perfluorinated acid followed by hydrogenolysis of the protective group.