Nanofilm biomaterials: localized cross-linking to optimize mechanical rigidity and bioactivity

Nanofilm biomaterials, formed by the layer-by-layer assembly of charged macromolecules, are important systems for a variety of cell-contacting biomedical and biotechnological applications. Mechanical rigidity and bioactivity are two key film properties influencing the behavior of contacting cells. Increased rigidity tends to improve cells attachment, and films may be rendered bioactive through the incorporation of proteins, peptides, or drugs. A key challenge is to realize films that are simultaneously rigid and bioactive. Chemical cross-linking of the polymer framework--the standard means of increasing a film's rigidity--can diminish bioactivity through deactivation or isolation of embedded biomolecules or inhibition of film biodegradation. We present here a strategy to decouple mechanical rigidity and bioactivity, potentially enabling nanofilm biomaterials that are both mechanically rigid and bioactive. Our idea is to selectively cross-link the outer region of the film, resulting in a rigid outer skin to promote cell attachment, while leaving the film interior (with any embedded bioactive species) unaffected. We propose an approach whereby an N-hydroxysulfosuccinimide (sulfo-NHS) activated poly(L-glutamic acid) is added as the terminal layer of a multilayer film and forms (covalent) amide bonds with amino groups of poly(L-lysine) placed previously within the film. We characterize film assembly and cross-linking extent via quartz crystal microbalance with dissipation monitoring (QCMD), Fourier transform infrared spectroscopy in attenuated total reflection mode (FTIR-ATR), and laser scanning confocal microscopy (LSCM) and measure the attachment and metabolic activity of preosteoblastic MC3T3-E1 cells. We show cross-linking to occur primarily at the film surface and the subsequent cell attachment and metabolic activity to be enhanced compared to native films. Our method appears promising as a means to realize films that are simultaneously mechanically rigid and bioactive.     

Maternal obesity does not influence human milk protein 15N natural isotope abundance

ABSTRACT

Obesity increases protein metabolism with a potential effect on nitrogen isotope fractionation. The aim of this study was to test the influence of obesity on human milk extracted protein ¹⁵N natural isotope abundance (NIA) at one month post-partum and to compare human milk extracted protein ¹⁵N NIA and bulk infant hair ¹⁵N NIA. This cross-sectional observational study involved 16 obese mothers (body mass index (BMI)?≥?30?kg?m^?2 before pregnancy) matched with 16 normal-weight mothers (18.5?kg?m^?2?≤?BMI?<?25?kg?m^?2) for age and pregnancy characteristics. Human milk extracted protein and bulk infant hair ¹⁵N NIA were determined by isotope ratio monitoring by mass spectrometry interfaced to an elemental analyser (IRM-EA/MS). No significant difference was found in human milk protein ¹⁵N NIA values between obese and normal-weight mothers (8.93?±?0.48?‰ vs. 8.95?±?0.27?‰). However, human milk protein ¹⁵N NIA was significantly lower than bulk infant hair ¹⁵N NIA: 8.94?±?0.38?‰ vs. 9.66?±?0.69?‰, respectively. On the basis of these results, it is concluded that human milk protein ¹⁵N NIA measured at one month post-partum is not influenced by maternal obesity. These findings suggest that ¹⁵N NIA may be exploited to study metabolism without considering maternal obesity as a confounder.     

α,α-Difluorophosphonohydroxamic Acid Derivatives among the Best Antibacterial Fosmidomycin Analogues

Three α,α-difluorophosphonate derivatives of fosmidomycin were synthesized from diethyl 1,1-difluorobut-3-enylphosphonate and were evaluated on Escherichia coli. Two of them are among the best 1-deoxy-d-xylulose 5-phosphate reductoisomerase inhibitors, with IC₅₀ in the nM range, much better than fosmidomycin, the reference compound. They also showed an enhanced antimicrobial activity against E. coli on Petri dishes in comparison with the corresponding phosphates and the non-fluorinated phosphonate.     

Thermal and Structural Behavior of Palm Oil. Influence of Cooling Rate on Fat Crystallization

Summary: The effects of scanning rates (q = −0.5 °C/min to −50 °C/min) on the formation of the different phases occurring at low temperature of a palm oil are investigated by means of calorimetry and optical analysis. It is demonstrated that the cooling rates changed the polymorphism of triacylglycerols (TAGs). The centrifugation is used to separate the two fractions (olein and stearin) of palm oil. We show whereas the rate of centrifugation the separation is not effective. We obtained two fractions, a liquid fraction and a solid fraction which contains some liquid TAGs. It is observed that the solid fraction of palm oil is more sensitive to the effects of the cooling rates. By changing the cooling rate q, it appears threshold behaviour for q = −3 °C/min dividing the data discussion in two parts: for slow cooling rate and for fast cooling rate. At slow cooling rates, TAGs had more time to interact. Contrary at fast cooling rate, TAGs have not the time to be reorganised in more stable conformation. Micrographs revealed that the types of crystals observed were spherolites but some variations in crystal size appeared with the variation of cooling rate.     

Fast data preprocessing for chromatographic fingerprints of tomato cell wall polysaccharides using chemometric methods

The variability in the chemistry of cell wall polysaccharides in pericarp tissue of red-ripe tomato fruit (Solanum lycopersicon Mill.) was characterized by chemical methods and enzymatic degradations coupled to high performance anion exchange chromatography (HPAEC) and mass spectrometry analysis. Large fruited line, Levovil (LEV) carrying introgressed chromosome fragments from a cherry tomato line Cervil (CER) on chromosomes 4 (LC4), 9 (LC9), or on chromosomes 1, 2, 4 and 9 (LCX) and containing quantitative trait loci (QTLs) for texture traits, was studied. In order to differentiate cell wall polysaccharide modifications in the tomato fruit collection by multivariate analysis, chromatograms were corrected for baseline drift and shift of the component elution time using an approach derived from image analysis and mathematical morphology. The baseline was first corrected by using a "moving window" approach while the peak-matching method developed was based upon location of peaks as local maxima within a window of a definite size. The fast chromatographic data preprocessing proposed was a prerequisite for the different chemometric treatments, such as variance and principal component analysis applied herein to the analysis. Applied to the tomato collection, the combined enzymatic degradations and HPAEC analyses revealed that the firm LCX and CER genotypes showed a higher proportion of glucuronoxylans and pectic arabinan side chains while the mealy LC9 genotype demonstrated the highest content of pectic galactan side chains. QTLs on tomato chromosomes 1, 2, 4 and 9 contain important genes controlling glucuronoxylan and pectic neutral side chains biosynthesis and/or metabolism.     

Both water- and organo-soluble supramolecular polymer stabilized by hydrogen-bonding and hydrophobic interactions

A new bis-urea based supramolecular polymer is reported and shown by viscosimetry, neutron scattering (SANS), and calorimetry (ITC) to self-assemble in a wide range of solvents, encompassing the polarity scale from water to toluene. The presence of both hydrogen-bonding and hydrophobic groups ensures that self-assembly occurs in water, aprotic polar solvents, and nonpolar solvents. Both the driving force for the assembly and the exact structure of the filaments is solvent dependent, but whatever the solvent, long rigid filaments are formed in dynamic equilibrium with the monomer.     

Design of Blends with an Extremely Low Viscosity Ratio between the Dispersed and Continuous Phases. Dependence of the Dispersed Phase Size on the Processing Parameters

Summary: This work deals with the development of the dispersed phase morphology in immiscible blends of poly(ethylene glycol)/polyamide 66 (PEG/PA) with an extremely low viscosity ratio. The blends were obtained, under different operating conditions, by melt blending in an internal mixer. The objective was to examine the influence of the main processing parameters on the particles size of the minor phase (PEG). A model was elaborated to describe the dependence of the particle size on interfacial tension, PEG concentration, shear rate and viscosity ratio between the two blend components.     

Synthesis and Kinase Inhibitory Potencies of Pyrazolo[3,4-g]isoquinolines

A new series of pyrazolo[3,4-g]isoquinoline derivatives, diversely substituted at the 4- or 8-position, were synthesized. The results of the kinase inhibitory potency study demonstrated that the introduction of a bromine atom at the 8-position was detrimental to Haspin inhibition, while the introduction of an alkyl group at the 4-position led to a modification of the kinase inhibition profiles. Altogether, the results obtained demonstrated that new pyrazolo[3,4-g]isoquinolines represent a novel family of kinase inhibitors with various selectivity profiles.