Ribbon-like Foldamers for Cellular Uptake and Drug Delivery

Different intracellular delivery systems of bioactive compounds have been developed, including cell-penetrating peptides. Although usually nontoxic and biocompatible, these vectors share some of the general drawbacks of peptides, notably low bioavailability and susceptibility to protease degradation, that limit their use. Herein, the conversion of short peptide sequences into poly-α-amino-γ-lactam foldamers that adopt a ribbon-like structure is investigated. This template is used to distribute critical cationic and/or hydrophobic groups on both sides of the backbone, leading to potent short, cell-permeable foldamers with a low positive-charge content. The lead compound showed dramatically improved protease resistance and was able to efficiently deliver a biologically relevant cargo inside cells. This study provided a simple strategy to convert short peptide sequences into efficient protease-resistant cell-penetrating foldamers.     

Luminescence nanothermometry with alkyl-capped silicon nanoparticles dispersed in nonpolar liquids

Silicon nanoparticles (Si NPs) with a diameter size ranging from 4 to 8 nm were successfully fabricated. They exhibit a visible photoluminescence (PL) due to the quantum confinement effect. Chemical functionalization of these Si NPs with alkyl groups allowed to homogeneously disperse them in nonpolar liquids (NPLs). In comparison to most of literature results for Si NPs, an important PL peak position variation with temperature (almost 1 meV/K) was obtained from 303 to 390 K. The influence of the liquid viscosity on the peak positions is also presented. These variations are discussed considering energy transfer between nanoparticles. The high PL thermal sensitivity of the alkyl-capped Si NPs paves the way for their future application as nanothermometers.     

Regulation and perturbation of testicular functions by vitamin A

In addition to playing a fundamental role in very diverse processes such as vision and the growth and differentiation of numerous types of cell, vitamin A (retinol) and its principal biologically active derivative, retinoic acid, are clearly involved in the regulation of testicular functions in rodents. An excess of vitamin A leads to testicular lesions and spermatogenetic disorders, and a deficiency induces early cessation of spermatogenesis and adversely affects testosterone secretion. Furthermore, mice mutant for retinoic acid alpha receptors and retinoid X beta receptors are sterile. Retinoids appear to exert an action on the three main testicular types of cell (Sertoli, germinal and Leydig cells), as they act on the signalling pathways and Sertoli cell metabolism, and modify numerous factors secreted in Sertoli cells. Retinoids also appear to be necessary for the proliferation and differentiation of A spermatogonia, and for spermiogenesis. In addition, vitamin A deficiency leads to atrophy of the accessory sex organs after decreased testosterone production. Recent studies have shown that retinoids already affect these three types of cell in fetuses. Curiously, the effects of retinoids on fetal and adult testis seem opposed.     

Numerical simulation of the viscous shock tube problem by using a high resolution monotonicity-preserving scheme

This work deals with the flow generated in a shock tube after the shock wave has reflected at the end wall. For a viscous fluid, a complex unsteady interaction takes place between the incident boundary layer and reflected shock wave. The numerical simulation of this complex flow requires both robust and accurate numerical schemes. In this work, we rely on the one-step high-order scheme recently proposed by Daru and Tenaud [Daru V, Tenaud C. High order one-step monotonicity preserving schemes for unsteady flow calculations. J Comput Phys 2004;193:563-94]. With this scheme, converged results are obtained for Reynolds numbers in the range 200-1000. The interaction mechanisms are carefully analyzed as well as the flow dynamics.     

Network Rearrangement in AgI‐Doped GeTe4 Glasses

The structure of (GeTe₄)_1?x(AgI)_x (x = 0.15 and 0.25) glasses has been investigated by X‐ray and neutron diffraction as well as extended X‐ray absorption spectroscopy (EXAFS) and Raman spectroscopy. Large‐scale structural models have been obtained by fitting simultaneously the experimental datasets in the framework of the reverse Monte Carlo simulation technique (RMC). Short‐range order parameters have been calculated and compared with that of GeTe₄. Doping with AgI affects the structure of the host GeTe₄ matrix in two ways. First, while Te is essentially twofold coordinated in GeTe_4, its coordination number is as high as ~2.9 ± 0.3 for x = 0.25. The change is mainly due to the increased fraction of Te–Te bonds. Second, Ge atoms remain fourfold coordinated but the tetrahedral symmetry is distorted due to the elongation of some Ge–Te bonds. The incorporation of AgI in the GeTe₄‐based host covalent matrix and the Te coordination increase explains the enhanced thermal stability of (GeTe₄)_1?x(AgI)_x in the supercooled liquid‐state hindering the crystallization of Te found in case of GeTe₄ glass.     

A high-throughput mutation detection method based on heteroduplex analysis using graft copolymer matrixes: application to Brca1 and Brca2 analysis

We present here a new approach to electrophoretic heteroduplex analysis (EHDA) based on improved matrixes. EHDA is an appealing technique for the detection of unknown point mutations because of its simplicity and high throughput. We present here a new matrix for electrophoretic heteroduplex analysis much more sensitive for insertions, deletions, and substitutions than reported for previous EHDA separations and also superior to DHPLC. This separation matrix is based on a copolymer with a comb architecture, poly(acrylamide-g-polydimethylacrylamide), made of a high molecular weight polyacrylamide backbone grafted with poly(dimethylacrylamide) side chains. The effect of operational parameters on electrophoretic resolution and sensitivity to single-nucleotide mismatches was studied using a collection of samples from patients bearing mutations in the breast cancer predisposition genes BRCA1 and BRCA2. Seventeen fragments (10 mutations), implying mostly substitutions on fragments with sizes ranging from 200 to 600 bp, were analyzed using a single set of separation conditions. A success rate of 94% was achieved with a qualitative analysis in terms of number of peaks, and 100% identification of mutations was obtained with a more quantitative test using peak width analysis. This strong improvement of performance with regard to previous HDA methods is attributed to a composite mechanism of separation, combining steric and chromatographic effects. It opens the route to a significant reduction of development time and operation cost for diagnostic and genomic applications.     

Distance dependence of the Surface Enhanced Raman Scattering effect observed in amorphous TiO2 on nanostructured gold

Plasmon resonance of gold nanoparticles is responsible of the electromagnetic (EM) Surface Enhanced Raman Scattering (SERS) effect. Interaction of an amorphous matrix with a SERS substrate was studied. Thin films with different thickness of amorphous TiO₂ coated on a Klarite® substrate show a 100 times enhancement of the Raman signal. Distance dependence of the SERS interaction was shown to be less than 60 nm.     

Process improvement for semipurified oleosomes on a pilot-plant scale

Semipurified oleosomes were isolated on a pilot-plant scale using improved-process extraction conditions. The improved process consisted of continuous centrifugation in a three-phase decanter with recirculation of slurry until most of the oleosomes were recovered. Oleosome fractionation, oleosin identification, and isoflavone and saponin mass distributions and recoveries were investigated. The improved pilot-plant oleosome extraction process was achieved in 8 h. A total of 91%± 1% of soybean oil was recovered as intact oleosomes. The oil content of the aqueous supernatant and the residue fractions were low at 2% and 3%, respectively. The aqueous supernatant fraction contained 40% total soybean protein. About 76% of the proteins present in the oleosome fraction were soybean storage proteins. Washing the semipurified oleosomes with a 0.1 M Tris-HCl, pH 8.6 containing 0.4 M sucrose, and 0.5 M NaCl resulted in the recovery of the associated storage proteins. The recovery of these proteins in addition to the protein in aqueous supernatant accounted for 79% of the total soybean storage proteins fractionated by this process. Oleosins were detected at 17 and 18 kDa. Isoflavones and saponins partitioned into the oleosome, aqueous supernatant, and residue fractions at different ratios with the majority, about 82 and 63 mole%, respectively, in oleosome and aqueous supernatant fractions, making these fractions an attractive source for phytochemicals.