Personalized Development of Antisense Oligonucleotides for Exon Skipping Restores Type XVII Collagen Expression in Junctional Epidermolysis Bullosa

Intermediate junctional epidermolysis bullosa caused by mutations in the COL17A1 gene is characterized by the frequent development of blisters and erosions on the skin and mucous membranes. The rarity of the disease and the heterogeneity of the underlying mutations renders therapy developments challenging. However, the high number of short in-frame exons facilitates the use of antisense oligonucleotides (AON) to restore collagen 17 (C17) expression by inducing exon skipping. In a personalized approach, we designed and tested three AONs in combination with a cationic liposomal carrier for their ability to induce skipping of COL17A1 exon 7 in 2D culture and in 3D skin equivalents. We show that AON-induced exon skipping excludes the targeted exon from pre-mRNA processing, which restores the reading frame, leading to the expression of a slightly truncated protein. Furthermore, the expression and correct deposition of C17 at the dermal–epidermal junction indicates its functionality. Thus, we assume AON-mediated exon skipping to be a promising tool for the treatment of junctional epidermolysis bullosa, particularly applicable in a personalized manner for rare genotypes.     

Water-soluble SG1-based alkoxyamines: A breakthrough in controlled/living free-radical polymerization in aqueous dispersed media

This feature article describes the application of nitroxide-mediated controlled/living free-radical polymerization in aqueous dispersed systems such as miniemulsion and emulsion polymerizations. It mainly focuses on the acyclic nitroxide SG1 with derived alkoxyamines and aims to show how the recent development of new water-soluble species has allowed a true emulsion polymerization process to be successfully implemented and block copolymers to be created directly in latex particles.     

Socioeconomic impacts of heat transfer research

Heat transfer research affects almost every sector of the economy, yet its impacts have not been well studied or communicated to date. To address this issue, this article evaluates recent heat transfer research trends and which parts of the economy are likely to be affected by it. Analysis is done through keywords in heat transfer journals, US NSF awards, US patents, and trends in US economic sectors. This study indicates that if heat transfer research helps to attain a 10% conversion efficiency gain in all relevant sectors of the US economy, ~ 110 billion dolars of annual value added could be generated.     

Heavy metals in marine fish meat and consumer health: a review

The numerous health benefits provided by fish consumption may be compromised by the presence of toxic metals and metalloids such as lead, cadmium, arsenic and mercury, which can have harmful effects on the human body if consumed in toxic quantities. The monitoring of metal concentrations in fish meat is therefore important to ensure compliance with food safety regulations and consequent consumer protection. The toxicity of these metals may be dependent on their chemical forms, which requires metal speciation processes for direct measurement of toxic metal species or the identification of prediction models in order to determine toxic metal forms from measured total metal concentrations. This review addresses various shortcomings in current knowledge and research on the accumulation of metal contaminants in commercially consumed marine fish globally and particularly in South Africa, affecting both the fishing industry as well as fish consumers. © 2015 Society of Chemical Industry     

Cd tolerance and accumulation in the aquatic macrophyte, Chara australis: potential use for charophytes in phytoremediation

We investigated the potential use of the alga Chara australis (R. Br.) forphytore mediation of Cd-contaminated sediments in aquatic systems. Chara tolerated up to 20 mg added Cd (kg soil)?1 in laboratory culture. Chlorophyll a and b levels were not affected even at Cd concentrations that suppressed growth. Levels of glutathione were suppressed at 2-35 mg added Cd (kg soil)?1 to 200-350 nmol GSH (g DW)?1, while control levels were 660 nmol GSH (g DW)?1). Histochemical studies showed Cd occurred throughout cell walls and cytoplasm in plants grown in 5-20 mg Cd (kg soil)?1. Quantification using ICP-MS showed the maximum concentration in shoots was 72 mg Cd (kg DW)?1 at 35 mg added Cd (kg soil)?1, while the maximum in rhizoids was 116 mg Cd (kg DW)?1 at 25 mg added Cd (kg soil)?1. The bioconcentration factor (BCF, concentration in plant/concentration in soil) exceeded 1.0, the critical value for hyperaccumulators, for shoots exposed to 35 mg Cd (kg soil)?1 and rhizoids exposed to ≥25 mg Cd (kg soil)?1. Translocation factors (TF, shoot concentration/rhizoid concentration) did not exceed 1.0 for any treatment. While Chara cannot be considered a hyperaccumulator, it shows promise for use in phytoremediation efforts.     

Mo-doped,Cr-Doped,and Mo–Cr codoped TiO2 thin-film photocatalysts by comparative sol-gel spin coating and ion implantation

Uniformly codoped anatase TiO₂ thin films of varying (equal) Mo and Cr concentrations (≤1.00 mol% for each dopant) were fabricated using sol-gel spin coating and deposited on fused silica substrates. All films were annealed at 450 °C for 2 h to recrystallise anatase. Undoped anatase films have been subjected to dual ion implantation for the first time, using Mo, Cr, and sequential Mo + Cr at 1 × 10¹⁴ atoms/cm². The films were characterised by GAXRD, AFM, SIMS, XPS, and UV–Vis and the performance was assessed by dye degradation. Despite the volumetric doping by sol-gel and the directional doping by ion implantation, neither method resulted in homogeneous dopant distributions. Both methods caused decreasing crystallinities and associated partial amorphisation. The XPS signal of the uniformly codoped films is dominated by undissolved dopant ions, which is not the case for the ion-implanted films. Increasing Ti valences are attributed to the fully oxidised condition of the Ti⁴⁺ ions that diffuse to the surface from Ti vacancy formation compared to the Ti valence of the bulk lattice, which contains Ti³⁺. Increasing O valence is attributed to the electronegativity of O^2?, which is higher than that of Ti⁴⁺. Detailed structural mechanisms for the solubility and energetics mechanisms involve the initial formation of Mo and Cr interstitials that fill the two voids adjacent to the central Ti ion in the TiO₆ octahedron, followed by integrated solid solubility (ISS) and intervalence/multivalence charge transfer (IVCT/MVCT). The sequential order of the last two is reversed for the two different doping methods. These two effects are likely to be the source of synergy, if any, between the two dopant ions. The photocatalytic performances of the uniformly codoped films are relatively poor and correlate well with the band gap (E_g). The performances of the ion-implanted films do not correlate with the E_g, where TiO₂–Mo performs poorly but TiO₂–Cr and TiO₂–Mo–Cr outperform the undoped film. These results are interpreted in terms of the competition between the effects of Mo doping, which causes partial amorphisation and/or blockage of active sites, and Cr doping, which may cause Mo–Cr synergism, Cr-based heterojunction formation, and/or improved charge-carrier separation owing to the surface-deposition nature of ion implantation.     

A survey on data fusion: what for? in what form? what is next?

Journal of Intelligent Information Systems - Data fusion is the process of merging records from multiple sources which represent the same real-world object into a single representation. This review...     

Oxygen mediated and wavelength tunable cationic photopolymerization reactions under air and low intensity: A new concept

A new concept which allows efficient cationic photopolymerization reactions under air, at any excitation wavelength in the UV–visible range and under low light intensities (conventional Xe lamp and/or laser diodes) is presented. It is based on the use of a versatile free radical promoted cationic process for the photoinitiation step which only requires a radical source, a silane and an usual iodonium salt and takes advantage of the presence of oxygen. The tunable character of the absorption is connected with the choice of the radical source. The oxygen enhancement is due to the particular role played by the silane. In every case, the silylium cation is the most efficient structure for the cationic ring opening reaction. Examples of the performance achieved (e.g. a conversion close to 100%) with such systems over the 390–580 nm range using various irradiation devices is shown and discussed.