Emerging Gene Correction Strategies for Muscular Dystrophies: Scientific Progress and Regulatory Impact

Muscular dystrophies comprise a heterogeneous cluster of inherited muscle degenerative disorders with the common feature of progressive muscle weakness. These represent good candidates for treatment with gene-based therapies. Progress in gene transfer technologies has raised hopes for successful therapeutic restoration of mutated genes such as dystrophin in Duchenne muscular dystrophy. Delivery to enough muscle cells, however, remains a challenge for a successful gene replacement therapy. Other approaches based on exon skipping to correct mutant dystrophin’s pre-mRNA splicing patterns have been tried, and partial restoration of dystrophin expression was reported in late-stage clinical trials, but full therapeutic efficacy is yet to be confirmed. The emergence of gene editing and its recent success in AIDS have opened a new therapeutic era for muscular dystrophies. This chapter will cover new gene correction strategies for muscular dystrophies and their regulatory challenges before they can become routine treatment modalities in the clinic

An optical fibre switch employing a Sagnac interferometer

Local area networks and high-bit-rate telecommunications demand fast switches for modulators, re-routing and demultiplexing. Optically-driven nonlinear optical switches based on intensity-dependent phase shifts in an optical fibre have been demonstrated at femtosecond switching speeds. An all optical switch has the benefit of compatibility with the rest of the optical network and its availability would considerably enhance the capabilities of optical transmission systems. An optical fibre switch which exploits the non-linearity in silica fibre may be polarimetric or interferometric. However, most configurations are very environmentally unstable and suffer large phase shifts due to temperature and vibration. The exception is the Sagnac interferometer, which uses the same path for both interfering beams and is therefore only sensitive to perturbations that occur in a time less than the loop transit time. We describe here the basic theory of operation of the Sagnac fibre switch, followed by an experimental demonstration of a stable switch operating on a picosecond time scale

Untersuchungen zur acetonämie bei der milchkuh

International audienc

Phenotypic Characterisation of Clostridium Difficile Strains Defective in Lipoprotein Biosynthesis

Clostridium difficile is regarded as the primary etiological agent of antibiotic - associated diarrhoea, posing a significant challenge to healthcare facilities. The changing nature of C. difficile infection is causing an increase in associated disease occurrence outside of the healthcare setting and a gradual move away from the historical association with antimicrobial treatment. Adhesio n of spores and vegetative cells to host gut epithelium is thought to be a key aspect of C. difficile virulence; disruption of this process may significantly reduce the impact of an infection and the likelihood of infection spread. Lipoproteins are involve d in adhesion of C. difficile to host tissues and may have roles in other key aspects of virulence. Lipoproteins undergo a specific biosynthesis process within the bacterial cell involving addition of an acyl - glyceryl moiety by lipoprotein glyceryl transfe rase (Lgt) followed by signal peptide cleavage by lipoprotein signal peptidase (LspA); disruption of this process may cause attenuation of virulence and a reduction in adhesion to host tissue . C. difficile has been shown to encode two functional and homolo gous lipoprotein signal peptidases: LspA and LspA2. The novel antimicrobials globomycin and myxovirescin directly target lipoprotein signal peptidases and therefore may have potential for use in treatment of C. difficile infection. Evaluation of their effi cacy against LspA and LspA2 can be determined by protection assays using Escherichia coli strains expressing LspA or LspA2 from C. difficile . In this study, both LspA and LspA2 from C. difficile are shown to contain the consensus sequences, domains and in silico predicted tertiary structure expected of lipoprotein signal peptidases. Characteris ation of C. difficile strains with silencing mutations in either lspA or lspA2 , in comparison to a wild type , reveals that the absence of either lipoprotein signal pe ptidase causes an increased survivability in hydrogen peroxide and may affect protein localis ation within the bacterium. Finally, successful cloning of C. difficile lspA and lspA2 and subsequent expression of LspA and LspA2 via auto - induction in E. coli is reported, paving the way for further investigation into the effect of globomycin or myxovirescin treatment

The influence of nutrition (energy and digestible crude protein) on some blood parameters, health and fertility in late pregnant milking cows

International audienc

Spectroscopic and lasing characteristics of samarium-doped glass fibre

The fluorescence spectra of trivalent samarium doped glass fibres are described. In silica glass Sm3+ has a narrow fluorescence of 2.2 nm f.w.h.m. at a wavelength of 650 nm The influence of fluorescence line narrowing and large external electric fields on this line is reported. Visible laser emission is obtained at this wavelength when the fibre is pumped in a Fabry Perot cavity. The performance of the laser in continuous, Q-switched and self mode-locked operation is described. The basic theory of self-mode-locking is presented