Properties of Non-Aminoglycoside Compounds Used to Stimulate Translational Readthrough of PTC Mutations in Primary Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is a rare disease with autosomal recessive inheritance, caused mostly by bi-allelic gene mutations that impair motile cilia structure and function. Currently, there are no causal treatments for PCD. In many disease models, translational readthrough of premature termination codons (PTC-readthrough) induced by aminoglycosides has been proposed as an effective way of restoring functional protein expression and reducing disease symptoms. However, variable outcomes of pre-clinical trials and toxicity associated with long-term use of aminoglycosides prompt the search for other compounds that might overcome these problems. Because a high proportion of PCD-causing variants are nonsense mutations, readthrough therapies are an attractive option. We tested a group of chemical compounds with known PTC-readthrough potential (ataluren, azithromycin, tylosin, amlexanox, and the experimental compound TC007), collectively referred to as non-aminoglycosides (NAGs). We investigated their PTC-readthrough efficiency in six PTC mutations found in Polish PCD patients, in the context of cell and cilia health, and in comparison to the previously tested aminoglycosides. The NAGs did not compromise the viability of the primary nasal respiratory epithelial cells, and the ciliary beat frequency was retained, similar to what was observed for gentamicin. In HEK293 cells transfected with six PTC-containing inserts, the tested compounds stimulated PTC-readthrough but with lower efficiency than aminoglycosides. The study allowed us to select compounds with minimal negative impact on cell viability and function but still the potential to induce PTC-readthrough.     

Incorporation of polyfluorenes into poly(lactic acid) films for sensor and optoelectronics applications

Films of neat and plasticized biodegradable poly(lactic acid) (PLA) matrices containing anionic conjugated polyelectrolytes, poly[9,9‐bis(4‐phenoxybutylsulfonate)]fluorene‐2,7‐diyl‐alt‐arylenes, with 1,4‐phenylene and 4,4″‐p‐terphenylene, respectively, as arylene groups or a neutral poly(9,9‐dialkylfluorene) for comparison were prepared by solution casting. These films were characterized using differential scanning calorimetry, thermogravimetry, scanning electron microscopy and fluorescence spectroscopy. In addition, the effects of plasticizer on the thermal properties and the oxygen permeability of the PLA films were measured through the oxygen transmission rate. Results show that it is possible to obtain thin, optically transparent and luminescent films with potential in oxygen sensing, exhibiting good thermal and photochemical stability. At high polyelectrolyte content, evidence is found for phase separation and aggregate formation and it is no longer possible to obtain completely homogeneous films. The possibility of incorporating the cationic metal complex tris(2,2′‐bipyridyl)ruthenium(II) into plasticized PLA films containing conjugated polyelectrolytes for dual‐wavelength ratiometric luminescence sensing is also discussed. Copyright © 2012 Society of Chemical Industry     

Wideband Low‐Reflection Transmission Lines for Bare Chip on Multilayer PCB

The pad pitch of modern radio frequency integrated circuits is in the order of few tens of micrometers. Connecting a large number of high‐speed I/Os to the outside world with good signal fidelity at low cost is an extremely challenging task. To cope with this requirement, we need reflection‐free transmission lines from an on‐chip pad to on‐board SMA connectors. Such a transmission line is very hard to design due to the difference in on‐chip and on‐board feature size and the requirement for extremely large bandwidth. In this paper, we propose the use of narrow tracks close to chip and wide tracks away from the chip. This narrow‐to‐wide transition in width results in impedance discontinuity. A step change in substrate thickness is utilized to cancel the effect of the width discontinuity, thus achieving a reflection‐free microstrip. To verify the concept, several microstrips were designed on multilayer FR4 PCB without any additional manufacturing steps. The TDR measurements reveal that the impedance variation is less than 3 Ω for a 50 Ω microstrip and S11 better than –9 dB for the frequency range 1 GHz to 6 GHz when the width changes from 165 µm to 940 µm, and substrate thickness changes from 100 µm to 500 µm.     

The effect of montmorillonite and compatibilizer quantities on stiffness and toughness of polyamide nanoblends

Although polymer blend nanocomposites are widely studied, the balance between stiffness and toughness has not yet been investigated in detail. Some materials producers as well as some sectors in the automotive industry try to improve the toughness of materials without an important loss in stiffness. With this in mind, the aim of the study reported here was to obtain a good balance between toughness and stiffness of polymer blends with different amounts of clay and compatibilizer. In this context, the microstructure of polyamide 6/ethylene–propylene–diene metallocene terpolymer/(ethylene–propylene–diene copolymer)‐graft‐(maleic anhydride) blends with various amounts of clay (2, 3, 4 and 5 wt%) and compatibilizer (10 and 20 wt%) was studied to analyse the achieved morphology to understand the macroscopic properties. The morphology of the rubber phase and the dispersion of the montmorillonite (MMT) are the main factors that influence the mechanical properties. In this sense, the highest Young's modulus is achieved for nanoblends with 5 wt% of MMT, although this nanoblend has the lowest value of notched Izod impact strength. The results obtained suggest that there is a clear trade‐off between stiffness, toughness and temperature behaviour when the ratio of (ethylene–propylene–diene copolymer)‐graft‐(maleic anhydride) to MMT is 5:1. Copyright © 2009 Society of Chemical Industry     

Is the insect glutathione S-transferase I gene family intronless?

Salmonella requires its alternative sigma factor sigma S (RpoS) for virulence in mice. rpoS mutants can be frequently isolated from highly passaged Salmonella laboratory strains. In particular, the live typhoid oral vaccine Salmonella typhi Ty21a and its parental strain Ty2, a 'wild-type' strain widely used for vaccine development, are rpoS mutants. Here, we show that the nucleotide sequence of the rpoS mutant allele of Ty2 is identical to that of the rpoS mutant allele of Ty21a. This demonstrates that the rpoS mutation arose in Ty2 before the isolation of Ty21a in 1975, an observation that may have implications for vaccine research.     

Preoperative considerations with herbal medicines

More patients are using herbal remedies. Even though herbs are natural products, they often act like medications and may interact with or potentiate other medications. During a preoperative evaluation, nurses should ask patients about their use of herbal remedies. Certain herbs are dangerous and should never be taken, and others must be avoided before elective surgery. Today's perioperative health care professionals must become familiar with basic information about herbs to carry out thorough assessments. At times, caregivers may need to educate and counsel consumers about benefits and harmful aspects of herbal preparations.     

Response of microglial cells after a cryolesion in the peripheral proliferative retina of tench

We studied the glial response after inducing a lesion in the zone of the peripheral retina of tench, where there is proliferative neuroepithelium. In the retina and optic nerve, the microglial response was analysed with tomato lectin and the macroglial response with antibodies against GFAP and S-100. In lesioned retinas, there was a temporal-spatial distribution pattern of microglia. One day after lesion, primitive ramified cells appeared in the nerve fibre layer. These cells appeared progressively from the vitreal to the scleral layers until day 7 when cells appeared in all layers, with the exception of the outer plexiform layer. From this point, labelling decreased. In the optic nerve, 3 days after lesion, an increase in the number of microglial cells was observed, first in the nerve folds and from day 15 in specific areas of the optic nerve. In the central retina, in the optic nerve head and within the optic nerve itself, the appearance of microglial cells, after the lesion, near the blood vessels, could indicate a vascular origin of microglia, as has been proposed by many authors. However, we cannot discount the idea that some of the reactive microglial cells arise by proliferation of the microglia existing in the normal state. Using GFAP and S-100 antibodies, no important changes in the retina were observed, however in the optic nerve there was response to the lesion. Thus, the macroglial cells appeared to be involved in reorganisation of the optic nerve axons after lesion.