Anti-epidermal growth factor receptor siRNA carried by chitosan-transacylated lipid nanocapsules increases sensitivity of glioblastoma cells to temozolomide

Epidermal growth factor receptor (EGFR) is a crucial protein that plays an important role in the maintenance and development of glioblastomas. The silencing or knockdown of EGFR is possible by administering a small interfering ribonucleic acid (siRNA). Lipid nanocapsules (LNCs) covered by chitosan were developed in our laboratory by a transacylation process. The resulting nanocapsules have a positive zeta potential that enables electrostatic interactions with the negatively-charged siRNA. Prior to transfection, the cytotoxicity of the nanocapsules by (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS) test was performed on the U87MG cell line to determine non-toxic levels of the LNCs to avoid cell mortality. Treatment of the U87MG cells with the chitosan-transacylated LNCs/anti-EGFR siRNA complex resulted in a reduction of EGFR expression by 51.95%±6.03% (P≤0.05) after 96 hours of incubation. It also increased the cellular sensitivity to temozolomide in comparison to untreated cells with siRNA. The largest increase in mortality was 62.55%±3.55% (P<0.05). This successful knockdown provides proof for the concept of surface grafting of siRNA onto LNCs to modify cell sensitivity to temozolomide. The method could be implemented in future clinical models regarding the experimental treatment of glioblastoma cancer

Les ponts interlangues

Depuis longtemps on a rejeté l'hypothèse que l'enfant acquiert la langue par simple imitation des adultes qui l'entourent et par un conditionnement skinnerien. On considère que l'enfant écoute, découpe et analyse le langage qu'il entend et qu'il élabore une structure qui sert de base à ses propres productions. Sa restructuration du langage l'amène parfois à sur-généraliser les règles du langage adulte. On pourrait considérer que le même genre de surgénéralisation se produit chez l'enfant bilingue entre les deux langues, surtout lorsque les langues offrent des ressemblances.On a remarqué chez un enfant bilingue anglais-français (âge 4,0 à 4,9) une généralisation persistante en anglais du morphème re-, l'amenant à créer des constructions de mots en anglais illégales par rapport à la langue adulte : e.g., *reask, *rego, *recome, *refind, *reput, *recaught. On propose que ces constructions correspondent à une surgénéralisation morphologique faite par l'enfant bilingue dans sa tentative de construire des règles lui permettant d'organiser les différences et les ressemblances entre ses deux langues.The hypothesis that children learn language through simple imitation of adults has long been discarded. It rather seems that children listen and analyse the language they hear around them, and then synthesize a structure on which they base their own productions. This restructuration of language leads them, at times, to an over-generalisation of the rules of adult language. It would seem that the same type of over-generalisation is sometimes produced across the two languages of a bilingual child, especially when the languages are quite similar.A great deal of generalisation of the use of the morpheme RE- was found to occur in the English of an English-French bilingual child (age 4,0-4,9), whereby he created a number of constructions not found in adult language : e.g., *reask, *recome, *refind, *reput, *recaught, *rego. The first five of these might be considered a mapping of French onto English, but the last fits neither language. It is suggested here that these constructions represent an over-generalisation of the combinatory rules governing the creation of words with RE- as a prefix, and that their occurrence supports the hypothesis that besides rules governing each of their two languages, bilinguals also set up rules concerning differences and similarities across languages

Marker-free image registration of electron tomography tilt-series

<p>Abstract</p> <p>Background</p> <p>Tilt series are commonly used in electron tomography as a means of collecting three-dimensional information from two-dimensional projections. A common problem encountered is the projection alignment prior to 3D reconstruction. Current alignment techniques usually employ gold particles or image derived markers to correctly align the images. When these markers are not present, correlation between adjacent views is used to align them. However, sequential pairwise correlation is prone to bias and the resulting alignment is not always optimal.</p> <p>Results</p> <p>In this paper we introduce an algorithm to find regions of the tilt series which can be tracked within a subseries of the tilt series. These regions act as landmarks allowing the determination of the alignment parameters. We show our results with synthetic data as well as experimental cryo electron tomography.</p> <p>Conclusion</p> <p>Our algorithm is able to correctly align a single-tilt tomographic series without the help of fiducial markers thanks to the detection of thousands of small image patches that can be tracked over a short number of images in the series.</p

A preliminary study of genetic factors that influence susceptibility to bovine tuberculosis in the British cattle herd

Associations between specific host genes and susceptibility to Mycobacterial infections such as tuberculosis have been reported in several species. Bovine tuberculosis (bTB) impacts greatly the UK cattle industry, yet genetic predispositions have yet to be identified. We therefore used a candidate gene approach to study 384 cattle of which 160 had reacted positively to an antigenic skin test (‘reactors’). Our approach was unusual in that it used microsatellite markers, embraced high breed diversity and focused particularly on detecting genes showing heterozygote advantage, a mode of action often overlooked in SNP-based studies. A panel of neutral markers was used to control for population substructure and using a general linear model-based approach we were also able to control for age. We found that substructure was surprisingly weak and identified two genomic regions that were strongly associated with reactor status, identified by markers INRA111 and BMS2753. In general the strength of association detected tended to vary depending on whether age was included in the model. At INRA111 a single genotype appears strongly protective with an overall odds ratio of 2.2, the effect being consistent across nine diverse breeds. Our results suggest that breeding strategies could be devised that would appreciably increase genetic resistance of cattle to bTB (strictly, reduce the frequency of incidence of reactors) with implications for the current debate concerning badger-culling