Differential Micro RNA Expression in PBMC from Multiple Sclerosis Patients

Differences in gene expression patterns have been documented not only in Multiple Sclerosis patients versus healthy controls but also in the relapse of the disease. Recently a new gene expression modulator has been identified: the microRNA or miRNA. The aim of this work is to analyze the possible role of miRNAs in multiple sclerosis, focusing on the relapse stage. We have analyzed the expression patterns of 364 miRNAs in PBMC obtained from multiple sclerosis patients in relapse status, in remission status and healthy controls. The expression patterns of the miRNAs with significantly different expression were validated in an independent set of samples. In order to determine the effect of the miRNAs, the expression of some predicted target genes of these were studied by qPCR. Gene interaction networks were constructed in order to obtain a co-expression and multivariate view of the experimental data. The data analysis and later validation reveal that two miRNAs (hsa-miR-18b and hsa-miR-599) may be relevant at the time of relapse and that another miRNA (hsa-miR-96) may be involved in remission. The genes targeted by hsa-miR-96 are involved in immunological pathways as Interleukin signaling and in other pathways as wnt signaling. This work highlights the importance of miRNA expression in the molecular mechanisms implicated in the disease. Moreover, the proposed involvement of these small molecules in multiple sclerosis opens up a new therapeutic approach to explore and highlight some candidate biomarker targets in MS

A common mechanism of defective channel trafficking underlying DFNA2 hearing loss result in different cell surface expression levels of KCNQ4 mutants

KCNQ4 mutations underlie DFNA2, a subtype of autosomal dominant hearing loss. We had previously identified the pore-region p.G296S mutation that impaired channel activity in two manners: it greatly reduced surface expression and abolished channel function. Moreover, G296S mutant exerted a strong dominant-negative effect on potassium currents by reducing the channel expression at the cell surface representing the first study to identify a trafficking-dependent dominant mechanism for the loss of KCNQ4 channel function in DFNA2. Here, we have investigated the pathogenic mechanism associated with all the described KCNQ4 mutations (F182L, W242X, E260K, D262V, L274H, W276S, L281S, G285C, G285S and G321S) that are located in different domains of the channel protein. F182L mutant showed a wild type-like cell-surface distribution in transiently transfected NIH3T3 fibroblasts and the recorded currents in Xenopus oocytes resembled those of the wild-type. The remaining KCNQ4 mutants abolished potassium currents, but displayed distinct levels of defective cell-surface expression in NIH3T3 as quantified by flow citometry. Co-localization studies revealed these mutants were retained in the ER, unless W242X, which showed a clear co-localization with Golgi apparatus. Interestingly, this mutation results in a truncated KCNQ4 protein at the S5 transmembrane domain, before the pore region, that escapes the protein quality control in the ER but does not reach the cell surface at normal levels. Currently we are investigating the trafficking behaviour and electrophysiological properties of several KCNQ4 truncated proteins artificially generated in order to identify specific motifs involved in channel retention/exportation. Altogether, our results indicate that a defect in KCNQ4 trafficking is the common mechanism underlying DFNA2

Brain tissue segmentation on Diffusion Weighted Magnetic Resonance data

Introduction Diffusion weighted Imaging (DWI) techniques are able to measure, in vivo and non-invasively, the diffusivity of water molecules inside the human brain. DWI has been applied on cerebral ischemia, brain maturation, epilepsy, multiple sclerosis, etc. [1]. Nowadays, there is a very high availability of these images. DWI allows the identification of brain tissues, so its accurate segmentation is a common initial step for the referred applications. Materials and Methods We present a validation study on automated segmentation of DWI based on the Gaussian mixture and hidden Markov random field models. This methodology is widely solved with iterative conditional modes algorithm, but some studies suggest [2] that graph-cuts (GC) algorithms improve the results when initialization is not close to the final solution. We implemented a segmentation tool integrating ITK with a GC algorithm [3], and a validation software using fuzzy overlap measures [4]. Results Segmentation accuracy of each tool is tested against a gold-standard segmentation obtained from a T1 MPRAGE magnetic resonance image of the same subject, registered to the DWI space. The proposed software shows meaningful improvements by using the GC energy minimization approach on DTI and DSI (Diffusion Spectrum Imaging) data. Conclusions The brain tissues segmentation on DWI is a fundamental step on many applications. Accuracy and robustness improvements are achieved with the proposed software, with high impact on the application’s final result.

Desarrollo de un sitio web con conexión con redes sociales

La Asociación Española de Lucha contra la Esclerosis múltiple (AELEM) tiene un sitio web un poco anticuado, con información mal distribuida y acumulada toda en la sección de inicio, por lo tanto querían renovar su sitio web y conseguir otro que fuera mucho más intuitivo, que estuviera bien distribuido y que fuera más sencillo de usar para nuevos usuarios. En este contexto, el objetivo de este trabajo es desarrollar un sitio web que cumpla los nuevos requisitos de los miembros de la asociación, así como que sea más fácil para ellos mismo de administrar. Para ello a través del uso de un CMS se desarrolló un nuevo sitio web para AELEM, con nuevas funcionalidades y con las ventajas de Joomla, un CMS que pueden administrar. A través del desarrollo de diferentes componentes y módulos se consiguieron satisfacer las necesidades de los miembros de la asociación, así como se fueron añadiendo las nuevas funcionalidades que iban pidiendo a lo largo del proyecto. Los resultados obtenidos han sido muy positivos, a la junta directiva y a los miembros seleccionados de la asociación para evaluar el sitio web les ha gustado tanto la estética como la nueva distribución de la información o las nuevas funcionalidades incluidas en el sitio web, y la asociación utilizará el nuevo sitio web que se le ha desarrollado, y además con las clases que se les ha ido impartiendo podrán administrarla. ---ABSTRACT---The Spanish association of fight against the multiple sclerosis (La Asociación Española de Lucha contra la Esclerosis Multiple “AELEM”) has a fairly old fashioned website, with information poorly distributed and all accumulated in the home section. This is the reason why the association has chosen to renew its website and make a more intuitive one, with better distributed information and easier to navigate for new users. In this context, the objective of this project is to develop a new website that meets the new requirements of the association. In addition, they want a website which is easier to administrate. To archive these objectives we used a CMS to develop a new website for AELEM, with new functionalities and with the advantages of Joomla, a CMS that they can administrate. Different components and modules were developed in order to satisfy the needs of the association members and new functionalities were added as required throughout the entire project. The results we have obtained were very positive. The board of directors and the members of the association that were chosen to test the website have liked the appearance, the new distribution of the information as well as the new functionalities of the website. The association will use the new website we have developed and with the classes we have given them, they will be able to administrate it.