Human Endogenous Retrovirus HERV-Fc1 Association with Multiple Sclerosis Susceptibility: A Meta-Analysis

Background: Human endogenous retroviruses (HERVs) are repetitive sequences derived from ancestral germ-line infections by exogenous retroviruses and different HERV families have been integrated in the genome. HERV-Fc1 in chromosome X has been previously associated with multiple sclerosis (MS) in Northern European populations. Additionally, HERV-Fc1 RNA levels of expression have been found increased in plasma of MS patients with active disease. Considering the North-South latitude gradient in MS prevalence, we aimed to evaluate the role of HERV-Fc1on MS risk in three independent Spanish cohorts. Methods: A single nucleotide polymorphism near HERV-Fc1, rs391745, was genotyped by Taqman chemistry in a total of 2473 MS patients and 3031 ethnically matched controls, consecutively recruited from: Northern (569 patients and 980 controls), Central (883 patients and 692 controls) and Southern (1021 patients and 1359 controls) Spain. Our results were pooled in a meta-analysis with previously published data. Results: Significant associations of the HERV-Fc1 polymorphism with MS were observed in two Spanish cohorts and the combined meta-analysis with previous data yielded a significant association [rs391745 C-allele carriers: p(M-H) = 0.0005; ORM-H (95% CI) = 1.27 (1.11-1.45)]. Concordantly to previous findings, when the analysis was restricted to relapsing remitting and secondary progressive MS samples, a slight enhancement in the strength of the association was observed [p(M-H) = 0.0003, ORM-H (95% CI) = 1.32 (1.14-1.53)]. Conclusion: Association of the HERV-Fc1 polymorphism rs391745 with bout-onset MS susceptibility was confirmed in Southern European cohorts.

A High Degree of LINE-1 Hypomethylation Is a Unique Feature of Early-Onset Colorectal Cancer

12 p.

3D line drawing from point clouds using chromatic stereo and shading

1 PDF document (8 pp., English).-- Contributed to: VSMM'08: 14th International Conference on Virtual Systems and Multimedia (Limassol, Cyprus, Oct 20-25, 2008)

A short in-frame deletion in NTRK1 tyrosine kinase domain caused by a novel splice site mutation in a patient with congenital insensitivity to pain with anhidrosis

Background: Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive genetic disease characterized by the lack of reaction to noxious stimuli and anhidrosis. It is caused by mutations in the NTRK1 gene, which encodes the high affinity tyrosine kinase receptor I for Neurotrophic Growth Factor (NGF). -- Case Presentation: We present the case of a female patient diagnosed with CIPA at the age of 8 months. The patient is currently 6 years old and her psychomotor development conforms to her age (RMN, SPECT and psychological study are in the range of normality). PCR amplification of DNA, followed by direct sequencing, was used to investigate the presence of NTRK1 gene mutations. Reverse transcriptase (RT)-PCR amplification of RNA, followed by cloning and sequencing of isolated RT-PCR products was used to characterize the effect of the mutations on NTRK1 mRNA splicing. The clinical diagnosis of CIPA was confirmed by the detection of two splice-site mutations in NTRK1, revealing that the patient was a compound heterozygote at this gene. One of these alterations, c.574+1G > A, is located at the splice donor site of intron 5. We also found a second mutation, c.2206-2 A > G, not previously reported in the literature, which is located at the splice acceptor site of intron 16. Each parent was confirmed to be a carrier for one of the mutations by DNA sequencing analysis. It has been proposed that the c.574+1G > A mutation would cause exon 5 skipping during NTRK1 mRNA splicing. We could confirm this prediction and, more importantly, we provide evidence that the novel c.2206-2A > G mutation also disrupts normal NTRK1 splicing, leading to the use of an alternative splice acceptor site within exon 17. As a consequence, this mutation would result in the production of a mutant NTRK1 protein with a seven aminoacid in-frame deletion in its tyrosine kinase domain. --Conclusions: We present the first description of a CIPA-associated NTRK1 mutation causing a short interstitial deletion in the tyrosine kinase domain of the receptor. The possible phenotypical implications of this mutation are discussed.

Monitoring the Tension and the Temperature in an Overhead Line

MELECON 2012 - 2012 16th IEEE Mediterranean Electrotechnical Conference, 25 Mar - 28 Mar 2012, Túnez

La eficacia de la publicidad on-line en el contexto de los blogs

[ES] El objetivo del presente trabajo se ha centrado en medir la eficacia publicitaria de dos formatos de anuncios on-line, concretamente el robapáginas frente al contextual, así como los factores que sobre la base de la literatura revisada influyen en dicha eficacia publicitaria. Su contexto de aplicación son las páginas web de tipo blog o bitácora que, a pesar del auge que han experimentado en su utilización, no han recibido atención en el ámbito de la investigación publicitaria.

Model driven product line engineering : core asset and process implications

Reuse is at the heart of major improvements in productivity and quality in Software Engineering. Both Model Driven Engineering (MDE) and Software Product Line Engineering (SPLE) are software development paradigms that promote reuse. Specifically, they promote systematic reuse and a departure from craftsmanship towards an industrialization of the software development process. MDE and SPLE have established their benefits separately. Their combination, here called Model Driven Product Line Engineering (MDPLE), gathers together the advantages of both. Nevertheless, this blending requires MDE to be recasted in SPLE terms. This has implications on both the core assets and the software development process. The challenges are twofold: (i) models become central core assets from which products are obtained and (ii) the software development process needs to cater for the changes that SPLE and MDE introduce. This dissertation proposes a solution to the first challenge following a feature oriented approach, with an emphasis on reuse and early detection of inconsistencies. The second part is dedicated to assembly processes, a clear example of the complexity MDPLE introduces in software development processes. This work advocates for a new discipline inside the general software development process, i.e., the Assembly Plan Management, which raises the abstraction level and increases reuse in such processes. Different case studies illustrate the presented ideas.

Role of G protein coupled inwardly rectifier K+ channels (GIRK) on the neurobiology depression

353 págs.

Clinical factors associated with a Candida albicans Germ Tube Antibody positive test in Intensive Care Unit patients

Background: Poor outcomes of invasive candidiasis (IC) are associated with the difficulty in establishing the microbiological diagnosis at an early stage. New scores and laboratory tests have been developed in order to make an early therapeutic intervention in an attempt to reduce the high mortality associated with invasive fungal infections. Candida albicans IFA IgG has been recently commercialized for germ tube antibody detection (CAGTA). This test provides a rapid and simple diagnosis of IC (84.4% sensitivity and 94.7% specificity). The aim of this study is to identify the patients who could be benefited by the use of CAGTA test in critical care setting. Methods: A prospective, cohort, observational multicentre study was carried out in six medical/surgical Intensive care units (ICU) of tertiary-care Spanish hospitals. Candida albicans Germ Tube Antibody test was performed twice a week if predetermined risk factors were present, and serologically demonstrated candidiasis was considered if the testing serum dilution was >= 1: 160 in at least one sample and no other microbiological evidence of invasive candidiasis was found. Results: Fifty-three critically ill non-neutropenic patients (37.7% post surgery) were included. Twenty-two patients (41.5%) had CAGTA-positive results, none of them with positive blood culture for Candida. Neither corrected colonization index nor antifungal treatment had influence on CAGTA results. This finding could corroborate that the CAGTA may be an important biomarker to distinguish between colonization and infection in these patients. The presence of acute renal failure at the beginning of the study was more frequent in CAGTA-negative patients. Previous surgery was statistically more frequent in CAGTA-positive patients. Conclusions: This study identified previous surgery as the principal clinical factor associated with CAGTA-positive results and emphasises the utility of this promising technique, which was not influenced by high Candida colonization or antifungal treatment. Our results suggest that detection of CAGTA may be important for the diagnosis of invasive candidiasis in surgical patients admitted in ICU.

Estrategias de lectura on-line en inglés como lengua extranjera

XXIV, 508 p.

Desarrollo de componentes para el panel de administración de GeoServicios® on-line

Panel de Administración que ofrece una solución completa a la hora de realizar visores para mapas y que permite al cliente configurar un visor en base a sus necesidades, mediante diferentes módulos. Dicho panel, se ha realizado utilizando un desarrollo basado en el prototipado. En el caso de este proyecto, se especifica el desarrollo de los dos primeros prototipos. Los módulos desarrollados son los siguientes: Panel de login: Este panel permite el acceso a la aplicación. Módulo de usuarios/grupos: Este componente permite gestionar grupos y usuarios, tanto la creación, edición de los mismos como la visualización de estos. Módulo de datos: Este componente permite gestionar las fuentes de datos del cliente. Crear plantillas a partir de datos procedentes de BBDD propias, así como la edición de dichas plantillas. Módulo GeoAsset: Este componente permite configurar aplicaciones web o visores. Un visor tendrá asociado un mapa, una lista de control de accesos, etc. Siguiendo la estructura de módulos, también es objeto del proyecto la realización de un segundo prototipo que contiene la mejora de uno de los módulos ya creados: Mejora de módulo de datos: Este componente implementa además de las funcionalidades creadas en la anterior versión, una funcionalidad para permitir la subida de datos a la aplicación.

Efectos de la interacción entre las respuestas emocionales hacia anuncios publicitarios y contenidos generados por los usuarios en redes sociales on-line

Máster en Dirección Empresarial desde la Innovación y la Internacionalización. Curso 2013/2014

Advantages and Versatility of Fluorescence-Based Methodology to Characterize the Functionality of LDLR and Class Mutation Assignment

Familial hypercholesterolemia (FH) is a common autosomal codominant disease with a frequency of 1:500 individuals in its heterozygous form. The genetic basis of FH is most commonly mutations within the LDLR gene. Assessing the pathogenicity of LDLR variants is particularly important to give a patient a definitive diagnosis of FH. Current studies of LDLR activity ex vivo are based on the analysis of I-125-labeled lipoproteins (reference method) or fluorescent-labelled LDL. The main purpose of this study was to compare the effectiveness of these two methods to assess LDLR functionality in order to validate a functional assay to analyse LDLR mutations. LDLR activity of different variants has been studied by flow cytometry using FITC-labelled LDL and compared with studies performed previously with I-125-labeled lipoproteins. Flow cytometry results are in full agreement with the data obtained by the I-125 methodology. Additionally confocal microscopy allowed the assignment of different class mutation to the variants assayed. Use of fluorescence yielded similar results than I-125-labeled lipoproteins concerning LDLR activity determination, and also allows class mutation classification. The use of FITC-labelled LDL is easier in handling and disposal, cheaper than radioactivity and can be routinely performed by any group doing LDLR functional validations.

Epitope mapping of antibodies to alpha-synuclein in LRRK2 mutation carriers, idiopathic Parkinson disease patients, and healthy controls

Alpha-synuclein (Snca) plays a major role in Parkinson disease (PD). Circulating anti-Snca antibodies has been described in PD patients and healthy controls, but they have been poorly characterized. This study was designed to assess the prevalence of anti-Snca reactivity in human subjects carrying the LRRK2 mutation, idiopathic PD (iPD) patients, and healthy controls and to map the epitopes of the anti-Snca antibodies. Antibodies to Snca were detected by ELISA and immunoblotting using purified recombinant Snca in plasma from individuals carrying LRRK2 mutations (104), iPD patients (59), and healthy controls (83). Epitopes of antibodies were mapped using recombinant protein constructs comprising different regions of Snca. Clear positive anti-Snca reactivity showed no correlation with age, sex, years of evolution, or the disability scores for PD patients and anti-Snca reactivity was not prevalent in human patients with other neurological or autoimmune diseases. Thirteen of the positive individuals were carriers of LRRK2 mutations either non-manifesting (8 out 49 screened) or manifesting (5 positive out 55), three positive (out of 59) were iPD patients, and five positive (out of 83) were healthy controls. Epitope mapping showed that antibodies against the N-terminal (a.a. 1-60) or C-terminal (a.a. 109-140) regions of Snca predominate in LRRK2 mutation carriers and iPD patients, being N122 a critical amino acid for recognition by the anti-C-terminal directed antibodies. Anti-Snca circulating antibodies seem to cluster within families carrying the LRRK2 mutation indicating possible genetic or common environmental factors in the generation of anti-Snca antibodies. These results suggest that case-controls' studies are insufficient and further studies in family cohorts of patients and healthy controls should be undertaken, to progress in the understanding of the possible relationship of anti-Snca antibodies and PD patholog

Errugbiko line-out jaurtiketaren abiaduren analisia eta jaurtitzaileen potentzia eta zehaztasunaren arteko erlazioa.

Hurrengo ikerketan errugbiko line out baten jaurtiketaren abiaduraren analisia eta jaukitzaileen baloia abiadura altuan jaurtitzeko ahalmena, zehaztasunarekin ikertuko da. Hamazortzi eta hogeita bi urte tarteko errugbi jokalariak egin zituzten frogak, partaideak froga bakarra egin zuten denboraldiaren hasieran, aurre-denboraldiaren amaieran. Jokalarien arteko konparaketa egin zen. Ikertuko diren aldagarriak, eta jaurtitzaileen ahalmena neurtzen dutenak hurrengoak dira: abiadura eta zehaztasuna. bi abiadura ezberdin kalkulatu egin dira, bata helburu zehatz batekin eta bestea helburu zehatzik gabe, horrela potentzia guztia ikusi ahal izateko. Bi abiadurak konparatuz beste aldagarri bat atera da, %galera izenekoa, aldagarri onek bi abiaduraren arteko ezberdintasuna adierazten du.