SELECTIVIDAD DE LAS ISOFORMAS DE 140-180 KDA DE NCAM EN LA PAPILA ÓPTICA DEL EMBRIÓN DE POLLO

During embryonic development of chicken retina and retinotectal proyection, neural cells showed spatiotemporal patterns in the glycosidic residues located in the plasmatic membranes. Those glycidic components are related with adhesion and recognition cellular behaviours during the generation of nervous system cytoarchitecture. Thus those sugars are included both in usual glycoproteins as in a group of molecules called as cell adhesion molecules (CAM). The first isolated molecule in this group was the neural cell adhesion molecule (NCAM). This glycoprotein has a proteic core with diverse isoforms and it has a variable sialic acids chain. It was able to determine that 120 kDa NCAM isoform shows scarcely sialized chains in intermediate stages by using conventional techniques, lectins and immunohistochemistry. Meanwhile 140-180 kDa NCAM isoforms possess high content in sialic acid and they are present both in early and final stages. Other authors reported that human 120 kDa NCAM isoform was similar to that observed in the Gallus domesticus retina. Our results showed that 140- 180kDa isoforms were only presented in the nerve optic fibers when they were left the optic disc.Durante la embriogénesis de la retina del Gallus domesticus, los neuroblastos muestran variaciones temporales y espaciales de los residuos glucosilados a nivel de sus membranas plasmáticas. Se considera que estos componentes glucídicos están implicados en la organización de estructuras neurales inmaduras, mediante su participación en mecanismos de reconocimiento y adhesión celulares. Los componentes glucosilados van a formar parte de glucoproteínas convencionales, así como de un grupo de moléculas a las que genéricamente se han denominado moléculas de adhesión celular. La primera de estas moléculas aislada fue la neural cell adhesion molecule (NCAM), glucoproteína compuesta por un armazón proteico con diversas isoformas y una cadena más o menos variable de polímeros de ácidos siálicos. La combinación de técnicas convencionales his- toquímicas, de lectinas e inmunocitoquímicas han permitido determinar que las moléculas de NCAM de 120 kDa presentan cadenas pobremente sializadas en estadíos intermedios del desarrollo, mientras en estadíos tempranos y finales los ácidos siálicos están más abundantemente representados en las isoformas de 140-180 kDa. Algunos autores han determinado que la isoforma de NCAM presente durante el desarrollo de la retina del Gallus domesticus es similar a la humana de 120 kDa. Nuestros resultados indican que las isoformas de 140-180 kDa sólo se presentan en las fibras del nervio óptico una vez que estas abandonan la papila óptica

X-chromosome tiling path array detection of copy number variants in patients with chromosome X-linked mental retardation

Contiene 3 ficheros adicionales con información suplementaria.-- et al.[Background] Aproximately 5–10% of cases of mental retardation in males are due to copy number variations (CNV) on the X chromosome. Novel technologies, such as array comparative genomic hybridization (aCGH), may help to uncover cryptic rearrangements in X-linked mental retardation (XLMR) patients. We have constructed an X-chromosome tiling path array using bacterial artificial chromosomes (BACs) and validated it using samples with cytogenetically defined copy number changes. We have studied 54 patients with idiopathic mental retardation and 20 controls subjects.[Results] Known genomic aberrations were reliably detected on the array and eight novel submicroscopic imbalances, likely causative for the mental retardation (MR) phenotype, were detected. Putatively pathogenic rearrangements included three deletions and five duplications (ranging between 82 kb to one Mb), all but two affecting genes previously known to be responsible for XLMR. Additionally, we describe different CNV regions with significant different frequencies in XLMR and control subjects (44% vs. 20%).[Conclusion] This tiling path array of the human X chromosome has proven successful for the detection and characterization of known rearrangements and novel CNVs in XLMR patients.The authors thank the "Genoma España" and Genome Canada joint R+D+I projects in human health, plants and aquiculture; the former "Departament d'Universitats i Societat de la Informació" (DURSI) and the "Departament de Salut", from the Catalan Autonomous Government (2005SGR00008 - Generalitat de Catalunya); the Instituto de Salud Carlos III (PI041126, CIBER-ESP), the EU's Sixth Framework Programme [FP6-2005-LIFESCIHEALTH-7; ANEUPLOIDY No. 037627] and Fundación Areces (U-2006-FARECES-O).Peer reviewe

The HIV/AIDS epidemic in Cuba: description and tentative explanation of its low HIV prevalence

<p>Abstract</p> <p>Background</p> <p>The Cuban HIV/AIDS epidemic has the lowest prevalence rate of the Caribbean region. The objective of this paper is to give an overview of the HIV/AIDS epidemic in Cuba and to explore the reasons for this low prevalence.</p> <p>Methods</p> <p>Data were obtained from the Cuban HIV/AIDS programme established in 1983. This programme has an extensive adult HIV testing policy, including testing of all pregnant women. HIV and AIDS cases have been recorded since 1986. Persons found to be HIV-positive are interviewed on their sexual behaviour and partners. Tracing and voluntary testing of these partners are organised. Epidemiological description of this epidemic was obtained from analysis of this data set. Using elementary mathematical analyses, we estimated the coverage of the detection system (percentage of HIV-positive adults detected) and the average period between HIV infection and detection. Estimated HIV prevalence rates were corrected to account for the coverage.</p> <p>Results</p> <p>HIV prevalence has increased since 1996. In 2005, the prevalence among pregnant women was 1.2 per 10,000 (16/137000). Estimated HIV prevalence among 15- to 49-year-olds was 8.1 per 10,000 (4913/6065000; 95%CI: 7.9 per 10,000 – 8.3 per 10,000). Most (77%) of the HIV-positive adults were men, most (85.1%) of the detected HIV-positive men were reported as having sex with men (MSM), and most of the HIV-positive women reported having had sex with MSM. The average period between HIV infection and detection was estimated to be 2.1 years (IQR = 1.7 – 2.2 years). We estimated that, for the year 2005, 79.6% (IQR: 77.3 – 81.4%) of the HIV-positive persons were detected.</p> <p>Conclusion</p> <p>MSM drive the HIV epidemic in Cuba. The extensive HIV testing policy may be an important factor in explaining the low HIV prevalence. To reduce the HIV epidemic in Cuba, the epidemic among MSM should be addressed. To understand this epidemic further, data on sexual behaviour should be collected. Now that antiretroviral therapy is more widely available, the Cuban policy, based on intensive HIV testing and tracing of partners, may be considered as a possible policy to control HIV/AIDS epidemics in other countries.</p

The Phyre2 web portal for protein modeling, prediction and analysis

Phyre2 is a suite of tools available on the web to predict and analyze protein structure, function and mutations. The focus of Phyre2 is to provide biologists with a simple and intuitive interface to state-of-the-art protein bioinformatics tools. Phyre2 replaces Phyre, the original version of the server for which we previously published a paper in Nature Protocols. In this updated protocol, we describe Phyre2, which uses advanced remote homology detection methods to build 3D models, predict ligand binding sites and analyze the effect of amino acid variants (e.g., nonsynonymous SNPs (nsSNPs)) for a user's protein sequence. Users are guided through results by a simple interface at a level of detail they determine. This protocol will guide users from submitting a protein sequence to interpreting the secondary and tertiary structure of their models, their domain composition and model quality. A range of additional available tools is described to find a protein structure in a genome, to submit large number of sequences at once and to automatically run weekly searches for proteins that are difficult to model. The server is available at http://www.sbg.bio.ic.ac.uk/phyre2. A typical structure prediction will be returned between 30 min and 2 h after submission

Infraestructura tecnológica de servicios semánticos para la Web Semántica

This project aims at creating a network of distributed interoperable semantic services for building more complex ones. These services will be available in semantic Web service libraries, so that they can be invoked by other systems (e.g., semantic portals, software agents, etc.). Thus, to accomplish this objective, the project proposes: a) To create specific technology for developing and composing Semantic Web Services. b) To migrate the WebODE ontology development workbench to this new distributed interoperable semantic service architecture. c) To develop new semantic services (ontology learning, ontology mappings, incremental ontology evaluation, and ontology evolution). d) To develop technological support that eases semantic portal interoperability, using Web services and Semantic Web Services. The project results will be open source, so as to improve their technological transfer. The quality of these results is ensured by a benchmarking process. Keywords: Ontologies and Semantic We

Data-Driven Understanding of Smart Service Systems Through Text Mining

Smart service systems are everywhere, in homes and in the transportation, energy, and healthcare sectors. However, such systems have yet to be fully understood in the literature. Given the widespread applications of and research on smart service systems, we used text mining to develop a unified understanding of such systems in a data-driven way. Specifically, we used a combination of metrics and machine learning algorithms to preprocess and analyze text data related to smart service systems, including text from the scientific literature and news articles. By analyzing 5,378 scientific articles and 1,234 news articles, we identify important keywords, 16 research topics, 4 technology factors, and 13 application areas. We define ???smart service system??? based on the analytics results. Furthermore, we discuss the theoretical and methodological implications of our work, such as the 5Cs (connection, collection, computation, and communications for co-creation) of smart service systems and the text mining approach to understand service research topics. We believe this work, which aims to establish common ground for understanding these systems across multiple disciplinary perspectives, will encourage further research and development of modern service systems

Tetrahydropyrazolo[1,5-a]Pyrimidine-3-Carboxamide and N-Benzyl-6′,7′-Dihydrospiro[Piperidine-4,4′-Thieno[3,2-c]Pyran] analogues with bactericidal efficacy against Mycobacterium tuberculosis targeting MmpL3

Mycobacterium tuberculosis is a major human pathogen and the causative agent for the pulmonary disease, tuberculosis (TB). Current treatment programs to combat TB are under threat due to the emergence of multi-drug and extensively-drug resistant TB. As part of our efforts towards the discovery of new anti-tubercular leads, a number of potent tetrahydropyrazolo[1,5-a]pyrimidine-3-ca​rboxamide(THPP) and N-benzyl-6′,7′-dihydrospiro[piperidine-4,​4′-thieno[3,2-c]pyran](Spiro) analogues were recently identified against Mycobacterium tuberculosis and Mycobacterium bovis BCG through a high-throughput whole-cell screening campaign. Herein, we describe the attractive in vitro and in vivo anti-tubercular profiles of both lead series. The generation of M. tuberculosis spontaneous mutants and subsequent whole genome sequencing of several resistant mutants identified single mutations in the essential mmpL3 gene. This ‘genetic phenotype’ was further confirmed by a ‘chemical phenotype’, whereby M. bovis BCG treated with both the THPP and Spiro series resulted in the accumulation of trehalose monomycolate. In vivo efficacy evaluation of two optimized THPP and Spiro leads showed how the compounds were able to reduce >2 logs bacterial cfu counts in the lungs of infected mice

A colorectal cancer susceptibility new variant at 4q26 in the Spanish population identified by genome-wide association analysis

This work was partially supported by the CENIT program from the Centro Tecnológico Industrial (CEN-20091016), grants from the Spanish Institute of Health Carlos III (ADE10/00026, PI09/02444, PI12/00511, Acción Transversal de Cáncer) grants from the Fondo de Investigacion Sanitaria/FEDER (08/1276, 08/0024, PS09/02368, 11/00219, 11/00681), and by COST office through COST action BM1206. SCB is supported by contracts from the Fondo de Investigación Sanitaria (CP 03-0070). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Centro Tecnológico IndustrialInstituto de Salud Carlos IIIFondo de Investigación Sanitaria / FEDE

HLA-DRB1 association with Henoch-Schonlein purpura

Objective: Henoch-Schönlein purpura (HSP) is the most common vasculitis in children but it is not exceptional in adults. Increased familial occurrence supports a genetic predisposition for HSP. In this context, an association with the human leukocyte antigen-HLA-DRB1*01 phenotype has been suggested in Caucasian individuals with HSP. However, data on the potential association of HSP with HLA-DRB1*01 were based on small case series. To further investigate this issue, we performed HLA-DRB1 genotyping of the largest series of HSP patients ever assessed for genetic studies in Caucasians. Methods: 342 Spanish patients diagnosed with HSP fulfilling the American College of Rheumatology and the Michel et al classification criteria, and 303 sex and ethnically matched controls were assessed. HLA-DRB1 alleles were determined using a PCR-Sequence-Specific-Oligonucleotide Probe (PCR-SSOP) method. Results: A statistically significant increase of HLA-DRB1*01 in HSP patients when compared with controls was found (43% vs 7%, respectively; p<0.001; odds ratio-OR=2.03 [1.43-2.87]). It was due to the increased frequency of HLA-DRB1*0103 phenotype in HSP (14% vs 2%; p<0.001; OR=8.27 [3.46-23.9]). These results remained statistically significant after adjusting for Bonferroni correction. In contrast, a statistically significant decreased frequency of the HLA-DRB1*0301 phenotype was observed in patients compared to controls (5.6% vs 18.1%, respectively; p<0.001, OR=0.26 [0.14-0.47]), even after adjustment for Bonferroni correction. No HLA-DRB1 association with specific features of the disease was found. Conclusion: Our study confirms an association of HSP with HLA-DRB1*01 in Caucasians. Also, a protective effect against the development of HSP appears to exist in Caucasians carrying the HLA-DRB1*03 phenotype