Expressió del receptor domini discoidina 1 (DDR1) en cervell huma. Relació amb l'esquizofrènia

L'esquizofrènia és una de les psicosis més comunes que té una prevalença d'un 1% en la població mundial i una etiologia desconeguda. Una de les hipòtesis etiopatològiques més recolzades per l'esquizofrènia és la teoria del neurodesenvolupament la qual postula que l'origen de la esquizofrènia tindria lloc per alteracions de la neurogènesi i gliogènesi en les etapes del desenvolupament perinatal. Nombrosos estudis han descrit diverses alteracions de la mielina (substància blanca del cervell) en pacients esquizofrènics. La mielinització dels axons és important per una correcta transmissió del senyal entre neurones. Les cèl·lules responsables de sintetitzar mielina per embolcallar el axons en el cervell són els oligodendròcits. En humans els majors pics del procés de mielinització ocorren en la etapa perinatal, infantesa i adolescència. En aquesta última etapa és on es manifesten majoritàriament els primers símptomes de l'esquizofrènia.Diversos estudis de lligament apunten a que a la regió cromosòmica 6p hi podria haver un gen o gens de susceptibilitat per l'esquizofrènia. El nostre grup va escollir un gen d'aquesta regió, el gen que codifica pel Receptor Domini Discoidina 1 (DDR1), com a candidat per l'esquizofrènia. Se sap que DDR1 és un receptor tirosina quinasa que s'expressa de forma molt important en zones proliferatives durant el neurodesenvolupament del cervell de rata i ratolí i també s'ha vist que s'expressa en cervell humà. DDR1 té com lligant el col·lagen, el qual promou la diferenciació i proliferació de les cèl·lules neuroepitelials en rates. El nostre grup ha observat una important expressió de DDR1 en la substància blanca i en concret en els oligodendròcits durant el desenvolupament pre i postnatal en ratolins. A demés l'expressió d'aquest receptor segueix un patró espacio-temporal al procés de mielinització. En la present tesi doctoral hem estudiat per primera vegada en detall el patró d'expressió gènica i proteïca del receptor DDR1 en cervell humà mitjançant tècniques específiques d'hibridació in situ, immunohistoquímica i de quantificació d'RNAm. Hem trobat que existeix una associació positiva tan a nivell gènic com haplotípic de DDR1 amb l'esquizofrènia mitjançant un estudi d'anàlisi de variants tipus SNPs en una mostra de casos i control. També hem descrit per primera vegada que DDR1 és una proteïna de la mielina en cervell humà i que entre les 5 diferents isoformes que es coneixen només les isoformes DDR1c i DDR1a es relacionen amb la mielina. D'aquesta tesi es deriven les següents aportacions científiques: - Roig B, Virgos C, Franco N, Martorell L, Valero J, Costas J, Carracedo A, Labad A, Vilella E. The discoidin domain receptor 1 as a novel susceptibility gene for schizophrenia. Molecular Psychiatry. 2007. doi: 10.1038/sj.mp.4001995. IF: 11.8- Roig B, Franco-Pons N, Martorell L, Tomàs J, Costas J, Vogel WF, Vilella E. Identification of the tyrosine kinase receptor discoidin domain 1 (DDR1) as a novel myelin protein. Sotmés a revisió a la revista Glia. IF: 4.1- Roig B, Franco-Pons N, Martorell L, Vilella E. Quantitative analysis of DDR1 mRNA expression in normal and schizophrenic brain. Manuscrit en preparació.Schizophrenia is one of the most common psychoses in the world today. It has a prevalence of 1% in the population and is of unknown etiology. One of the most widely accepted etiopathogenic hypotheses for schizophrenia is neurodevelopmental theory, which postulates that schizophrenia originates from a variety of neurogenetic and gliogenetic disorders during perinatal development. Many studies have reported that schizophrenic patients have alterations in their myelin (white matter of the brain). Axons must be myelinated if signals are to be properly transmitted between neurons. The cells that form the myelin sheaths of the axons in the CNS are the oligodendrocytes.In humans, the myelination process peaks in the perinatal, childhood and adolescence stages. It is during this last stage that the symptoms of schizophrenia become manifest. Several linkage studies indicate that the 6p chromosomal region may contain one or more susceptibility genes for schizophrenia. Our group chose a gene in this region, the gene encoding the discoidin domain receptor 1 (DDR1), as a candidate gene for schizophrenia.DDR1 is known to be a receptor tyrosine kinase which is highly expressed in proliferative areas during murine brain development, and has also been shown to be expressed in human brain. The DDR1 ligand is collagen, which promotes the proliferation and differentiation of the neurophitelial cells in rats. Our group has observed that DDR1 is significantly expressed in the white matter and particularly in oligodendrocytes during pre- and postnatal development in mice. Furthermore, the expression of this receptor follows a spatial-temporal pattern similar to the process of myelination.In this doctoral thesis we have made the first detailed study of the pattern of gene and protein expression of DDR1 in human brain, using specific techniques such as in situ hybridization, immunohistochemistry and quantification of RNAm. We found a positive association of DDR1 with schizophrenia in a case-control association study using markers of the SNP (single nucleotide polymorphism) type.We have also reported for the first time that DDR1 is a myelin protein in the human brain and that of the five different isoforms that are known only isoforms DDR1c and DDR1a are related to the myelin.The following scientific articles have been written as a result of this doctoral thesis:- Roig B, Virgos C, Franco N, Martorell L, Valero J, Costas J, Carracedo A, Labad A, Vilella E. The discoidin domain receptor 1 as a novel susceptibility gene for schizophrenia. Molecular Psychiatry. 2007. doi: 10.1038/sj.mp.4001995. IF: 11.8- Roig B, Franco-Pons N, Martorell L, Tomàs J, Costas J, Vogel WF, Vilella E. Identification of the tyrosine kinase receptor discoidin domain 1 (DDR1) as a novel myelin protein. Submitted to Glia. IF: 4.1- Roig B, Franco-Pons N, Martorell L, Vilella E. Quantitative analysis of DDR1 mRNA expression in normal and schizophrenic brain. Manuscript in preparation

Plan de comunicación: el raconet de Chelo

Treball Final de Grau en Publicitat i Relacions Públiques. Codi: PU0932. Curs acadèmic: 2020/2021En el siguiente trabajo se va a desarrollar un plan de comunicación para la solución de algunos problemas que se plantean de la empresa El Raconet de Chelo. A través de un análisis del contexto, el entorno y la situación de la empresa, se planteará la estrategia que se debe de llevar a cabo para alcanzar unos objetivos previamente definidos. Primeramente se realiza un profundo y exhaustivo análisis en el que se examinan todos los aspectos relacionados con la empresa, tanto internamente como externa. Para poder realizar esta investigación hemos realizado unos cuestionarios que la gerente de la empresa y su trabajadora, y a su vez se han consultado referencias bibliográficas que nos han ayudado a aclarar algunos conceptos y respaldar nuestros argumentos. Después de dicha investigación, hemos planteado los problemas respecto a la situación en la que se encuentra la empresa, los cuales son: posee unos nuevos servicios no comunicados, ni posicionados y la imagen de la marca no se ajusta a estos. Para poder solucionarlos, se han desarrollado una serie de objetivos que pretenden dar a conocer los servicios que la empresa ofrece, y para ello, se ha planteado una estrategia donde se desarrollan una serie de acciones comunicativas con el fin de comunicar al público estos servicios y posicionarse como empresa que los ofrece. Para concluir, podemos añadir que el plan de comunicación está dirigido únicamente y exclusivamente a la empresa de nuestro caso, y que sin este, no se podrían encontrar soluciones a los diferentes problemas que encontramos.In the following work, a communication plan will be developed to solve some of the problems of the company El Raconet de Chelo. Through an analysis of the context, the environment and the situation of the company, the strategy to be carried out in order to achieve previously defined objectives will be proposed. Firstly, an in-depth and exhaustive analysis is carried out in which all aspects related to the company, both internally and externally, are examined. In order to carry out this research, we carried out questionnaires with the company manager and her employee, and we consulted bibliographical references that helped us to clarify some concepts and support our arguments. After this research, we have raised the problems regarding the situation in which the company finds itself, which are: it has new services that have not been communicated or positioned, and the brand image does not match these. In order to solve them, a series of objectives have been developed with the aim of publicising the services that the company offers, and for this, a strategy has been proposed where a series of communicative actions are developed with the aim of communicating these services to the public and positioning itself as a company that offers them. To conclude, we can add that the communication plan is aimed solely and exclusively at the company in our case, and that without it, it would not be possible to find solutions to the different problems we encountered

SpadaHC: a database to improve the classification of variants in hereditary cancer genes in the Spanish population

Accurate classification of genetic variants is crucial for clinical decision-making in hereditary cancer. In Spain, genetic diagnostic laboratories have traditionally approached this task independently due to the lack of a dedicated resource. Here we present SpadaHC, a web-based database for sharing variants in hereditary cancer genes in the Spanish population. SpadaHC is implemented using a three-tier architecture consisting of a relational database, a web tool and a bioinformatics pipeline. Contributing laboratories can share variant classifications and variants from individuals in Variant Calling Format (VCF) format. The platform supports open and restricted access, flexible dataset submissions, automatic pseudo-anonymization, VCF quality control, variant normalization and liftover between genome builds. Users can flexibly explore and search data, receive automatic discrepancy notifications and access SpadaHC population frequencies based on many criteria. In February 2024, SpadaHC included 18 laboratory members, storing 1.17 million variants from 4306 patients and 16 343 laboratory classifications. In the first analysis of the shared data, we identified 84 genetic variants with clinically relevant discrepancies in their classifications and addressed them through a three-phase resolution strategy. This work highlights the importance of data sharing to promote consistency in variant classifications among laboratories, so patients and family members can benefit from more accurate clinical management.Database URL: https://spadahc.ciberisciii.es/ Overview of SpadaHC and its main views. (A) List of existing variants in SpadaHC (in the image, search for the ATM gene). The 'Expert Cl.' column shows the classification made by a group of experts; the 'Lab Cl.' column shows a summary of the classifications made by the laboratories. (B) Allele frequency of a variant in the SpadaHC population according to clinical suspicion and sex. (C) Classifications provided by the laboratories for a variant. (D) List of patients carrying a variant. (E) Histogram showing the coverage and frequency (allele balance) with which the variant was detected in carrier patients. Alt text: SpadaHC overview; laboratories can share datasets of variant classifications (Excel) and variants from individuals (VCFs + Excel). The datasets undergo quality control, bioinformatics pipeline annotation and database integration before being displayed in SpadaHC. The graphical abstract also shows five views of SpadaHC

Com hem treballat el grup d'ajuda a l'escola infantil 0-3 anys. 'Cómo hemos trabajado el grupo de ayuda en la escuela infantil 0-3 años'

Documento electrónico de 4 páginas en formato PDFSe presenta una experiencia de ayuda psicomotriz aplicada a pequeños de dos y tres años que asisten a las escuelas infantiles municipales de Palma de Mallorca. Se demuestra que es posible realizar un trabajo en esta linea para resolver dificultades de comportamiento o de relación aunque los individuos no tengan bien desarrollado el lenguaje oral. El grupo de ayuda se vio reforzado por la participación de las tutoras correspondientes, los padres y el claustro del centro.BalearesES

Opportunistic genetic screening increases the diagnostic yield and is medically valuable for care of patients and their relatives with hereditary cancer

Background: Multigene panel testing by next-generation sequencing (MGP-NGS) enables the detection of germline pathogenic or likely pathogenic variants (PVs/LPVs) in genes beyond those associated with a certain cancer phenotype. Opportunistic genetic screening based on MGP-NGS in patients with suspicion of hereditary cancer reveals these incidental findings (IFs). Methods: MGP-NGS was performed in patients who fulfilled the clinical criteria to undergo genetic testing according to the Catalan Health Service guidelines. Variants were classified following the American College of Medical Genetics and Genomics-Association for Molecular Pathology guidelines and the Cancer Variant Interpretation Group UK guidelines. Results: IFs were identified in 10 (1.22%) of the 817 patients who underwent MGP-NGS. The mean age at cancer diagnosis was 49.4±9.5 years. Three IFs (30.0%) were detected in PMS2, two (20.0%) in ATM and TP53 and one (10.0%) in MSH6, NTHL1 and VHL. Seven (70.0%) IFs were single-nucleotide substitutions, two (20.0%) were deletions and one (10.0%) was a duplication. Three (30.0) IFs were located in intronic regions, three (30.3%) were nonsense, two (20.0%) were frameshift and two (20.0%) were missense variations. Six (60.0%) IFs were classified as PVs and four (40.0%) as LPVs. Conclusions: Opportunistic genetic screening increased the diagnostic yield by 1.22% in our cohort. Most of the identified IFs were present in clinically actionable genes (n=7; 70.0%), providing these families with an opportunity to join cancer early detection programmes, as well as secondary cancer prevention. IFs might facilitate the diagnosis of asymptomatic individuals and the early management of cancer once it develops

Genetic study of NRXN1β variants in Spanish patients with schizophrenia

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