Allele variants in functional MicroRNA target sites of the neurotrophin-3 receptor gene (NTRK3) as susceptibility factors for anxiety disorders

Genetic and functional data indicate that variation in the expression of the neurotrophin-3 receptor gene (NTRK3) may have an impact on neuronal plasticity, suggesting a role for NTRK3 in the pathophysiology of anxiety disorders. MicroRNA (miRNA) posttranscriptional gene regulators act by base-pairing to specific sequence sites, usually at the 3'UTR of the target mRNA. Variants at these sites might result in gene expression changes contributing to disease susceptibility. We investigated genetic variation in two different isoforms of NTRK3 as candidate susceptibility factors for anxiety by resequencing their 3'UTRs in patients with panic disorder (PD), obsessive-compulsive disorder (OCD), and in controls. We have found the C allele of rs28521337, located in a functional target site for miR-485-3p in the truncated isoform of NTRK3, to be significantly associated with the hoarding phenotype of OCD. We have also identified two new rare variants in the 3'UTR of NTRK3, ss102661458 and ss102661460, each present only in one chromosome of a patient with PD. The ss102661458 variant is located in a functional target site for miR-765, and the ss102661460 in functional target sites for two miRNAs, miR-509 and miR-128, the latter being a brain-enriched miRNA involved in neuronal differentiation and synaptic processing. Interestingly, these two variants significantly alter the miRNA-mediated regulation of NTRK3, resulting in recovery of gene expression. These data implicate miRNAs as key posttranscriptional regulators of NTRK3 and provide a framework for allele-specific miRNA regulation of NTRK3 in anxiety disorders.

Decay of linkage disequilibrium within genes across HGDP-CEPH human samples: most population isolates do not show increased LD

Background: It is well known that the pattern of linkage disequilibrium varies between human populations, with remarkable geographical stratification. Indirect association studies routinely exploit linkage disequilibrium around genes, particularly in isolated populations where it is assumed to be higher. Here, we explore both the amount and the decay of linkage disequilibrium with physical distance along 211 gene regions, most of them related to complex diseases, across 39 HGDP-CEPH population samples, focusing particularly on the populations defined as isolates. Within each gene region and population we use r2 between all possible single nucleotide polymorphism (SNP) pairs as a measure of linkage disequilibrium and focus on the proportion of SNP pairs with r2 greater than 0.8.Results: Although the average r2 was found to be significantly different both between and within continental regions, a much higher proportion of r2 variance could be attributed to differences between continental regions (2.8% vs. 0.5%, respectively). Similarly, while the proportion of SNP pairs with r2 > 0.8 was significantly different across continents for all distance classes, it was generally much more homogenous within continents, except in the case of Africa and the Americas. The only isolated populations with consistently higher LD in all distance classes with respect to their continent are the Kalash (Central South Asia) and the Surui (America). Moreover, isolated populations showed only slightly higher proportions of SNP pairs with r2 > 0.8 per gene region than non-isolated populations in the same continent. Thus, the number of SNPs in isolated populations that need to be genotyped may be only slightly less than in non-isolates. Conclusion: The "isolated population" label by itself does not guarantee a greater genotyping efficiency in association studies, and properties other than increased linkage disequilibrium may make these populations interesting in genetic epidemiology.

Genetic and genomic analysis modeling of germline c-MYC overexpression and cancer susceptibility

Background: Germline genetic variation is associated with the differential expression of many human genes. The phenotypic effects of this type of variation may be important when considering susceptibility to common genetic diseases. Three regions at 8q24 have recently been identified to independently confer risk of prostate cancer. Variation at 8q24 has also recently been associated with risk of breast and colorectal cancer. However, none of the risk variants map at or relatively close to known genes, with c-MYC mapping a few hundred kilobases distally. Results: This study identifies cis-regulators of germline c-MYC expression in immortalized lymphocytes of HapMap individuals. Quantitative analysis of c-MYC expression in normal prostate tissues suggests an association between overexpression and variants in Region 1 of prostate cancer risk. Somatic c-MYC overexpression correlates with prostate cancer progression and more aggressive tumor forms, which was also a pathological variable associated with Region 1. Expression profiling analysis and modeling of transcriptional regulatory networks predicts a functional association between MYC and the prostate tumor suppressor KLF6. Analysis of MYC/Myc-driven cell transformation and tumorigenesis substantiates a model in which MYC overexpression promotes transformation by down-regulating KLF6. In this model, a feedback loop through E-cadherin down-regulation causes further transactivation of c-MYC.Conclusion: This study proposes that variation at putative 8q24 cis-regulator(s) of transcription can significantly alter germline c-MYC expression levels and, thus, contribute to prostate cancer susceptibility by down-regulating the prostate tumor suppressor KLF6 gene.

OSIRISv1.2: a named entity recognition system for sequence variants of genes in biomedical literature

Background: Single Nucleotide Polymorphisms, among other type of sequence variants, constitute key elements in genetic epidemiology and pharmacogenomics. While sequence data about genetic variation is found at databases such as dbSNP, clues about the functional and phenotypic consequences of the variations are generally found in biomedical literature. The identification of the relevant documents and the extraction of the information from them are hampered by the large size of literature databases and the lack of widely accepted standard notation for biomedical entities. Thus, automatic systems for the identification of citations of allelic variants of genes in biomedical texts are required. Results: Our group has previously reported the development of OSIRIS, a system aimed at the retrieval of literature about allelic variants of genes http://ibi.imim.es/osirisform.html. Here we describe the development of a new version of OSIRIS (OSIRISv1.2, http://ibi.imim.es/OSIRISv1.2.html webcite) which incorporates a new entity recognition module and is built on top of a local mirror of the MEDLINE collection and HgenetInfoDB: a database that collects data on human gene sequence variations. The new entity recognition module is based on a pattern-based search algorithm for the identification of variation terms in the texts and their mapping to dbSNP identifiers. The performance of OSIRISv1.2 was evaluated on a manually annotated corpus, resulting in 99% precision, 82% recall, and an F-score of 0.89. As an example, the application of the system for collecting literature citations for the allelic variants of genes related to the diseases intracranial aneurysm and breast cancer is presented. Conclusion: OSIRISv1.2 can be used to link literature references to dbSNP database entries with high accuracy, and therefore is suitable for collecting current knowledge on gene sequence variations and supporting the functional annotation of variation databases. The application of OSIRISv1.2 in combination with controlled vocabularies like MeSH provides a way to identify associations of biomedical interest, such as those that relate SNPs with diseases.

Contrasting the form and use of reformulation markers

This paper deals with the form and use of reformulation markers in research papers written in English, Spanish and Catalan. Considering the form and frequency of themarkers, English papers tends to prefer simple fixed markers and includes less reformulators than Spanish and Catalan. On the contrary, formal Catalan and Spanish papers include more markers, some of which are complex and allow for some structural variability. As for use, reformulation markers establish dynamic relationships between portions of discourse which can be identified in our corpus with expansion, reduction, and permutation. The analysis of the corpus shows that English authors usually reformulate to add more information to the concept (expansion), whereas Catalan and Spanish authors reduce the contents or the implicatures of the previous formulation more frequently than English.

Definitional verbal patterns for semantic relation extraction

In this paper we present a description of the role of definitional verbal patterns for the extraction of semantic relations. Several studies show that semantic relations can be extracted from analytic definitions contained in machine-readable dictionaries (MRDs). In addition, definitions found in specialised texts are a good starting point to search for different types of definitions where other semantic relations occur. The extraction of definitional knowledge from specialised corpora represents another interesting approach for the extraction of semantic relations. Here, we present a descriptive analysis of definitional verbal patterns in Spanish and the first steps towards the development of a system for the automatic extraction of definitional knowledge.

Del discurso a la lexicografía: propuesta de aplicación para los conectores reformulativos

This paper aims at defending the necessity of creating applicationsfrom studies on discourse, so that applied linguistics becomes auseful tool for the society. This work explains briefly what reformulation connectors are and it shows the electronic prototype (than can be consulted by internet) of a tool designed to make the work of lexicographerseasy concerning the entrance of connectors in the dictionaries (ALCOR), by making emphasis on the theoretical base on which it is sustained and on the decisions of application that have been taken into account.

El corpus tècnic del IULA: corpus textual especializado plurilingüe

Corpus constituido desde 1993 hasta la actualidad en el marco del proyecto Corpus del Institut Universitari de Lingüística Aplicada (IULA) de la Universidad Pompeu Fabra. Este proyecto recopila textos escritos en cinco lenguas diferentes (catalán, castellano, inglés, francés y alemán) de las áreas de especialidad de la economía, el derecho,el medio ambiente, la medicina y la informática.

Extracción de contextos definitorios hacia la elaboración en corpus especializados: de una herramienta de ayuda terminográfica

Uno de los objetivos principales del trabajo terminográfico es la identificación de conocimientosobre los términos que aparecenen textos especializados. Para confeccionar diccionarios, glosarios u ontologías, los terminógrafos suelen buscar definiciones sobre los términos que pretenden definir. La búsqueda de definiciones se puede hacer apartir de corpus especializados, donde normalmente aparecen en contextos definitorios, es decir, en fragmentos de texto donde un autor explícitamente define el término en cuestión. Hoy en día hay un interés creciente por automatizar este proceso, basado enla búsqueda de patrones definitorios sobre corpus especializados anotados morfosintácticamente. En este artículo presentamos una investigación centrada en la extracción automática de contextos definitorios. Presentamos una metodología que incluye tres procesos automáticos diferentes: la extracción de ocurrencias de patrones definitorios, el filtradode contextos no relevantes, y la identificación de elementos constitutivos, es decir, términos, definiciones y patrones pragmáticos.

Camiños denominativos cara a un mesmo concepto

Neste artigo presentamos unha revisión teórica sobre o concepto especializado e a relación que mantén coa variación. Nós defendemos que existe un grao de motivación importante na denominación terminolóxica e que, a través dela, se fan visibles uns trazos semánticos determinados, achegándonos así unha visión particular do concepto. Por último facemos unha proposta de análise da variación terminolóxica consistnete en recompilar as diferentes variantes e analizar o contenido semántico expresado na denominación. Os exemplos foron tirados dun corpus de textos bilingüe francés-galego sobre o marisqueo.

Implantación del plan de refuerzo del inglés en la Escuela deIngeniería de Telecomunicación. Universidad Pompeu Fabra

Teniendo en cuenta la importancia del uso del inglés en la cotidianeidad del desempeño profesional del Ingeniero en Telecomunicaciones se ha diseñado un proyecto de innovación docente fundamentado en la inmersión de los estudiantes en esta lengua.

A new hybrid summarizer based on vector Space model, statistical physics and linguistics

In this article we present a hybrid approach for automatic summarization of Spanish medical texts. There are a lot of systems for automatic summarization using statistics or linguistics, but only a few of them combining both techniques. Our idea is that to reach a good summary we need to use linguistic aspects of texts, but as well we should benefit of the advantages of statistical techniques. We have integrated the Cortex (Vector Space Model) and Enertex (statistical physics) systems coupled with the Yate term extractor, and the Disicosum system (linguistics). We have compared these systems and afterwards we have integrated them in a hybrid approach. Finally, we have applied this hybrid system over a corpora of medical articles and we have evaluated their performances obtaining good results.

Sobre el discurs normatiu de l'Institut d'Estudis Catalans

L’objectiu d’aquest text és analitzar la il•locutivitat del discurs normatiu de l’Institut d’Estudis Catalans (IEC): és a dir, fins a quin punt la comunitat lingüística catalana rep clarament la normativa de l’IEC i què condiciona aquest grau de claredat. Per fer aquesta anàlisi, argumentem, en primer lloc, quina mena d’emissor és l’IEC i fins a quin punt l’Acadèmia Valenciana de la Llengua (AVL) li disputa les seves atribucions discursives; en segon lloc, fins a quin punt l’IEC emet missatges coherents sobre una mateixa qüestió; i, en tercer lloc, quin tipus de receptor és el destinatari dels missatges de l’IEC. Un cop presentats aquests elements del discurs normatiu de l’IEC, ens plantegem fins a quin punt aquesta comunicació és clara en la situació comunicativa que es dóna quan un catalanoparlant consulta una obra normativa. Aquesta anàlisi s’exemplifica en una frase creada ad hoc amb unes quantes formes la correcció de les quals ha estat tradicionalment discutida.

El Corpus de l'IULA: etiquetaris

El projecte central que es duu a terme a l'Institut Universitari de Lingüística Aplicada (IULA) de la Universitat Pompeu Fabra és el corpus de Llenguatges especialitzats. En el marc d'aquest projecte —que implica cinc dominis d'especialitat (dret, economia, informàtica, medi ambient i medicina) i cinc llengües (català, castellà, francès, anglès i alemany)— s'han desenvolupat dos etiquetaris per a la llengua catalana i castellana. Amb el desenvolupament d'aquests etiquetaris es pretén facilitar l'etapa del processament lingüístic del corpus. En aquest paper es discuteixen, d'una banda, alguns aspectes teòrics relatius a la construcció d'etiquetaris i, de l'altra, es presenten els dos etiquetaris que s'han elaborat a l'IULA.

Descripció quantitativa dels neologismes documentats durant l'any 1995 a la premsa en català

Descripció dels neologismes de l'Observatori de Neologia documentats a la premsa en català (Avui, Punt Diari, El Temps) de l'any 1995, a partir del recurs de creació que els ha generat: processos formals (derivació, composició, sintagmació, conversió sintàctica, truncació, etc.), processos semàntics i manlleus.