El tractament audiovisual dels fets de la tanca de Ceuta i Melilla : de la visió sensacionalista a la humanitària

L'intent de saltar les tanques de Ceuta i Melilla per part de ciutadans africans, a l'octubre de 2005, va ser cobert per les televisions amb un tractament audiovisual que va sobredimensionar els fets, oferint una imatge gens normalitzada dels immigrants. TV3 va mostrar en conjunt una visió més humanitària, TVE-1 va destacar les actuacions polítiques, Tele 5 va donar prioritat a l'enfrontament polític entre govern i oposició, i Antena 3 va aplicar estratègies informatives adreçades cap al sensacionalisme. Tot i aquestes diferències, hi ha una homogeneïtat de la informació audiovisual, basada en paràmetres comuns. Fins al punt, que hem experimentat un intercanvi de sumaris dels teleinformatius posant l'àudio d'una TV amb les imatges d'una altra i el resultat és un producte sincrònic i totalment vàlid dins dels paràmetres estàndards d'aquest format televisiu

Evidence for the biogenesis of more than 1,000 novel human microRNAs

Background: MicroRNAs (miRNAs) are established regulators of development, cell identity and disease. Although nearly two thousand human miRNA genes are known and new ones are continuously discovered, no attempt has been made to gauge the total miRNA content of the human genome. Results: Employing an innovative computational method on massively pooled small RNA sequencing data, we report 2,469 novel human miRNA candidates of which 1,098 are validated by in-house and published experiments. Almost 300 candidates are robustly expressed in a neuronal cell system and are regulated during differentiation or when biogenesis factors Dicer, Drosha, DGCR8 or Ago2 are silenced. To improve expression profiling, we devised a quantitative miRNA capture system. In a kidney cell system, 400 candidates interact with DGCR8 at transcript positions that suggest miRNA hairpin recognition, and 1,000 of the new miRNA candidates interact with Ago1 or Ago2, indicating that they are directly bound by miRNA effector proteins. From kidney cell CLASH experiments, in which miRNA-target pairs are ligated and sequenced, we observe hundreds of interactions between novel miRNAs and mRNA targets. The novel miRNA candidates are specifically but lowly expressed, raising the possibility that not all may be functional. Interestingly, the majority are evolutionarily young and overrepresented in the human brain. Conclusions: In summary, we present evidence that the complement of human miRNA genes is substantially larger than anticipated, and that more are likely to be discovered in the future as more tissues and experimental conditions are sequenced to greater depth.This project was funded by the Spanish Plan Nacional SAF2008-00357 (NOVADIS); the Generalitat de Catalunya AGAUR 2009 SGR-1502; the Instituto de Salud Carlos III (FIS/FEDER PI11/00733); National Institutes of Health (R00HG004515 to KCC) and the European Commission 7th Framework Program, Projects N. 03790 (SIROCCO), N. 282510 (BLUEPRINT), N. 261123 (GEUVADIS) and N. 262055 (ESGI). MRF is supported by EMBO Long-Term fellowship ALTF 225–2011; EL is supported by the ICGC CLL-Genome project funded by the Spanish Ministry of Economy and Competiveness through the Instituto de Salud Carlos III. AJSH is a Marie Curie postdoctoral fellow supported by the European Commission 7th Framework Program under grant agreement N. 330133. MB-C is a Sara Borrell postdoctoral fellow supported by the Spanish Ministry of Economy and Competiveness. GK was supported by the Wellcome Trust Grant 097383 and by the MRC. EM–H is a PhD student from LaCaix

A Pathogenic Mechanism in Huntington's Disease Involves Small CAG-Repeated RNAs with Neurotoxic Activity

Huntington's disease (HD) is an autosomal dominantly inherited disorder caused by the expansion of CAG repeats in the Huntingtin (HTT) gene. The abnormally extended polyglutamine in the HTT protein encoded by the CAG repeats has toxic effects. Here, we provide evidence to support that the mutant HTT CAG repeats interfere with cell viability at the RNA level. In human neuronal cells, expanded HTT exon-1 mRNA with CAG repeat lengths above the threshold for complete penetrance (40 or greater) induced cell death and increased levels of small CAG-repeated RNAs (sCAGs), of ≈21 nucleotides in a Dicer-dependent manner. The severity of the toxic effect of HTT mRNA and sCAG generation correlated with CAG expansion length. Small RNAs obtained from cells expressing mutant HTT and from HD human brains significantly decreased neuronal viability, in an Ago2-dependent mechanism. In both cases, the use of anti-miRs specific for sCAGs efficiently blocked the toxic effect, supporting a key role of sCAGs in HTT-mediated toxicity. Luciferase-reporter assays showed that expanded HTT silences the expression of CTG-containing genes that are down-regulated in HD. These results suggest a possible link between HD and sCAG expression with an aberrant activation of the siRNA/miRNA gene silencing machinery, which may trigger a detrimental response. The identification of the specific cellular processes affected by sCAGs may provide insights into the pathogenic mechanisms underlying HD, offering opportunities to develop new therapeutic approaches

Galaxy Zoo: the interplay of quenching mechanisms in the group environment

Does the environment of a galaxy directly influence the quenching history of a galaxy? Here, we investigate the detailed morphological structures and star formation histories of a sample of SDSS group galaxies with both classifications from Galaxy Zoo 2 and near ultra-violet (NUV) detections in GALEX. We use the optical and NUV colours to infer the quenching time and rate describing a simple exponentially declining star formation history for each galaxy, along with a control sample of field galaxies. We find that the time since quenching and the rate of quenching do not correlate with the relative velocity of a satellite but are correlated with the group potential. This quenching occurs within an average quenching time-scale of ∼2.5 Gyr from star forming to complete quiescence, during an average infall time (from ∼10 R200 to 0.01 R200) of ∼2.6 Gyr. Our results suggest that the environment does play a direct role in galaxy quenching through quenching mechanisms that are correlated with the group potential, such as harassment, interactions or starvation. Environmental quenching mechanisms that are correlated with satellite velocity, such as ram-pressure stripping, are not the main cause of quenching in the group environment. We find that no single mechanism dominates over another, except in the most extreme environments or masses. Instead, an interplay of mergers, mass and morphological quenching and environment-driven quenching mechanisms dependent on the group potential drive galaxy evolution in groups

Insight into disease processes of fragil X premutation carriers associated pathologies : expression-profile characterization and identification of a novel pathogenic mechanisms

Male premutation carriers (PM) presenting between 55-200 CGG repeats in the Fragile X-associated (FMR1) gene are at risk to develop Fragile X Tremor/Ataxia Syndrome (FXTAS), and females to undergo Premature Ovarian Failure (POF1). These pathologies are caused by toxic gain of function of the premutated FMR1 mRNA. Functional alterations of several gene expression regulators provide a detrimental mechanism underlying FMR1 PM–associated pathologies. In this thesis, we have characterized the transcriptome alterations associated to FMR1 premutation and further characterized the relevance of the biogenesis and activity of a small RNAs formed by repeated CGG (sCGG) in neuronal dysfunction linked to FMR1-PM. In blood of FMR1 premutation carriers (fXPCs) we have detected a strong deregulation of genes enriched in FXTAS-relevant biological pathways. We have also identified a deregulated gene (EAP1) that may underlie POF1 in female fXPCs. In addition, we found increased levels of sCGG in different models of FMR1-PM and further demonstrated the neurotoxic activity of sCGG through a mechanism dependent on RNA induced silencing machinery. We propose that the activity of sCGG may contribute to transcriptome perturbations with downstream pathogenic consequences. Overall, we provide mechanistic insight into the disease process and further suggest targets for FXTAS diagnosis to the myriad of phenotypes associated with FXPC.Homes portadors de la premutació (PM) en el gen associat Fràgil X (FMR1), presenten entre 55-200 repeticions de CGG, estan en risc de desenvolupar el síndrome de tremolor/atàxia associat al X fràgil (FXTAS), i les dones fallida ovàrica precoç (POF1). Aquestes malalties són causades per la funció tòxica de l'ARN missatger. Alteracions funcional de diversos reguladors de l'expressió gènica s'ha proposat com a causa subjacent a aquests trastorns. En aquesta tesi, s'han caracteritzat les alteracions associades al transcriptome de la premutació en l’FMR1 i analitzat la rellevància de la biogènesi i l'activitat d'un petit ARN format per CGG repetits (sCGG) en la disfunció neuronal relacionada amb la PM del FMR1. En sang de portadors de la premutació en l’FMR1 (fXPCs) s'ha detectat una forta desregulació de gens enriquit en vies biològiques rellevants en FXTAS. També hem identificat un gen desregulat (EAP1) que pot ser la base POF1 en dones fXPCs. A més, hem trobat un augment en els nivells de sCGG en diferents models de FMR1-PM i demostrem la seva activitat neurotòxica a través d'un mecanisme dependent en la maquinària de silenciament gènic. Proposem que l'activitat de sCGG pot contribuir a causar pertorbacions en el transcriptoma i desencadenar conseqüències patògenes.En general, oferim un nou enfoc en procés de la malaltia i un diagnòstic més exacte per la gran varietat de fenotips associats amb fXPCs

El tractament audiovisual dels fets de la tanca de Ceuta i Melilla : de la visió sensacionalista a la humanitària

L'intent de saltar les tanques de Ceuta i Melilla per part de ciutadans africans, a l'octubre de 2005, va ser cobert per les televisions amb un tractament audiovisual que va sobredimensionar els fets, oferint una imatge gens normalitzada dels immigrants. TV3 va mostrar en conjunt una visió més humanitària, TVE-1 va destacar les actuacions polítiques, Tele 5 va donar prioritat a l'enfrontament polític entre govern i oposició, i Antena 3 va aplicar estratègies informatives adreçades cap al sensacionalisme. Tot i aquestes diferències, hi ha una homogeneïtat de la informació audiovisual, basada en paràmetres comuns. Fins al punt, que hem experimentat un intercanvi de sumaris dels teleinformatius posant l'àudio d'una TV amb les imatges d'una altra i el resultat és un producte sincrònic i totalment vàlid dins dels paràmetres estàndards d'aquest format televisiu

A pathogenic mechanism in Huntington"s disease involves small CAG-repeated RNAs with neurotoxic activity

Huntington's disease (HD) is an autosomal dominantly inherited disorder caused by the expansion of CAG repeats in the Huntingtin (HTT) gene. The abnormally extended polyglutamine in the HTT protein encoded by the CAG repeats has toxic effects. Here, we provide evidence to support that the mutant HTT CAG repeats interfere with cell viability at the RNA level. In human neuronal cells, expanded HTT exon-1 mRNA with CAG repeat lengths above the threshold for complete penetrance (40 or greater) induced cell death and increased levels of small CAG-repeated RNAs (sCAGs), of ≈21 nucleotides in a Dicer-dependent manner. The severity of the toxic effect of HTT mRNA and sCAG generation correlated with CAG expansion length. Small RNAs obtained from cells expressing mutant HTT and from HD human brains significantly decreased neuronal viability, in an Ago2-dependent mechanism. In both cases, the use of anti-miRs specific for sCAGs efficiently blocked the toxic effect, supporting a key role of sCAGs in HTT-mediated toxicity. Luciferase-reporter assays showed that expanded HTT silences the expression of CTG-containing genes that are down-regulated in HD. These results suggest a possible link between HD and sCAG expression with an aberrant activation of the siRNA/miRNA gene silencing machinery, which may trigger a detrimental response. The identification of the specific cellular processes affected by sCAGs may provide insights into the pathogenic mechanisms underlying HD, offering opportunities to develop new therapeutic approache

A pathogenic mechanism in Huntington"s disease involves small CAG-repeated RNAs with neurotoxic activity

Huntington's disease (HD) is an autosomal dominantly inherited disorder caused by the expansion of CAG repeats in the Huntingtin (HTT) gene. The abnormally extended polyglutamine in the HTT protein encoded by the CAG repeats has toxic effects. Here, we provide evidence to support that the mutant HTT CAG repeats interfere with cell viability at the RNA level. In human neuronal cells, expanded HTT exon-1 mRNA with CAG repeat lengths above the threshold for complete penetrance (40 or greater) induced cell death and increased levels of small CAG-repeated RNAs (sCAGs), of ≈21 nucleotides in a Dicer-dependent manner. The severity of the toxic effect of HTT mRNA and sCAG generation correlated with CAG expansion length. Small RNAs obtained from cells expressing mutant HTT and from HD human brains significantly decreased neuronal viability, in an Ago2-dependent mechanism. In both cases, the use of anti-miRs specific for sCAGs efficiently blocked the toxic effect, supporting a key role of sCAGs in HTT-mediated toxicity. Luciferase-reporter assays showed that expanded HTT silences the expression of CTG-containing genes that are down-regulated in HD. These results suggest a possible link between HD and sCAG expression with an aberrant activation of the siRNA/miRNA gene silencing machinery, which may trigger a detrimental response. The identification of the specific cellular processes affected by sCAGs may provide insights into the pathogenic mechanisms underlying HD, offering opportunities to develop new therapeutic approache