Adaptación del Inventario de la Triada Cognitiva Infantil en población española

Depression is one of the mental disorders that concern worldwide. One theory that has attracted more researches is the Beck´s cognitive theory of depression. The Cognitive Triad Inventory (CTI) has been developed to evaluate the different components of the cognitive triad, although most studies had been developed in adult and adolescent population. The aim of this work is to show evidence of factorial validity of the reduced version of the CTI, and the study of the psychometric properties of the inventory in children. In the sample of 3292 children with age between 8 and 13 (M=9.86; SD =1.24), the results showed a better factorial fit with a bifactorial model (positive triad and negative triad). The reliability of the dimensions is good (α=.88 and .92 respectively) and convergent validity evidence is adequate. The inventory was evaluated from the Item Response Theory framework, showing correct properties. Finally the norms of the questionnaire were made addressing the gender differences that were found previously.La depresión es uno de los trastornos mentales que más preocupan a nivel mundial. Una de las teorías que más investigación ha suscitado es la teoría cognitiva de la depresión de Beck. El Inventario de Tríada Cognitiva (CTI) se ha elaborado para  evaluar los diferentes componentes de la tríada cognitiva, si bien la mayoría de sus estudios se han desarrollado en población adulta y adolescente. El objetivo de este trabajo es mostrar evidencias de validez factorial de la versión reducida del CTI, así como el estudio de las propiedades psicométricas del cuestionario en población infantil. En una muestra de 3.292 niños de edades entre los 8 y los 13 años (M=9.8 y D.T.=1.24), los resultados mostraron que el mejor ajuste factorial se obtiene con una estructura bifactorial (tríada positiva y tríada negativa). La fiabilidad de las diferentes dimensiones es buena (α=.88 y .92 respectivamente). Las evidencias de validez convergente son adecuadas. El cuestionario fue evaluado también desde la perspectiva de la Teoría de la Respuesta a los Ítems mostrando unas propiedades correctas. Finalmente se realizó la baremación del cuestionario atendiendo a las diferencias por género encontradas previamente

Targeting Protein Kinase C in Glioblastoma Treatment

Glioblastoma (GBM) is the most frequent and aggressive primary brain tumor and is associated with a poor prognosis. Despite the use of combined treatment approaches, recurrence is almost inevitable and survival longer than 14 or 15 months after diagnosis is low. It is therefore necessary to identify new therapeutic targets to fight GBM progression and recurrence. Some publications have pointed out the role of glioma stem cells (GSCs) as the origin of GBM. These cells, with characteristics of neural stem cells (NSC) present in physiological neurogenic niches, have been proposed as being responsible for the high resistance of GBM to current treatments such as temozolomide (TMZ). The protein Kinase C (PKC) family members play an essential role in transducing signals related with cell cycle entrance, differentiation and apoptosis in NSC and participate in distinct signaling cascades that determine NSC and GSC dynamics. Thus, PKC could be a suitable druggable target to treat recurrent GBM. Clinical trials have tested the efficacy of PKC beta inhibitors, and preclinical studies have focused on other PKC isozymes. Here, we discuss the idea that other PKC isozymes may also be involved in GBM progression and that the development of a new generation of effective drugs should consider the balance between the activation of different PKC subtypes

Clustered Gene Expression Changes Flank Targeted Gene Loci in Knockout Mice

Gene expression profiling using microarrays is a powerful technology widely used to study regulatory networks. Profiling of mRNA levels in mutant organisms has the potential to identify genes regulated by the mutated protein.Using tissues from multiple lines of knockout mice we have examined genome-wide changes in gene expression. We report that a significant proportion of changed genes were found near the targeted gene.The apparent clustering of these genes was explained by the presence of flanking DNA from the parental ES cell. We provide recommendations for the analysis and reporting of microarray data from knockout mice

International consensus recommendations on the diagnostic work-up for malformations of cortical development

Malformations of cortical development (MCDs) are neurodevelopmental disorders that result from abnormal development of the cerebral cortex in utero. MCDs place a substantial burden on affected individuals, their families and societies worldwide, as these individuals can experience lifelong drug-resistant epilepsy, cerebral palsy, feeding difficulties, intellectual disability and other neurological and behavioural anomalies. The diagnostic pathway for MCDs is complex owing to wide variations in presentation and aetiology, thereby hampering timely and adequate management. In this article, the international MCD network Neuro-MIG provides consensus recommendations to aid both expert and non-expert clinicians in the diagnostic work-up of MCDs with the aim of improving patient management worldwide. We reviewed the literature on clinical presentation, aetiology and diagnostic approaches for the main MCD subtypes and collected data on current practices and recommendations from clinicians and diagnostic laboratories within Neuro-MIG. We reached consensus by 42 professionals from 20 countries, using expert discussions and a Delphi consensus process. We present a diagnostic workflow that can be applied to any individual with MCD and a comprehensive list of MCD-related genes with their associated phenotypes. The workflow is designed to maximize the diagnostic yield and increase the number of patients receiving personalized care and counselling on prognosis and recurrence risk

The Epigenetics of Glioma Stem Cells: A Brief Overview

Glioma stem cells (GSCs) are crucial in the formation, perpetuation and recurrence of glioblastomas (GBs) due to their self-renewal and proliferation properties. Although GSCs share cellular and molecular characteristics with neural stem cells (NSCs), GSCs show unique transcriptional and epigenetic features that may explain their relevant role in GB and may constitute druggable targets for novel therapeutic approaches. In this review, we will summarize the most important findings in GSCs concerning epigenetic-dependent mechanisms.LV is supported by the Plan Propio INiBICA (Grant L19-07IN-CO07) and by the Programa Estatal de Generación de Conocimiento y Fortalecimiento del Sistema Español de I+D+i, financed by the Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional 2014-2020 (Grants CP15/00180 and PI16/00722). LV is the recipient of a Miguel Servet I contract (CP15/00180) financed by the Instituto de Salud Carlos III and Fondo Social Europeo 2014-2020, Programa Estatal de Promoción del Talento y su empleabilidad en I+D+i.Ye

A Glimpse of Molecular Biomarkers in Huntington’s Disease

Huntington’s disease (HD) is a devastating neurodegenerative disorder that is caused by an abnormal expansion of CAG repeats in the Huntingtin (HTT) gene. Although the main symptomatology is explained by alterations at the level of the central nervous system, predominantly affecting the basal ganglia, a peripheral component of the disease is being increasingly acknowledged. Therefore, the manifestation of the disease is complex and variable among CAG expansion carriers, introducing uncertainty in the appearance of specific signs, age of onset and severity of disease. The monogenic nature of the disorder allows a precise diagnosis, but the use of biomarkers with prognostic value is still needed to achieve clinical management of the patients in an individual manner. In addition, we need tools to evaluate the patient’s response to potential therapeutic approaches. In this review, we provide a succinct summary of the most interesting molecular biomarkers that have been assessed in patients, mostly obtained from body fluids such as cerebrospinal fluid, peripheral blood and saliva

Ablation of CBP in forebrain principal neurons causes modest memory and transcriptional defects and a dramatic reduction of histone acetylation but does not affect cell viability

Rubinstein-Taybi syndrome (RSTS) is an inheritable disease associated with mutations in the gene encoding the CREB (cAMP response element-binding protein)-binding protein (CBP) and characterized by growth impairment, learning disabilities, and distinctive facial and skeletal features. Studies in mouse models for RSTS first suggested a direct role for CBP and histone acetylation in cognition and memory. Here, we took advantage of the genetic tools for generating mice in which the CBP gene is specifically deleted in postmitotic principal neurons of the forebrain to investigate the consequences of the loss of CBP in the adult brain. In contrast to the conventional CBP knock-out mice, which exhibit very early embryonic lethality, postnatal forebrain-restricted CBP mutants were viable and displayed no overt abnormalities.Weidentified the dimer of histones H2A and H2B as the preferred substrate of the histone acetyltransferase domain of CBP. Surprisingly, the loss of CBP and subsequent histone hypoacetylation had a very modest impact in the expression of a number of immediate early genes and did not affect neuronal viability. In addition, the behavioral characterization of these mice dissociated embryonic and postnatal deficits caused by impaired CBP function, narrowed down the anatomical substrate of specific behavioral defects, and confirmed the special sensitivity of object recognition memory to CBP deficiency. Overall, our study provides novel insights into RSTS etiology and clarifies some of the standing questions concerning the role of CBP and histone acetylation in activity-driven gene expression, memory formation, and neurodegeneration. Copyright © 2011 the authors.Research at the laboratory of A.B. is supported by Spanish Ministry of Science and Innovation Grants BFU2008-00611, CSD2007-00023, and SAF2008-03194-E (part of the coordinated ERA-Net NEURON Project Epitherapy) and grants from Fundación Ramón Areces and Fundació La Marató de TV3 063510. L.M.V. has a Ramón y Cajal contract given by the Spanish Ministry of Science and Innovation.Peer Reviewe

Distribution of significant genes between all the chromosomes.

<p>χ² tests were performed in the available mutants under the null hypothesis of random distribution: Random, equal proportion; Norm.1, proportion normalized by chromosome length; Norm.2, normalized by number of genes in each chromosome (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001303#s4" target="_blank">Materials and Methods</a>): *, p<0.1; **, p<0.05; ***, p<0.01; ****, p<0.001. Percentages are the contribution of the chromosome for each ablated gene to the deviation from each random distribution and were calculated as proportion of the χ² values. If a chromosome other than that encoding the knock-out gene had more contribution is stated in “Other chrom”. Total genes are the number of the retrieved significant genes.</p