BRF1 mutations alter RNA polymerase III-dependent transcription and cause neurodevelopmental anomalies.

RNA polymerase III (Pol III) synthesizes tRNAs and other small noncoding RNAs to regulate protein synthesis. Dysregulation of Pol III transcription has been linked to cancer, and germline mutations in genes encoding Pol III subunits or tRNA processing factors cause neurogenetic disorders in humans, such as hypomyelinating leukodystrophies and pontocerebellar hypoplasia. Here we describe an autosomal recessive disorder characterized by cerebellar hypoplasia and intellectual disability, as well as facial dysmorphic features, short stature, microcephaly, and dental anomalies. Whole-exome sequencing revealed biallelic missense alterations of BRF1 in three families. In support of the pathogenic potential of the discovered alleles, suppression or CRISPR-mediated deletion of brf1 in zebrafish embryos recapitulated key neurodevelopmental phenotypes; in vivo complementation showed all four candidate mutations to be pathogenic in an apparent isoform-specific context. BRF1 associates with BDP1 and TBP to form the transcription factor IIIB (TFIIIB), which recruits Pol III to target genes. We show that disease-causing mutations reduce Brf1 occupancy at tRNA target genes in Saccharomyces cerevisiae and impair cell growth. Moreover, BRF1 mutations reduce Pol III-related transcription activity in vitro. Taken together, our data show that BRF1 mutations that reduce protein activity cause neurodevelopmental anomalies, suggesting that BRF1-mediated Pol III transcription is required for normal cerebellar and cognitive development.

Intelligence-led crime scene processing. Part I : Forensic intelligence.

Forensic science is generally defined as the application of science to address questions related to the law. Too often, this view restricts the contribution of science to one single process which eventually aims at bringing individuals to court while minimising risk of miscarriage of justice. In order to go beyond this paradigm, we propose to refocus the attention towards traces themselves, as remnants of a criminal activity, and their information content. We postulate that traces contribute effectively to a wide variety of other informational processes that support decision making inmany situations. In particular, they inform actors of new policing strategies who place the treatment of information and intelligence at the centre of their systems. This contribution of forensic science to these security oriented models is still not well identified and captured. In order to create the best condition for the development of forensic intelligence, we suggest a framework that connects forensic science to intelligence-led policing (part I). Crime scene attendance and processing can be envisaged within this view. This approach gives indications abouthowto structure knowledge used by crime scene examiners in their effective practice (part II).

Implementing statistical learning methods through Bayesian networks. Part 1: a guide to Bayesian parameter estimation using forensic science data

As a thorough aggregation of probability and graph theory, Bayesian networks currently enjoy widespread interest as a means for studying factors that affect the coherent evaluation of scientific evidence in forensic science. Paper I of this series of papers intends to contribute to the discussion of Bayesian networks as a framework that is helpful for both illustrating and implementing statistical procedures that are commonly employed for the study of uncertainties (e.g. the estimation of unknown quantities). While the respective statistical procedures are widely described in literature, the primary aim of this paper is to offer an essentially non-technical introduction on how interested readers may use these analytical approaches - with the help of Bayesian networks - for processing their own forensic science data. Attention is mainly drawn to the structure and underlying rationale of a series of basic and context-independent network fragments that users may incorporate as building blocs while constructing larger inference models. As an example of how this may be done, the proposed concepts will be used in a second paper (Part II) for specifying graphical probability networks whose purpose is to assist forensic scientists in the evaluation of scientific evidence encountered in the context of forensic document examination (i.e. results of the analysis of black toners present on printed or copied documents).

Risc i seguretat en el context educatiu: un debat necessari en el marc d'una educació orientada al desenvolupament de la ciutadania

En aquest article se profunditza en torna a les repercusions dels nous escenaris teòrics relacionats amb el desenvolupament del concepte de risc en la segona modernitat. Les tradicions d'anàlisi de la violència escolar o de la gestió positiva del conflicte, han constituït-del fet encara avui dia constitueixen- referents importants per a l'anàlisi de la seguretat en els centres educatius, però el desenvolupament d'un nou concepte de seguretat humana sorgit a partir dels Programes de les Nacions Unides pel Desenvolupament (PNUD) proporciona un marc de reflexió més ampli. Partint d'aquesta perspectiva, se pretèn operativitzar un model que permeti comprendre com es construeix la percepció de risc en el context escolar.

Age-related changes in the bimanual advantage and in brain oscillatory activity during tapping movements suggest a decline in processing sensory reafference

Deficits in the processing of sensory reafferences have been suggested as accounting for age-related decline in motor coordination. Whether sensory reafferences are accurately processed can be assessed based on the bimanual advantage in tapping: because of tapping with an additional hand increases kinesthetic reafferences, bimanual tapping is characterized by a reduced inter-tap interval variability than unimanual tapping. A suppression of the bimanual advantage would thus indicate a deficit in sensory reafference. We tested whether elderly indeed show a reduced bimanual advantage by measuring unimanual (UM) and bimanual (BM) self-paced tapping performance in groups of young (n = 29) and old (n = 27) healthy adults. Electroencephalogram was recorded to assess the underlying patterns of oscillatory activity, a neurophysiological mechanism advanced to support the integration of sensory reafferences. Behaviorally, there was a significant interaction between the factors tapping condition and age group at the level of the inter-tap interval variability, driven by a lower variability in BM than UM tapping in the young, but not in the elderly group. This result indicates that in self-paced tapping, the bimanual advantage is absent in elderly. Electrophysiological results revealed an interaction between tapping condition and age group on low beta band (14âeuro"20 Hz) activity. Beta activity varied depending on the tapping condition in the elderly but not in the young group. Source estimations localized this effect within left superior parietal and left occipital areas. We interpret our results in terms of engagement of different mechanisms in the elderly depending on the tapping mode: a âeuro~kinestheticâeuro? mechanism for UM and a âeuro~visual imageryâeuro? mechanism for BM tapping movement.

The meaning of marriage for men during the transition to fatherhood : the Swiss context

In Europe, Switzerland presents an unusual pattern of marriage with a very high proportion of couples who begin to cohabit without being married, but with a very low proportion of nonmarital births. A lot of couples marry before the conception of the child or during the pregnancy. In this article we focus on the point of view of men vis-agrave-vis the marriage and its meanings. Qualitative investigations show that men strongly desire marriage for several reasons, from their desire to participate in child rearing to the fear of having their paternity denied by Swiss institutions

The influence of work context on demand for master's studies: a comparative analysisi between Brasil and Spain

The communication presents the results of an investigation of exploratory and comparative character which objective is to analyze the influence of the actual labour situation into the demand of official master studies in the field of education. The study has been developed in two countries with a very different labour situation: Brasil, country of economic expansion and Spain, in recession due to the actual economic crisis. In that sense, the study provides data for deep thinking about the influence of the constriction or expansion of employment on the behaviour and demand of the students who access master studies and on how the previous formative and labour trajectory affects their expectations, demands and future projects. The working methodology is qualitative and the strategy for data collection the “focus group”. As a first approach, two groups of discussion have been formed with master students. A first one with students from Universidad de Barcelona- España and another one with members of Universidade do Vale do Itajaí- Brasil. Then, we constituted a mixed group of discussion in order to analyze differences and similarities.

El professorat d'Educació Física a l'escola multicultural. Percepcions del context i necessitats de formació

El present article se centra en la situació del professorat d'Educació Física i les seves necessitats formatives per actuar adequadament en entorns d'escola multicultural. Amb aquesta finalitat es presenta la importància de l'educació física com a agent socialitzador per a l'alumnat immigrant, les diferents tendències de les investigacions específiques sobre formació del professorat d'Educació Física en temes d'immigració, i les dades obtingudes a través d'una investigació específica realitzada amb una mostra de 230 centres escolars de tot Catalunya. Com a aspectes més remarcables, cal assenyalar que encara que l'educació física i l'esport poden representar un espai de trobada molt valuós per a la interculturalitat, és important no deixar de banda una educació orientada cap a la convivència, i que la formació del professorat sigui coherent amb les necessitats reals que s'observen en i des dels centres escolars.

The influence of work context on demand for master's studies: a comparative analysisi between Brasil and Spain

The communication presents the results of an investigation of exploratory and comparative character which objective is to analyze the influence of the actual labour situation into the demand of official master studies in the field of education. The study has been developed in two countries with a very different labour situation: Brasil, country of economic expansion and Spain, in recession due to the actual economic crisis. In that sense, the study provides data for deep thinking about the influence of the constriction or expansion of employment on the behaviour and demand of the students who access master studies and on how the previous formative and labour trajectory affects their expectations, demands and future projects. The working methodology is qualitative and the strategy for data collection the “focus group”. As a first approach, two groups of discussion have been formed with master students. A first one with students from Universidad de Barcelona- España and another one with members of Universidade do Vale do Itajaí- Brasil. Then, we constituted a mixed group of discussion in order to analyze differences and similarities.