Decoding Agc1 deficiency: bioinformatics approaches to unveil the functional implications of Slc25a12 on the transcriptome and epigenome

In the brain, mutations in SLC25A12 gene encoding AGC1 cause an ultra-rare genetic disease reported as a developmental and epileptic encephalopathy associated with global cerebral hypomyelination. Symptoms of the disease include diffused hypomyelination, arrested psychomotor development, severe hypotonia, seizures and are common to other neurological and developmental disorders. Amongst the biological components believed to be most affected by AGC1 deficiency are oligodendrocytes, glial cells responsible for myelination. Recent studies (Poeta et al, 2022) have also shown how altered levels of transcription factors and epigenetic modifications greatly affect proliferation and differentiation in oligodendrocyte precursor cells (OPCs). In this study we explore the transcriptomic landscape of Agc1 in two different system models: OPCs silenced for Agc1 and iPSCs from human patients differentiated to neural progenitors. Analyses range from differential expression analysis, alternative splicing, master regulator analysis. ATAC-seq results on OPCs were integrated with results from RNA-Seq to assess the activity of a TF based on the accessibility data from its putative targets, which allows to integrate RNA-Seq data to infer their role as either activators or repressors. All the findings for this model were also integrated with early data from iPSCs RNA-seq results, looking for possible commonalities between the two different system models, among which we find a downregulation in genes encoding for SREBP, a transcription factor regulating fatty acids biosynthesis, a key process for myelination which could explain the hypomyelinated state of patients. We also find that in both systems cells tend to form more neurites, likely losing their ability to differentiate, considering their progenitor state. We also report several alterations in the chromatin state of cells lacking Agc1, which confirms the hypothesis for which Agc1 is not a disease restricted only to metabolic alterations in the cells, but there is a profound shift of the regulatory state of these cells.

A interpretação da comunicação publicitária na perspetiva do segmento sénior: contributo para a sua compreensão

O aumento da esperança média de vida e a redução do número de nascimentos, tem conduzido a um aumento significativo da população sénior, e apesar de ser conotado como um fenómeno característico dos países desenvolvidos, esta é uma realidade quase universal, que tem assumido particular incidência na Europa. No entanto, apesar de frequentemente estigmatizada com base em estereótipos negativos, no que diz respeito às suas capacidades físicas e mentais, na atualidade, o perfil dos seniores, sofreu alterações significativas dada a sua disponibilidade de tempo e dinheiro, transformando-o num segmento com um peso significativo no incremento da economia e um target desejável para os media e seus agentes. Deste modo, por via da alteração do paradigma social; envelhecimento da população e a crescente importância deste segmento para o mercado, é pertinente compreender a relação entre o sénior e a comunicação publicitária. Nesse sentido, o objetivo deste paper é proceder a uma revisão narrativa que permita compreender as principais tendências de pesquisa neste campo. Serão assim examinadas as duas abordagens empíricas relativas a esta temática, a primeira centrada na comunicação publicitária dirigida ao sénior e suas caraterísticas e a segunda a comunicação publicitária do ponto de vista do sénior.

Assessment of Young Learners’ English Proficiency in Bilingual Content Instruction CLIL

This applied linguistic study in the field of second language acquisition investigated the assessment practices of class teachers as well as the challenges and visions of language assessment in bilingual content instruction (CLIL) at primary level in Finnish basic education. Furthermore, pupils’ and their parents’ perceptions of language assessment and LangPerform computer simulations as an alternative, modern assessment method in CLIL contexts were examined. The study was conducted for descriptive and developmental purposes in three phases: 1) a CLIL assessment survey; 2) simulation 1; and 3) simulation 2. All phases had a varying number of participants. The population of this mixed methods study were CLIL class teachers, their pupils and the pupils’ parents. The sampling was multi-staged and based on probability and random sampling. The data were triangulated. Altogether 42 CLIL class teachers nationwide, 109 pupils from the 3rd, 4th and 5th grade as well as 99 parents from two research schools in South-Western Finland participated in the CLIL assessment survey followed by an audio-recorded theme interview of volunteers (10 teachers, 20 pupils and 7 parents). The simulation experimentations 1 and 2 produced 146 pupil and 39 parental questionnaires as well as video interviews of volunteered pupils. The data were analysed both quantitatively using percentages and numerical frequencies and qualitatively employing thematic content analysis. Based on the data, language assessment in primary CLIL is not an established practice. It largely appears to be infrequent, incidental, implicit and based on impressions rather than evidence or the curriculum. The most used assessment methods were teacher observation, bilingual tests and dialogic interaction, and the least used were portfolios, simulations and peer assessment. Although language assessment was generally perceived as important by teachers, a fifth of them did not gather assessment information systematically, and 38% scarcely gave linguistic feedback to pupils. Both pupils and parents wished to receive more information on CLIL language issues; 91% of pupils claimed to receive feedback rarely or occasionally, and 63% of them wished to get more information on their linguistic coping in CLIL subjects. Of the parents, 76% wished to receive more information on the English proficiency of their children and their linguistic development. This may be a response to indirect feedback practices identified in this study. There are several challenges related to assessment; the most notable is the lack of a CLIL curriculum, language objectives and common ground principles of assessment. Three diverse approaches to language in CLIL that appear to affect teachers’ views on language assessment were identified: instrumental (language as a tool), dual (language as a tool and object of learning) and eclectic (miscellaneous views, e.g. affective factors prioritised). LangPerform computer simulations seem to be perceived as an appropriate alternative assessment method in CLIL. It is strongly recommended that the fundamentals for assessment (curricula and language objectives) and a mutual assessment scheme should be determined and stakeholders’ knowledge base of CLIL strengthened. The principles of adequate assessment in primary CLIL are identified as well as several appropriate assessment methods suggested.

La conception herméneutique du langage : pour une mise en dialogue des herméneutiques de Gadamer et Ricoeur

L’objet de ce travail de recherche est de mettre en dialogue les œuvres de Hans-Georg Gadamer et de Paul Ricœur afin de mettre au jour ce qui caractérise en propre la conception herméneutique du langage et d’en souligner la pertinence. Notre thèse principale est que, pour ce faire, il est impératif de dépasser les lectures dichotomiques des deux œuvres par une interprétation plus dialectique, puisque seule une telle démarche paraît susceptible de saisir l’étendue, la richesse et l’importance de l’intelligence herméneutique du phénomène langagier. Ainsi, dans ce travail, nous défendrons l’idée que, par-delà leurs différences incontestables, précieuses en elles-mêmes car sans elles il n’est pas de dialogue, les herméneutiques de Gadamer et Ricœur se distinguent par une réflexion philosophique incessante sur notre appartenance fondamentale au langage, qui constitue le cœur de la conception herméneutique du langage. Nous proposerons une confrontation des philosophies de Gadamer et Ricœur s’effectuant principalement autour d’une dialectique entre appartenance et distanciation, dans laquelle des approches plus objectivantes du langage pourront s’articuler à une description de notre expérience vécue. Avant de décrire cette dialectique pour elle-même, il nous est apparu indiqué de tenir compte de l’héritage phénoménologique incontournable à partir duquel Gadamer et Ricœur ont développé leurs approches respectives du langage. Cette base nous permettra de faire ressortir l’existence d’un accord de fond entre les deux herméneutiques sur la reconnaissance de notre irréductible appartenance au langage. Cette thèse n’exclut pas la possibilité, voire la nécessité d’intégrer dialectiquement un moment de distanciation au sein de cette appartenance primordiale. Nous montrerons en effet que c’est en s’appuyant sur cette distanciation que, par un mouvement réflexif, la pensée herméneutique peut revenir sur notre expérience langagière pour la thématiser et l’expliciter. Cette réflexion sur le langage s’effectue à partir de trois principaux modèles : ceux du dialogue, du texte et de la traduction. Nous exposerons comment chacun de ces modèles contribue à une meilleure compréhension de la vie du langage et de notre rapport au sens. Ceci nous conduira à examiner les efforts de Gadamer et Ricœur visant à mettre en lumière la puissance créatrice qui anime le langage, telle qu’elle ressort de leurs nombreux travaux sur la métaphore, le dire poétique et le récit. Nous défendrons alors la thèse qu’une conception originale de l’imagination s’élabore à travers la réflexion herméneutique sur l’innovation sémantique et la métaphoricité essentielle du langage. Cette recherche se terminera par une analyse des conceptions gadamérienne et ricœurienne des rapports entre langage et expérience, ainsi que de la portée ontologique du langage. Il y aura ici lieu d’insister sur la thèse partagée par les deux herméneutes selon laquelle il importe de résister à toute hypostase ou absolutisation du langage et de constamment penser le langage comme offrant une ouverture sur l’être et la possibilité de dire ce qui est.

Acquisition of inflected and uninflected infinitives in child L1 European Portuguese

This study investigates the child (L1) acquisition of inflected and uninflected infinitives in European Portuguese (EP). We test and contrast properties involving two interfaces, focusing on morpho-syntactic and syntax-semantics properties of inflected infinitives, in contrast with uninflected infinitives. We present experimental results from three monolingual EP child groups, between ages 6 and 12 (n=72), compared to EP adults (n=32). Results show that children as young as 6-7 have knowledge of the morpho-syntactic properties of inflected infinitives, although at first glance they show insufficient knowledge of their syntax-semantics interface properties (i.e. non-obligatory control properties), differently from older children, who show evidence of knowledge of both types of properties. We argue that, in general, morpho-syntactic and syntax-semantics interface distinctions are also accessible to 6-7 children, but children may not show the entire range of interpretations possible for adults.

Sexually dimorphic legs in a neotropical harvestman (Arachnida, Opiliones): Ornament or weapon?

The evolution of sexually dimorphic traits has been the focus of much theoretical work, but empirical approaches to this topic have not been equally prolific. Males of the neotropical family Gonyleptidae usually present a strong fourth pair of legs armed with spines, but their functional significance is unknown. We investigated the putative functions of the leg armature in the harvestman Neosadocus maximus. Being a non-visual species. the spines on male legs can only be perceived by females through physical contact. Thus, we could expect females to touch the armature on the legs of their mates if they were to evaluate it. However, we found no support for this hypothesis. We did show that (1) leg armature is used as a weapon in contests between mates and (2) spines and associated sensilla are sexually dimorphic structures involved in ""nipping behavior"", during which a winner emerged in most fights. Finally, we demonstrate that five body structures directly involved in male-male fights show positive allometry in males. presenting slopes higher than 1, whereas the same structures show either no or negative allometry in the case of females. In conclusion, leg armature in male harvestmen is clearly used as a device in intrasexual contests. (C) 2008 Elsevier B.V. All rights reserved.

LA ANSIEDAD Y SU RELACIÓN CON LA EXPRESIÓN ORAL EN EL APRENDIZAJE DE LENGUAS EXTRANJERAS : Una elaboración de revisión sistemática de la literatura

La importancia de la dimensión afectiva que acompaña el proceso de adquisición de lenguas extranjeras es indiscutible. Sin embargo, a pesar de esta realidad, y de la evolución de los enfoques comunicativos como métodos de enseñanza de idiomas, la literatura continúa asegurando la existencia de aprensión lingüística en el aula y su efecto debilitador en el proceso de aprendizaje de una nueva lengua. Este estudio tiene como objetivo examinar cómo el aprendiz experimenta la variable de la ansiedad al expresarse oralmente y en qué medida el profesorado de lenguas extranjeras puede lograr crear condiciones en la clase que reduzcan los niveles de ansiedad. En este trabajo utilizamos la revisión sistemática de literatura como estrategia de investigación, un método que constituye una buena herramienta, permitiéndonos sintetizar coherentemente, de forma rigurosa, los resultados de los estudios empíricos sobre el fenómeno de la ansiedad. Los análisis revelan, en primer lugar, que los síntomas experimentados por aprendices de una nueva lengua suelen manifestarse en cada uno de los niveles que integran al individuo, en un nivel emocional, psicológico, fisiológico, de comportamiento y psicopedagógico; en segundo lugar, los investigadores plantean diversas estrategias a nivel psicológico, pedagógico y socio ambiental con el objetivo principal de incrementar en el aprendiz una serie de recursos personales para hacer frente a la ansiedad. Comentamos las implicancias pedagógicas de estos resultados para una mejor comprensión de la ansiedad y del aprendizaje de una lengua extranjera.

Currículo, Infância e Educação Corporal: Fundamentos na perspectiva histórico-cultural e orientações no campo da interdisciplinaridade

Pós-graduação em Docência para a Educação Básica - FC

Currículo, Infância e Educação Corporal: Fundamentos na perspectiva histórico-cultural e orientações no campo da interdisciplinaridade

Pós-graduação em Docência para a Educação Básica - FC

Role of MicroRNA Modulation in the Interferon-α/Ribavirin Suppression of HIV-1 In Vivo.

BACKGROUND Interferon-α (IFN-α) treatment suppresses HIV-1 viremia and reduces the size of the HIV-1 latent reservoir. Therefore, investigation of the molecular and immunologic effects of IFN-α may provide insights that contribute to the development of novel prophylactic, therapeutic and curative strategies for HIV-1 infection. In this study, we hypothesized that microRNAs (miRNAs) contribute to the IFN-α-mediated suppression of HIV-1. To inform the development of novel miRNA-based antiretroviral strategies, we investigated the effects of exogenous IFN-α treatment on global miRNA expression profile, HIV-1 viremia, and potential regulatory networks between miRNAs and cell-intrinsic anti-HIV-1 host factors in vivo. METHODS Global miRNA expression was examined in longitudinal PBMC samples obtained from seven HIV/HCV-coinfected, antiretroviral therapy-naïve individuals before, during, and after pegylated interferon-α/ribavirin therapy (IFN-α/RBV). We implemented novel hybrid computational-empirical approaches to characterize regulatory networks between miRNAs and anti-HIV-1 host restriction factors. RESULTS miR-422a was the only miRNA significantly modulated by IFN-α/RBV in vivo (p<0.0001, paired t test; FDR<0.037). Our interactome mapping revealed extensive regulatory involvement of miR-422a in p53-dependent apoptotic and pyroptotic pathways. Based on sequence homology and inverse expression relationships, 29 unique miRNAs may regulate anti-HIV-1 restriction factor expression in vivo. CONCLUSIONS The specific reduction of miR-422a is associated with exogenous IFN-α treatment, and likely contributes to the IFN-α suppression of HIV-1 through the enhancement of anti-HIV-1 restriction factor expression and regulation of genes involved in programmed cell death. Moreover, our regulatory network analysis presents additional candidate miRNAs that may be targeted to enhance anti-HIV-1 restriction factor expression in vivo.

Word Formation in South American Languages

This volume focuses on word formation processes in smaller and so far underrepresented indigenous languages of South America. The data for the analyses have been mainly collected in the field by the authors. The several language families described here, among them Arawakan, Takanan, and Guaycuruan, as well as language isolates, such as Yurakaré and Cholón, reflect the linguistic diversity of South America. Equally diverse are the topics addressed, relating to word formation processes like reduplication, nominal and verbal compounding, clitic compounding, and incorporation. The traditional notions of the processes are discussed critically with respect to their implementation in minor indigenous languages. The book is therefore not only of interest to readers with an Amerindian background but also to typologists and historical linguists, and it is a supplement to more theory-driven approaches to language and linguistics.

Materials properties from electron density distributions: Molecular magnetism and linear optical properties

The general goal of this thesis is correlating observable properties of organic and metal-organic materials with their ground-state electron density distribution. In a long-term view, we expect to develop empirical or semi-empirical approaches to predict materials properties from the electron density of their building blocks, thus allowing to rationally engineering molecular materials from their constituent subunits, such as their functional groups. In particular, we have focused on linear optical properties of naturally occurring amino acids and their organic and metal-organic derivatives, and on magnetic properties of metal-organic frameworks. For analysing the optical properties and the magnetic behaviour of the molecular or sub-molecular building blocks in materials, we mostly used the more traditional QTAIM partitioning scheme of the molecular or crystalline electron densities, however, we have also investigated a new approach, namely, X-ray Constrained Extremely Localized Molecular Orbitals (XC-ELMO), that can be used in future to extracted the electron densities of crystal subunits. With the purpose of rationally engineering linear optical materials, we have calculated atomic and functional group polarizabilities of amino acid molecules, their hydrogen-bonded aggregates and their metal-organic frameworks. This has enabled the identification of the most efficient functional groups, able to build-up larger electric susceptibilities in crystals, as well as the quantification of the role played by intermolecular interactions and coordinative bonds on modifying the polarizability of the isolated building blocks. Furthermore, we analysed the dependence of the polarizabilities on the one-electron basis set and the many-electron Hamiltonian. This is useful for selecting the most efficient level of theory to estimate susceptibilities of molecular-based materials. With the purpose of rationally design molecular magnetic materials, we have investigated the electron density distributions and the magnetism of two copper(II) pyrazine nitrate metal-organic polymers. High-resolution X-ray diffraction and DFT calculations were used to characterize the magnetic exchange pathways and to establish relationships between the electron densities and the exchange-coupling constants. Moreover, molecular orbital and spin-density analyses were employed to understand the role of different magnetic exchange mechanisms in determining the bulk magnetic behaviour of these materials. As anticipated, we have finally investigated a modified version of the X-ray constrained wavefunction technique, XC-ELMOs, that is not only a useful tool for determination and analysis of experimental electron densities, but also enables one to derive transferable molecular orbitals strictly localized on atoms, bonds or functional groups. In future, we expect to use XC-ELMOs to predict materials properties of large systems, currently challenging to calculate from first-principles, such as macromolecules or polymers. Here, we point out advantages, needs and pitfalls of the technique. This work fulfils, at least partially, the prerequisites to understand materials properties of organic and metal-organic materials from the perspective of the electron density distribution of their building blocks. Empirical or semi-empirical evaluation of optical or magnetic properties from a preconceived assembling of building blocks could be extremely important for rationally design new materials, a field where accurate but expensive first-principles calculations are generally not used. This research could impact the community in the fields of crystal engineering, supramolecular chemistry and, of course, electron density analysis.

The dangers of theorizing before analysis : four case studies about argumentation and cognition

International audience