Tbx20 Is Required in Mid-Gestation Cardiomyocytes and Plays a Central Role in Atrial Development.

RationaleMutations in the transcription factor TBX20 (T-box 20) are associated with congenital heart disease. Germline ablation of Tbx20 results in abnormal heart development and embryonic lethality by embryonic day 9.5. Because Tbx20 is expressed in multiple cell lineages required for myocardial development, including pharyngeal endoderm, cardiogenic mesoderm, endocardium, and myocardium, the cell type-specific requirement for TBX20 in early myocardial development remains to be explored.ObjectiveHere, we investigated roles of TBX20 in midgestation cardiomyocytes for heart development.Methods and resultsAblation of Tbx20 from developing cardiomyocytes using a doxycycline inducible cTnTCre transgene led to embryonic lethality. The circumference of developing ventricular and atrial chambers, and in particular that of prospective left atrium, was significantly reduced in Tbx20 conditional knockout mutants. Cell cycle analysis demonstrated reduced proliferation of Tbx20 mutant cardiomyocytes and their arrest at the G1-S phase transition. Genome-wide transcriptome analysis of mutant cardiomyocytes revealed differential expression of multiple genes critical for cell cycle regulation. Moreover, atrial and ventricular gene programs seemed to be aberrantly regulated. Putative direct TBX20 targets were identified using TBX20 ChIP-Seq (chromatin immunoprecipitation with high throughput sequencing) from embryonic heart and included key cell cycle genes and atrial and ventricular specific genes. Notably, TBX20 bound a conserved enhancer for a gene key to atrial development and identity, COUP-TFII/Nr2f2 (chicken ovalbumin upstream promoter transcription factor 2/nuclear receptor subfamily 2, group F, member 2). This enhancer interacted with the NR2F2 promoter in human cardiomyocytes and conferred atrial specific gene expression in a transgenic mouse in a TBX20-dependent manner.ConclusionsMyocardial TBX20 directly regulates a subset of genes required for fetal cardiomyocyte proliferation, including those required for the G1-S transition. TBX20 also directly downregulates progenitor-specific genes and, in addition to regulating genes that specify chamber versus nonchamber myocardium, directly activates genes required for establishment or maintenance of atrial and ventricular identity. TBX20 plays a previously unappreciated key role in atrial development through direct regulation of an evolutionarily conserved COUPT-FII enhancer

EXPERIMENTAL STUDY ON THE PRESENCE OF OPEN CAVITY EFFECTS ON INTERNAL FLOW AND CONVECTIONHEAT TRANSFER CHARACTERISTICS

An experimental study is conducted to investigate the effect of open cavity on the pattern of fully developed internal flow and convection heat transfer. In this experimental work the velocity profile, temperature distribution, heat transfer coefficient and Nusselt number were determined at various Reynolds numbers (1.9*104≤ Re ≤ 2.7*104 ) for smooth surface as well as for flow over open cavity (with and without excitation). The results showed that the presence of the cavity led to change the downstream velocity profile and the dissimilarity of downstream skin friction coefficient between the upper and lower surfaces around (64 %) at distance to the length cavity (x/L= + 20.5). As a result the heat transfer coefficient and Nu increased downstream of the cavity especially at (x/L= + 20.5) around (30 %). The effect of cavity excitation with different  sound levels (100,107.5 and 115) dB and frequencies (25,50 and 100) Hz was small compared with the cavity itself.

Addressing educational needs of teachers in the EU for inclusive education in a context of diversity Volume 3, Part 2: overview of 21 innovative cases for the development of intercultural and democratic competences in teacher education

In spite of policy impetus, research shows that teachers struggle to address the increasing diversity in classrooms, among others, due to the lack of competences to deal with it. The acquisition of Intercultural Competence (IC), which the ability to mobilise and deploy relevant attitudes, skills, knowledge and values in order to interact effectively and appropriately in different intercultural situations to be successful in their teaching. In this context, in 2019 the JRC launched the INNO4DIV project with the aim to support polices in the field of IC of teachers, through the analysis of literature and innovative good practices which have successfully addressed the existing barriers for teacher´s IC development. The initial project reports provide the conceptual framework of the project, Competence: Working definition and implications for teacher education (Shuali et al., 2020), and the results of the literature review, Volume 2. Literature review on competence development and their associated barriers (Simó et al., 2020). The methodology for the selection and assessment of innovative practices overcoming barriers in the development of intercultural and democratic competences was developed in the third report, Volume 3. Part 1: Assessment guidelines for teacher education and training practices on intercultural and democratic competence development. This report provides an overview of the 21 selected innovative cases for the development of intercultural and democratic competences in teacher education, which analysis has been the basis to extract lessons learnt in support of evidence based educational policy development. The results of this analysis and the recommendations provided will be published in INNO4DIV Volume 4, the final project report. This overview includes: the geographical scope of implementation, the sources of financial support, the diversity of stakeholders involved, the target groups addressed, the maturity of the cases in terms of duration, methodological alignment of the case with the Council of Europe Reference Framework for the Competence of Democratic Culture (CoE, 2016), the educational setting in which they take place (formal, non-formal education) and the number of participants (learners). Following the overview, the report provides a short description of each case including: the participating actors and countries, the project start/end dates and its implementation status, the geographical scope, the target audience, the different stakeholders involved, the background context, the case summary and the major findings with regards to the innovation carried out, the overcome barriers and the major case outcomes.Educació

Evolutionary comparison reveals that diverging CTCF sites are signatures of ancestral topological associating domains borders

Increasing evidence in the last years indicates that the vast amount of regulatory information contained in mammalian genomes is organized in precise 3D chromatin structures. However, the impact of this spatial chromatin organization on gene expression and its degree of evolutionary conservation is still poorly understood. The Six homeobox genes are essential developmental regulators organized in gene clusters conserved during evolution. Here, we reveal that the Six clusters share a deeply evolutionarily conserved 3D chromatin organization that predates the Cambrian explosion. This chromatin architecture generates two largely independent regulatory landscapes (RLs) contained in two adjacent topological associating domains (TADs). By disrupting the conserved TAD border in one of the zebrafish Six clusters, we demonstrate that this border is critical for preventing competition between promoters and enhancers located in separated RLs, thereby generating different expression patterns in genes located in close genomic proximity. Moreover, evolutionary comparison of Six-associated TAD borders reveals the presence of CCCTC-binding factor (CTCF) sites with diverging orientations in all studied deuterostomes. Genome-wide examination of mammalian HiC data reveals that this conserved CTCF configuration is a general signature of TAD borders, underscoring that common organizational principles underlie TAD compartmentalization in deuterostome evolution

Extensive pleiotropism and allelic heterogeneity mediate metabolic effects of IRX3 and IRX5

While coding variants often have pleiotropic effects across multiple tissues, non-coding variants are thought to mediate their phenotypic effects by specific tissue and temporal regulation of gene expression. Here, we dissected the genetic and functional architecture of a genomic region within the FTO gene that is strongly associated with obesity risk. We show that multiple variants on a common haplotype modify the regulatory properties of several enhancers targeting IRX3 and IRX5 from megabase distances. We demonstrate that these enhancers impact gene expression in multiple tissues, including adipose and brain, and impart regulatory effects during a restricted temporal window. Our data indicate that the genetic architecture of disease-associated loci may involve extensive pleiotropy, allelic heterogeneity, shared allelic effects across tissues, and temporally-restricted effects

PRAXIS: el Pràcticum al Grau de Pedagogia: mapa, simulació i immersió. (continuació).

El projecte d’innovació docent que presentem és la continuïtat del que es va atorgar el curs 2012-2013. Consta de la continuïtat en la implementació i anàlisi de la proposta d’innovació fonamentalment metodològica del Pràcticum al grau de Pedagogia, en les tres assignatures obligatòries que es troben coordinades sota una lògica de progressiva immersió en una institució de pràctiques. Així, la innovació que presentem per al present curs 2013-2014 es troba fonamentalment en la darrera assignatura de Pràctiques Externes, i alhora, dotant de coherència global en coordinació amb les altres dues assignatures. Durant el projecte PID anterior es van engegar les pràctiques externes, amb una mirada transdisciplinar, opten, per una part, per la immersió de l’alumnat en una organització, entesa la immersió com l'exposició intensiva d’aquest, a una organització. És una perspectiva sistèmica que considera les organitzacions com a sistemes complexos i holística perquè condueix a la integració unitària i globalitzadora de tots els coneixements de la persona. Per altra part, opten per sessions de pràctica reflexiva entre l’alumnat i el tutor de la universitat que han de permetre la transferència de coneixement, la reflexió al voltant de la relació existent entre el saber teòric i el saber experiencial en la vida professional. El tutor de la universitat i l’alumnat es reuniran per analitzar la pràctica, i les experiències de l’escenari professional. Durant aquest curs passat es va pilotar en dos tutores el portafolis digital per a l’avaluació de competències. La continuïtat pel proper curs ha estat d’implementar aquesta eina avaluativa a bona part del tutors. L’avaluació de les pràctiques es farà mitjançant la realització d’un portafolis digital, i implicarà l’autoavaluació de l’alumnat, la del tutor de l’organització de pràctiques, així com la del tutor de la universitat. També ens proposem, la sistematització i millora de les sessions de pràctica reflexiva, quant a la proposta temàtica relacionada amb els blocs de contingut i articulades al voltant de les diverses competències, tot donat continuïtat a les millores realitzades en el projecte d’innovació docent anterior. L’equip de coordinació del pràcticum i l’equip docent de l’assignatura de Pràctiques Externes ens proposem sistematitzar aquestes experiències i avaluar-les tot analitzant el seu potencial en l’alumnat pel desenvolupament de les competències que es plantegen en el pràcticum. També considerem fonamental donar continuïtat a les coordinacions de tot el conjunt del pràcticum implicant les altres dues assignatures: professionalització i sortides laborals i pràctiques d’iniciació professional. Donada la necessitat i valoracions rebudes entre els tres equips docents, pensem que s’ha de seguir apostant per aquesta via. En aquest sentit, l’aplicació de l’avaluació de competències transversals mitjançant el portafolis digital que aquest curs ho pilotarem a molts més grups de Pràctiques Externes, tenim la intencionalitat que en un futur sigui un recurs que acompanyi l’estudiantat en les tres assignatures. Finalment, consolidar la missió de constituir-nos com agents de transferència de coneixement. Actualment amb la programació d’una sèrie d’activitats institucionals que representaran l’inici d’una nova visió del Pràcticum de la Facultat de Pedagogia de la Universitat de Barcelona ho hem iniciat, però cal avançar més en aquesta direcció. És així com adquireix el sentit principal de seguir contribuint al ple desenvolupament com a persones, ciutadans i professionals dels nostres estudiants i a la millora de la competitivitat de les nostres empreses en un nou país més cohesionat, just i sostenible dins d’un món global i orientat al coneixement i la revalorització dels valors humans més fonamentals

Promoting More Physical Activity and Less Sedentary Behaviour During the COVID-19 Situation – SportStudisMoveYou (SSMY): A Randomized Controlled Trial

Objective: To determine the effect of an innovative, online-based intervention, addressing the possible decline of physical activity (PA) and increase of sedentary behavior (SB) during COVID-19 stay at home restrictions in Switzerland. Methods: This study investigated the effect of a two-week, social cognitive theory based, online-video moderate to vigorous (MV)PA or SB intervention on MVPA and SB behaviour and intention via a 3 group by 2 time point parallel randomized controlled trial during the COVID-19 pandemic. Adults (≥18 yo) were recruited over the internet between April 10th and April 19th 2020 (n = 129; 75.2% female; mean age = 29.0 [SD 11.8] years). Both intervention groups received five videos targeting either SB for the SB group or MVPA for the MVPA group and were compared to an attention control group (fruit and vegetable consumption). It was hypothesized that MVPA time and intention would increase for the MVPA group and the SB group would outperform control on SB behaviour and intention indicators. Results: No significant interactions were found for the MVPA group (n = 41) versus control (n = 40). Only one significant interaction was measured for the SB group (n = 48; intention of active breaks F = (2,114) = 5.84, p = 0.004, ηp2 = 0.09). Although mostly non-significant and small effects, the MVPA group showed results pointing in the hypothesized direction on all PA indicators and the SB on all SB indicators, respectively. Conclusion: Considering this study’s limitations (e.g. small intervention dose), video-based online PA and SB interventions seem promising and feasible. This approach is appropriate for COVID-19 and other stay at home situations

Asthma-associated genetic variants induce IL33 differential expression through an enhancer-blocking regulatory region

Genome-wide association studies (GWAS) have implicated the IL33 locus in asthma, but the underlying mechanisms remain unclear. Here, we identify a 5 kb region within the GWAS-defined segment that acts as an enhancer-blocking element in vivo and in vitro. Chromatin conformation capture showed that this 5 kb region loops to the IL33 promoter, potentially regulating its expression. We show that the asthma-associated single nucleotide polymorphism (SNP) rs1888909, located within the 5 kb region, is associated with IL33 gene expression in human airway epithelial cells and IL-33 protein expression in human plasma, potentially through differential binding of OCT-1 (POU2F1) to the asthma-risk allele. Our data demonstrate that asthma-associated variants at the IL33 locus mediate allele-specific regulatory activity and IL33 expression, providing a mechanism through which a regulatory SNP contributes to genetic risk of asthma.This work was supported by NIH grants R01 HL118758, R01 HL128075, R01 HL119577, R01 HL085197, U19 AI095230, UG3 OD023282 and UM1 AI114271

Transcriptome and regulatory maps of decidua-derived stromal cells inform gene discovery in preterm birth

While a genetic component of preterm birth (PTB) has long been recognized and recently mapped by genome-wide association studies (GWASs), the molecular determinants underlying PTB remain elusive. This stems in part from an incomplete availability of functional genomic annotations in human cell types relevant to pregnancy and PTB. We generated transcriptome (RNA-seq), epigenome (ChlP-seq of H3K27ac, H3K4mel, and H3K4me3 histone modifications), open chromatin (ATAC-seq), and chromatin interaction (promoter capture Hi-C) annotations of cultured primary decidua-derived mesenchymal stromal/stem cells and in vitro differentiated decidual stromal cells and developed a computational framework to integrate these functional annotations with results from a GWAS of gestational duration in 56,384 women. Using these resources, we uncovered additional loci associated with gestational duration and target genes of associated loci. Our strategy illustrates how functional annotations in pregnancy-relevant cell types aid in the experimental follow-up of GWAS for PTB and, likely, other pregnancy-related conditions.Peer reviewe