“Take heed that ye offend not—despise not—hinder not—one of these little ones”: Charlotte Mason and her educational proposal.

Charlotte Mason (1842–1923) was a well-known English educator whose work and legacy is certainly worthy of consideration today. One of the most interesting aspects of her philosophy of education is the fact that she adopts an anthropological approach: the consideration of the child as a person whose natural desire to know can only be satisfied with an education centered in the great books, the narrative method and the importance of relations. Her wide experience as a teacher, parental advisor, and teacher trainer, as well as the application of her method with surprisingly good results, constitute an endorsement of her proposal.pre-print432 K

Genome-wide analysis of the H3K27me3 epigenome and transcriptome in brassica rapa

Background Genome-wide maps of histone modifications have been obtained for several plant species. However, most studies focus on model systems and do not enforce FAIR data management principles. Here we study the H3K27me3 epigenome and associated transcriptome of Brassica rapa, an important vegetable cultivated worldwide. Findings We performed H3K27me3 chromatin immunoprecipitation followed by high-throughput sequencing and transcriptomic analysis by 3′-end RNA sequencing from B. rapa leaves and inflorescences. To analyze these data we developed a Reproducible Epigenomic Analysis pipeline using Galaxy and Jupyter, packaged into Docker images to facilitate transparency and reuse. We found that H3K27me3 covers roughly one-third of all B. rapa protein-coding genes and its presence correlates with low transcript levels. The comparative analysis between leaves and inflorescences suggested that the expression of various floral regulatory genes during development depends on H3K27me3. To demonstrate the importance of H3K27me3 for B. rapa development, we characterized a mutant line deficient in the H3K27 methyltransferase activity. We found that braA.clf mutant plants presented pleiotropic alterations, e.g., curly leaves due to increased expression and reduced H3K27me3 levels at AGAMOUS-like loci. Conclusions We characterized the epigenetic mark H3K27me3 at genome-wide levels and provide genetic evidence for its relevance in B. rapa development. Our work reveals the epigenomic landscape of H3K27me3 in B. rapa and provides novel genomics datasets and bioinformatics analytical resources. We anticipate that this work will lead the way to further epigenomic studies in the complex genome of Brassica crops

¿Tiempos Difíciles? La digitalización de la enseñanza

The Digital Revolution has brought along dramatic transformations in almost every sphere of human existence. Education stands out as one of the domains most deeply influenced by the arrival of the digital technologies, whose implementation in schools is being hotly debated. Unfortunately, the debate is often clouded by commercial interests and political agendas. The scientific and empirical evidences are frequently concealed or manipulated in order to support such or such other stance. Besides, the inaccurate use of scientific terminology does not do anything but muddling the debate even more. Given the fundamental role of education in guaranteeing the welfare of any society, it is crucially important for the debate to take place apart from economic and political agendas, and firmly grounded on empirical and scientific evidences. For that to happen, it is necessary, first, to turn to the sources and review the available evidences; and second, to come to terms and provide a scientific framework useful for the analysis of the evidence. These are precisely the aims of the present master thesis.La revolución digital ha traído consigo profundas transformaciones en casi todos los ámbitos de la existencia humana. Entre ellos, la educación se destaca como uno de los más afectados por la llegada de las tecnologías digitales, cuya implantación en las aulas está siendo objeto de un encendido e intrincado debate. Intereses económicos y agendas políticas oscurecen las evidencias científicas, que son ignoradas, ocultadas y manipuladas con el fin de favorecer tal o cual postura del debate. El empleo poco riguroso de terminología científica no hace sino enturbiar aún más las cosas. Dada el papel fundamental que juega la educación en el bienestar de toda sociedad, es de vital importancia que el debate transcurra al margen de intereses económicos y partidistas, y que esté sustentado en evidencias científicas y empíricas. Para lograrlo, es necesario, en primer lugar, acudir directamente a las fuentes y revisar las evidencias disponibles; y en segundo lugar, aclarar términos y ofrecer un marco científico que facilite la interpretación de tales evidencias. Estos son, precisamente, los objetivos del presente trabajo

DddD Is a CoA-Transferase/Lyase Producing Dimethyl Sulfide in the Marine Environment

Dimethyl sulfide (DMS) is produced in oceans in vast amounts (>10⁷ tons/year) and mediates a wide range of processes from regulating marine life forms to cloud formation. Nonetheless, none of the enzymes that produce DMS from dimethylsulfoniopropionate (DMSP) has been adequately characterized. We describe the expression and purification of DddD from the marine bacterium <i>Marinomonas</i> sp. MWYL1 and its biochemical characterization. We identified DMSP and acetyl-coenzyme A to be DddD’s native substrates and Asp602 as the active site residue mediating the CoA-transferase prior to lyase activity. These findings shed light on the biochemical utilization of DMSP in the marine environment

Genome-wide analysis of the H3K27me3 epigenome and transcriptome in brassica rapa

Background Genome-wide maps of histone modifications have been obtained for several plant species. However, most studies focus on model systems and do not enforce FAIR data management principles. Here we study the H3K27me3 epigenome and associated transcriptome of Brassica rapa, an important vegetable cultivated worldwide. Findings We performed H3K27me3 chromatin immunoprecipitation followed by high-throughput sequencing and transcriptomic analysis by 3′-end RNA sequencing from B. rapa leaves and inflorescences. To analyze these data we developed a Reproducible Epigenomic Analysis pipeline using Galaxy and Jupyter, packaged into Docker images to facilitate transparency and reuse. We found that H3K27me3 covers roughly one-third of all B. rapa protein-coding genes and its presence correlates with low transcript levels. The comparative analysis between leaves and inflorescences suggested that the expression of various floral regulatory genes during development depends on H3K27me3. To demonstrate the importance of H3K27me3 for B. rapa development, we characterized a mutant line deficient in the H3K27 methyltransferase activity. We found that braA.clf mutant plants presented pleiotropic alterations, e.g., curly leaves due to increased expression and reduced H3K27me3 levels at AGAMOUS-like loci. Conclusions We characterized the epigenetic mark H3K27me3 at genome-wide levels and provide genetic evidence for its relevance in B. rapa development. Our work reveals the epigenomic landscape of H3K27me3 in B. rapa and provides novel genomics datasets and bioinformatics analytical resources. We anticipate that this work will lead the way to further epigenomic studies in the complex genome of Brassica crops

Conserved and distinct roles of H3K27me3 demethylases regulating flowering time in Brassica rapa

14 Pág.Epigenetic regulation is necessary for optimal organism development and preservation of gene expression profiles in the cell. In plants, the trimethylation of histone H3 lysine 27 (H3K27me3) is a silencing epigenetic mark relevant for developmental transitions like flowering. The floral transition is a key agronomic trait; however, the epigenetic mechanisms of flowering time regulation in crops remain poorly understood. Here we study the Jumonji H3K27me3 demethylases BraA.REF6 and BraA.ELF6 in Brassica rapa. Phenotypic characterization of novel mutant lines and genome-wide H3K27me3 chromatin immunoprecipitation and transcriptomic analyses indicated that BraA.REF6 plays a greater role than BraA.ELF6 in fine-tuning H3K27me3 levels. In addition, we found that braA.elf6 mutants were early flowering due to high H3K27me3 levels at B. rapa homologs of the floral repressor FLC. Unlike mutations in Arabidopsis thaliana, braA.ref6 mutants were late flowering without altering the expression of B. rapa FLC genes. Remarkably, we found that BraA.REF6 regulated a number of gibberellic acid (GA) biosynthetic genes, including a homolog of GA1, and that GA-treatment complemented the late flowering mutant phenotype. This study increases our understanding of the epigenetic regulation of flowering time in B. rapa, highlighting conserved and distinct regulatory mechanisms between model and crop species.This study was supported by grants BIO2015-68031-R and RTI2018-097749-B-I00 to PC, and PID2019-104899GB-I00 to JAJ and MP from MCIN/AEI/10.13039/501100011033 and FEDER; and fellowships BES-2016-078939 to LP and RYC-2013-14689 to PC from MCIN/AEI/10.13039/501100011033 and FSE. MPM was supported by a Postdoctoral contract associated to the “Severo Ochoa Program for Centres of Excellence in R&D” grant SEV-2016-0672 (2017–2021) to CBGP from MCIN/AEI/10.13039/501100011033.Peer reviewe

Mutational synergy during leukemia induction remodels chromatin accessibility, histone modifications and three-dimensional DNA topology to alter gene expression.

Altered transcription is a cardinal feature of acute myeloid leukemia (AML); however, exactly how mutations synergize to remodel the epigenetic landscape and rewire three-dimensional DNA topology is unknown. Here, we apply an integrated genomic approach to a murine allelic series that models the two most common mutations in AML: Flt3-ITD and Npm1c. We then deconvolute the contribution of each mutation to alterations of the epigenetic landscape and genome organization, and infer how mutations synergize in the induction of AML. Our studies demonstrate that Flt3-ITD signals to chromatin to alter the epigenetic environment and synergizes with mutations in Npm1c to alter gene expression and drive leukemia induction. These analyses also allow the identification of long-range cis-regulatory circuits, including a previously unknown superenhancer of Hoxa locus, as well as larger and more detailed gene-regulatory networks, driven by transcription factors including PU.1 and IRF8, whose importance we demonstrate through perturbation of network members.Cancer Research UK, European Research Council, Wellcome Trust, Kay Kendall Leukaemia Fund, American Society of Haematolog

MED12 Regulates HSC-Specific Enhancers Independently of Mediator Kinase Activity to Control Hematopoiesis

Hematopoietic-specific transcription factors require coactivators to communicate with the general transcription machinery and establish transcriptional programs that maintain hematopoietic stem cell (HSC) self-renewal, promote differentiation, and prevent malignant transformation. Mediator is a large coactivator complex that bridges enhancer-localized transcription factors with promoters, but little is known about Mediator function in adult stem cell self-renewal and differentiation. We show that MED12, a member of the Mediator kinase module, is an essential regulator of HSC homeostasis, as in vivo deletion of Med12 causes rapid bone marrow aplasia leading to acute lethality. Deleting other members of the Mediator kinase module does not affect HSC function, suggesting kinase-independent roles of MED12. MED12 deletion destabilizes P300 binding at lineage-specific enhancers, resulting in H3K27Ac depletion, enhancer de-activation, and consequent loss of HSC stemness signatures. As MED12 mutations have been described recently in blood malignancies, alterations in MED12-dependent enhancer regulation may control both physiological and malignant hematopoiesis