“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

Enhancing high-order harmonic generation in light molecules by using chirped pulses

One of the current challenges in high-harmonic generation is to extend the harmonic cutoff to increasingly high energies while maintaining or even increasing the efficiency of the high-harmonic emission. Here we show that the combined effect of down-chirped pulses and nuclear dynamics in light molecules allows one to achieve this goal, provided that long enough IR pulses are used to allow the nuclei to move well outside the Franck-Condon region. We also show that, by varying the duration of the chirped pulse or by performing isotopic substitution while keeping the pulse duration constant, one can control the extension of the harmonic plateauWe gratefully acknowledge fruitful discussions with Y.Mairesse. This work has been accomplished with a generous allocation of computer time from Mare Nostrum BSC and CCC-UAM and has been partially supported by the European Research Council Advanced Grant No. XCHEM 290853, MINECO Project No. FIS2013-42002-R, ERA-Chemistry Project No. PIM2010EEC-00751, European Grant No. MC-ITN CORINF, European COST Action XLIC CM1204, and the CAM project NANOFRONTMAG. R. E. F. S. acknowledges FCT—Fundação para a Ciência e Tecnologia, Portugal, Grant No. SFRH/BD/84053/201

Decoherence, control and attosecond probing of XUV-induced charge migration in biomolecules. A theoretical outlook

The sudden ionization of a molecule by an attosecond pulse is followed by charge redistribution on a time scale from a few femtoseconds down to hundreds of attoseconds. This ultrafast redistribution is the result of the coherent superposition of electronic continua associated with the ionization thresholds that are reached by the broadband attosecond pulse. Thus, a correct theoretical description of the time evolution of the ensuing wave packet requires the knowledge of the actual ionization amplitudes associated with all open ionization channels, a real challenge for large and medium-size molecules. Recently, the first calculation of this kind has come to light, allowing for interpretation of ultrafast electron dynamics observed in attosecond pump\u2013probe experiments performed on the amino acid phenylalanine [Calegari et al., Science 2014, 346, 336]. However, as in most previous theoretical works, the interpretation was based on various simplifying assumptions, namely, the ionized electron was not included in the description of the cation dynamics, the nuclei were fixed at their initial position during the hole migration process, and the effect of the IR probe pulse was ignored. Here we go a step further and discuss the consequences of including these effects in the photoionization of the glycine molecule. We show that (i) the ionized electron does not affect hole dynamics beyond the first femtosecond, and (ii) nuclear dynamics has only a significant effect after approximately 8 fs, but does not destroy the coherent motion of the electronic wave packet during at least few additional tens of fs. As a first step towards understanding the role of the probe pulse, we have considered an XUV probe pulse, instead of a strong IR one, and show that such an XUV probe does not introduce significant distortions in the pump-induced dynamics, suggesting that pump\u2013probe strategies are suitable for imaging and manipulating charge migration in complex molecules. Furthermore, we show that hole dynamics can be changed by shaping the attosecond pump pulse, thus opening the door to the control of charge dynamics in biomolecules

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

Genomic characterization of murine monocytes reveals C/EBPβ transcription factor dependence of Ly6C(-) cells

Monocytes are circulating, short-lived mononuclear phagocytes, which in mice and man comprise two main subpopulations. Murine Ly6C(+) monocytes display developmental plasticity and are recruited to complement tissue-resident macrophages and dendritic cells on demand. Murine vascular Ly6C(-) monocytes patrol the endothelium, act as scavengers, and support vessel wall repair. Here we characterized population and single cell transcriptomes, as well as enhancer and promoter landscapes of the murine monocyte compartment. Single cell RNA-seq and transplantation experiments confirmed homeostatic default differentiation of Ly6C(+) into Ly6C(-) monocytes. The main two subsets were homogeneous, but linked by a more heterogeneous differentiation intermediate. We show that monocyte differentiation occurred through de novo enhancer establishment and activation of pre-established (poised) enhancers. Generation of Ly6C(-) monocytes involved induction of the transcription factor C/EBP{beta} and C/EBP{beta}-deficient mice lacked Ly6C(-) monocytes. Mechanistically, C/EBP{beta} bound the Nr4a1 promoter and controlled expression of this established monocyte survival factor

Critical Modulation of Hematopoietic Lineage Fate by Hepatic Leukemia Factor.

A gradual restriction in lineage potential of multipotent stem/progenitor cells is a hallmark of adult hematopoiesis, but the underlying molecular events governing these processes remain incompletely understood. Here, we identified robust expression of the leukemia-associated transcription factor hepatic leukemia factor (Hlf) in normal multipotent hematopoietic progenitors, which was rapidly downregulated upon differentiation. Interference with its normal downregulation revealed Hlf as a strong negative regulator of lymphoid development, while remaining compatible with myeloid fates. Reciprocally, we observed rapid lymphoid commitment upon reduced Hlf activity. The arising phenotypes resulted from Hlf binding to active enhancers of myeloid-competent cells, transcriptional induction of myeloid, and ablation of lymphoid gene programs, with Hlf induction of nuclear factor I C (Nfic) as a functionally relevant target gene. Thereby, our studies establish Hlf as a key regulator of the earliest lineage-commitment events at the transition from multipotency to lineage-restricted progeny, with implications for both normal and malignant hematopoiesis.This work was generously supported by project grants to DB from the Swedish Cancer Society, the Swedish Medical Research Council, the Swedish Pediatric Leukemia Foundation, Knut and Alice Wallenberg foundation and an ERC consolidator grant (615068). We would like to acknowledge Tom Serwold, Ewa Sitnicka and Mikael Sigvardsson for valuable scientific discussions, and Eva Erlandsson and Gerd Sten for expert technical assistance. The Genome Technology Access Center, Department of Genetics, Washington University School of Medicine, assisted with genomic analysis and is partially supported by NCI Cancer Center Support Grant P30 CA91842 to the Siteman Cancer Center, ICTS/CTSA Grant UL1TR000448 from the National Center for Research Resources (NCRR, a component of the NIH), and the NIH Roadmap for Medical Research