\u27What Fresh Hell …?\u27 Cultus in Dickinson Garland, Piaf and Weil

Dorothy Parker created a heroine who responded to the ringing of her doorbell, What fresh hell can this be? In a sense, Parker\u27s question suggests the cultic appeal of women otherwise as diverse as Emily Dickinson, Judy Garland, Edith Piaf, and Simone Weil. Indeed, Dickinson\u27s epigrammatic couplet, Parting is all we know of heaven,/ And all we need of hell, somehow describes the dilemma all four women confronted for their variously admiring Bog[s]. In 1938, Simone Weil wrote a letter to Georges Bernanos on the occasion of the latter\u27s Les Grandes Cimetieres Sous la Lune, an account of France\u27s offensive in Spain: I recognized the smell of civil war, the smell of blood and terror, which exhales from your book; I have breathed it, too. Knowing hell and telling is the somehow redeeming power of Garland and Piaf as well. The child Garland had helped inspire the words of Over the Rainbow : Fantasy had been for her the only reality she knew, and she was trying always to chase these fantasies and seize them—and what was fantasy at its most pure but yearning for what lay on the other side of the rainbow in the sky? … All four women stress a brave continuity whatever the hellish discontinuities of life. The similarities of these four women will be defined according to Dickinson\u27s terms. It is as if she were one of the very first of their modern kind of pop and/or high cultists

Micrococcal Nuclease Does Not Substantially Bias Nucleosome Mapping

We have mapped sequence-directed nucleosome positioning on genomic DNA molecules using high-throughput sequencing. Chromatins, prepared by reconstitution with either chicken or frog histones, were separately digested to mononucleosomes using either micrococcal nuclease (MNase) or caspase-activated DNase (CAD). Both enzymes preferentially cleave internucleosomal (linker) DNA, although they do so by markedly different mechanisms. MNase has hitherto been very widely used to map nucleosomes, although concerns have been raised over its potential to introduce bias. Having identified the locations and quantified the strength of both the chicken or frog histone octamer binding sites on each DNA, the results obtained with the two enzymes were compared using a variety of criteria. Both enzymes displayed sequence specificity in their preferred cleavage sites, although the nature of this selectivity was distinct for the two enzymes. In addition, nucleosomes produced by CAD nuclease are 8–10 bp longer than those produced with MNase, with the CAD cleavage sites tending to be 4–5 bp further out from the nucleosomal dyad than the corresponding MNase cleavage sites. Despite these notable differences in cleavage behaviour, the two nucleases identified essentially equivalent patterns of nucleosome positioning sites on each of the DNAs tested, an observation that was independent of the histone type. These results indicate that biases in nucleosome positioning data collected using MNase are, under our conditions, not significant

Development of primary invasive pneumococcal disease caused by serotype 1 pneumococci is driven by early increased type I interferon response in the lung

The pneumococcus is the world's foremost respiratory pathogen, but the mechanisms allowing this pathogen to proceed from initial asymptomatic colonization to invasive disease are poorly understood. We have examined the early stages of invasive pneumococcal disease (IPD) by comparing host transcriptional responses to an invasive strain and a noninvasive strain of serotype 1 Streptococcus pneumoniae in the mouse lung. While the two strains were present in equal numbers in the lung 6 h after intranasal challenge, only the invasive strain (strain 1861) had invaded the pleural cavity at that time point; this correlated with subsequent development of bacteremia in mice challenged with strain 1861 but not the noninvasive strain (strain 1). Progression beyond the lung was associated with stronger induction of the type I interferon (IFN-I) response in the lung at 6 h. Suppression of the IFN-I response through administration of neutralizing antibody to IFNAR1 (the receptor for type I interferons) led to significantly reduced invasion of the pleural cavity by strain 1861 at 6 h postchallenge. Our data suggest that strong induction of the IFN-I response is a key factor in early progression of invasive serotype 1 strain 1861 beyond the lung during development of IPD