Transcriptional Enhancers in Protein-Coding Exons of Vertebrate Developmental Genes

Many conserved noncoding sequences function as transcriptional enhancers that regulate gene expression. Here, we report that protein-coding DNA also frequently contains enhancers functioning at the transcriptional level. We tested the enhancer activity of 31 protein-coding exons, which we chose based on strong sequence conservation between zebrafish and human, and occurrence in developmental genes, using a Tol2 transposable GFP reporter assay in zebrafish. For each exon we measured GFP expression in hundreds of embryos in 10 anatomies via a novel system that implements the voice-recognition capabilities of a cellular phone. We find that 24/31 (77%) exons drive GFP expression compared to a minimal promoter control, and 14/24 are anatomy-specific (expression in four anatomies or less). GFP expression driven by these coding enhancers frequently overlaps the anatomies where the host gene is expressed (60%), suggesting self-regulation. Highly conserved coding sequences and highly conserved noncoding sequences do not significantly differ in enhancer activity (coding: 24/31 vs. noncoding: 105/147) or tissue-specificity (coding: 14/24 vs. noncoding: 50/105). Furthermore, coding and noncoding enhancers display similar levels of the enhancer-related histone modification H3K4me1 (coding: 9/24 vs noncoding: 34/81). Meanwhile, coding enhancers are over three times as likely to contain an H3K4me1 mark as other exons of the host gene. Our work suggests that developmental transcriptional enhancers do not discriminate between coding and noncoding DNA and reveals widespread dual functions in protein-coding DNA

R.D. Laing and theology: the influence of Christian existentialism on The Divided Self

The radical psychiatrist R. D. Laing's first book, The Divided Self (1960), is informed by the work of Christian thinkers on scriptural interpretation — an intellectual genealogy apparent in Laing's comparison of Karl Jaspers's symptomatology with the theological tradition of `form criticism'. Rudolf Bultmann's theology, which was being enthusiastically promoted in 1950s Scotland, is particularly influential upon Laing. It furnishes him with the notion that schizophrenic speech expresses existential truths as if they were statements about the physical and organic world. It also provides him with a model of the schizoid position as a form of modern-day Stoicism. Such theological recontextualization of The Divided Self illuminates continuities in Laing's own work, and also indicates his relationship to a wider British context, such as the work of the `clinical theologian' Frank Lake

A Stress-Criterion-Based Model for the Prediction of the Size of Wear Particles in Boundary Lubricated Contacts

In this paper, the formulation and validation of a model for the prediction of the wear particles size in boundary lubrication is described. An efficient numerical model based on a well-established BEM formulation combined with a mechanical wear criterion was applied. The behavior of the model and particularly the influence of the initial surface roughness and load was explored. The model was validated using measurements of the wear particles formed in steel–steel and steel–brass contacts. In the case of steel–steel contact, a reasonable quantitative agreement was observed. In the case of steel–brass contact, formation of the brass transfer layer dominates the particles generation process. To include this effect, a layered material model was introduced