Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism

The effect of feto-maternal size and childhood growth on left ventricular mass and arterial stiffness in Afro-Caribbean children

We hypothesized that maternal size, fetal size and childhood growth are associated with childhood blood pressure, left ventricular mass (LVM) and arterial stiffness. The Vulnerable Windows Cohort is a longitudinal study of 569 mothers and their offspring. Anthropometry was measured on each child at birth, at 6 weeks, once in 3 months upto 2 years and then every 6 months. Blood pressure and body composition were assessed in 185 children (age 11.5 years) and echocardiography performed. LVM was not associated with maternal size after adjustment for child's weight. LVM was significantly associated with faster growth in childhood and with current weight, fat mass and lean mass. Systolic blood pressure was not related to maternal, fetal or newborn anthropometry, but was positively associated with infant and childhood growth, as well as current body size and fat mass. The pulse pressure/stroke volume ratio (an index of arterial stiffness) was inversely associated with maternal size, placental volume at 20 weeks, fetal size at 35 weeks and childhood growth even after adjustment for current weight. In conclusion, LVM in childhood is positively associated with maternal height, child's current size and rate of growth. Arterial stiffness is inversely related to maternal, fetal and placental size as well as growth throughout childhood.<br/

Transgressive desires: new enterprising selves in the new capitalism

The growth of self-employed enterprise and the supposed ascendancy of the 'enterprising self' are commonly associated with the forces of flexibilization and individualization in contemporary work arrangements. What is driving these forces and their effects can be understood, in part, by examining what psychoanalytic theory would name desire. The focus here is upon the dynamics of desire among individuals who leave jobs to enter the growing ranks of the self-employed. Drawing from findings of a qualitative study of such new women entrepreneurs across Canada, changing concepts of the enterprising self are explored with specific attention to the relations between their desires and their conception of work. This article addresses three questions in particular: How is desire enmeshed in the development of enterprising selves? How do women come to desire work through self-employed enterprise, often entailing personal and economic pain? Do these desires configure possibilities for new alternatives in enterprise? The study findings suggest not only that contradictory desires are closely integrated with identity in the transition to enterprise, but also that some women's desires appear to form resistance to aspects of conventional models of business development. Through analysis informed by psychoanalytic theories of desire, these impulses are named 'transgressive desires' and their importance is demonstrated in their links to the new models of entrepreneurism that seem to be appearing among these women's enterprises