Rapid cohort generation and analysis of disease spectrum of large animal model of cone dystrophy.

Large animal models are an important resource for the understanding of human disease and for evaluating the applicability of new therapies to human patients. For many diseases, such as cone dystrophy, research effort is hampered by the lack of such models. Lentiviral transgenesis is a methodology broadly applicable to animals from many different species. When conjugated to the expression of a dominant mutant protein, this technology offers an attractive approach to generate new large animal models in a heterogeneous background. We adopted this strategy to mimic the phenotype diversity encounter in humans and generate a cohort of pigs for cone dystrophy by expressing a dominant mutant allele of the guanylate cyclase 2D (GUCY2D) gene. Sixty percent of the piglets were transgenic, with mutant GUCY2D mRNA detected in the retina of all animals tested. Functional impairment of vision was observed among the transgenic pigs at 3 months of age, with a follow-up at 1 year indicating a subsequent slower progression of phenotype. Abnormal retina morphology, notably among the cone photoreceptor cell population, was observed exclusively amongst the transgenic animals. Of particular note, these transgenic animals were characterized by a range in the severity of the phenotype, reflecting the human clinical situation. We demonstrate that a transgenic approach using lentiviral vectors offers a powerful tool for large animal model development. Not only is the efficiency of transgenesis higher than conventional transgenic methodology but this technique also produces a heterogeneous cohort of transgenic animals that mimics the genetic variation encountered in human patients

Too Much Feeling : SE Hinton's The Outsiders (1967), Conflicting Emotions, Identity, and Socialization

This article argues that emotions are utilized for norm breaking, identity formation, and socialization in S.E. Hinton's YA novel The Outsiders (1967). Drawing on the history of emotions studies, it investigates how emotional expressions are utilized to negotiate and contest given emotional norms on the one hand, and Young Adult literary conventions on the other. The point of departure is intersectional and focuses on the relationship between emotion, power, and socialization. In particular, the article considers how intersections of age, gender, and class relate to depictions of feeling and establishing of new emotional norms. The article shows that the feelings that the main character Pony expresses are part of a reiterative process of negotiation of power; they work as instruments for changing emotional norms connected to his age, class, and gender