Male 41, XXY* mice as a model for Klinefelter syndrome: Hyperactivation of Leydig cells

Sex chromosome imbalance in males is linked to a supernumerary X chromosome, a condition resulting in Klinefelter syndrome (KS; 47, XXY). KS patients suffer from infertility, hypergonadotropic hypogonadism, and cognitive impairments. Mechanisms of KS pathophysiology are poorly understood and require further exploration using animal models. Therefore, we phenotypically characterized 41, XX(Y)* mice of different ages, evaluated observed germ cell loss, studied X-inactivation, and focused on the previously postulated impaired Leydig cell maturation and function as a possible cause of the underandrogenization seen in KS. Xist methylation analysis revealed normal X-chromosome inactivation similar to that seen in females. Germ cell loss was found to be complete and to occur during the peripubertal phase. Significantly elevated FSH and LH levels were persistent in 41, XX(Y)* mice of different ages. Although Leydig cell hyperplasia was prominent, isolated XX(Y)* Leydig cells showed a mature mRNA expression profile and a significantly higher transcriptional activity compared with controls. Stimulation of XX(Y)* Leydig cells in vitro by human chorionic gonadotropin indicated a mature LH receptor whose maximal response exceeded that of control Leydig cells. The hyperactivity of Leydig cells seen in XX(Y)* mice suggests that the changes in the endocrine milieu observed in KS is not due to impaired Leydig cell function. We suggest that the embedding of Leydig cells into the changed testicular environment in 41 XX(Y)* males as such influences their endocrine function

Does the performance of TDD hold across software companies and premises?:a group of industrial experiments on TDD

Abstract Test-Driven Development (TDD) has been claimed to increase external software quality. However, the extent to which TDD increases external quality has been seldom studied in industrial experiments. We conduct four industrial experiments in two different companies to evaluate the performance of TDD on external quality. We study whether the performance of TDD holds across the premises of the same company and across companies. We identify participant-level characteristics impacting results. Iterative-Test Last (ITL), the reverse approach of TDD, outperforms TDD in three out of four premises. ITL outperforms TDD in both companies. The larger the experience with unit testing and testing tools, the larger the difference in performance between ITL and TDD (in favour of ITL). Technological environment (i.e., programming language and testing tool) seems not to impact results. Evaluating participant-level characteristics impacting results in industrial experiments may ease the understanding of TDD’s performance in realistic settings