Tinman/Nkx2-5 acts via miR-1 and upstream of Cdc42 to regulate heart function across species

Cdc42 regulates cardiac function in mice and flies downstream of a conserved Tinman/Nkx2-5–miR-1 signaling network

Rethinking the ethical and methodological dimensions of research with refugee children

This paper discusses the ethical and methodological dimensions of educational research with refugee children. The authors illustrate that research ethics need contextual, temporal and social flexibility to resonate with the changing needs and extraordinary contexts of this population, and that the flexibility is often too complex for ethical preassessments to address. The authors propose relational ethics, engaging with children and working from the "minds and hearts" rather than fixed ethical guidelines as one way to consider the ethics of working with this vulnerable population. (DIPF/Orig.)Dieser Artikel thematisiert die ethischen und methodologischen Dimensionen der Bildungsforschung mit geflüchteten Kindern. Die Autoren illustrieren, dass Forschungsethik kontextbezogene, zeitliche und soziale Flexibilität bedarf, um den sich ändernden Bedürfnissen und außergewöhnlichen Lebenskontexten dieser Personengruppe nachzukommen, und dass die Flexibilität häufig zu komplex ist, um ethische Vorannahmen zu adressieren. Die Autoren plädieren für eine relationale Ethik, die sich mit Kindern beschäftigt, in der Interaktion mit dem, Verstand und dem Herz\u27 der Kinder statt mit feststehenden ethischen Richtlinien, als eine Herangehensweise im Umgang mit den ethischen Fragen in der Arbeit mit dieser schutzbedürftigen Gruppe. (DIPF/Orig.

Renal developmental defects resulting from in utero hypoxia are associated with suppression of ureteric β-catenin signaling

Gestational stressors, including glucocorticoids and protein restriction, can affect kidney development and hence final nephron number. Since hypoxia is a common insult during pregnancy, we studied the influence of oxygen tension on kidney development in models designed to represent a pathological hypoxic insult. In vivo mouse models of moderate, transient, midgestational (12% O-2, 48 h, 12.5 dpc) or severe, acute, early-gestational (5.5-7.5% O-2, 8 h, 9.5-10.5 dpc) hypoxia were developed. The embryo itself is known to mature under hypoxic conditions with embryonic tissue levels of oxygen estimated to be 5%-8% (physiological hypoxia) when the mother is exposed to ambient normoxia. Both in vivo models generated phenotypes seen in patients with congenital anomalies of the kidney and urinary tract (CAKUT). Severe, acute, early hypoxia resulted in duplex kidney, while moderate, transient, midgestational hypoxia permanently reduced ureteric branching and nephron formation. Both models displayed hypoxia-induced reductions in beta-catenin signaling within the ureteric tree and suppression of the downstream target gene, Ccnd1. Thus, we show a link between gestational hypoxia and CAKUT, the phenotype of which varies with timing, duration, and severity of the hypoxic insult

A Diagnosis for All Rare Genetic Diseases: The Horizon and the Next Frontiers.

The introduction of exome sequencing in the clinic has sparked tremendous optimism for the future of rare disease diagnosis, and there is exciting opportunity to further leverage these advances. To provide diagnostic clarity to all of these patients, however, there is a critical need for the field to develop and implement strategies to understand the mechanisms underlying all rare diseases and translate these to clinical care

A diagnosis for all rare genetic diseases: the horizon and the next frontiers

The introduction of exome sequencing in the clinic has sparked tremendous optimism for the future of rare disease diagnosis, and there is exciting opportunity to further leverage these advances. To provide diagnostic clarity to all of these patients, however, there is a critical need for the field to develop and implement strategies to understand the mechanisms underlying all rare diseases and translate these to clinical care.</p