Inductive signals cause conversion of mesenchyme into epithelia during the formation of many organs. Yet a century of study has not revealed the inducing molecules. Using a standard model of induction, we found that ureteric bud cells secrete factors that convert kidney mesenchyme to epithelia that, remarkably, then form nephrons. Purification and sequencing of one such factor identified it as leukemia inhibitory factor (LIF). LIF acted on epithelial precursors that we identified by the expression of Pax2 and Wnt4. Other IL-6 type cytokines acted like LIF, and deletion of their shared receptor reduced nephron development. In situ, the ureteric bud expressed LIF, and metanephric mesenchyme expressed its receptors. The data suggest that IL-6 cytokines are candidate regulators of mesenchymal to epithelial conversion during kidney development.

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We sought to determine the rate of spontaneous closure of the ductus arteriosus (DA) in very-low-birth-weight infants. This prospective observational study included 65 infants whose birth weight (BW) < 1500 g. Echocardiograms were done on day of life (DOL) 3 and 7, weekly for the first month, and bimonthly until ligation, discharge, or death. Treatment was reserved for infants with heart failure, acute renal impairment, or those with significant persistent or escalating respiratory support. Chi-square tests, Student T tests, and logistic regression models were used to identify possible associations between spontaneous ductal closure by DOL 7 and predictor variables. Patterns of spontaneous DA closure over time were examined using Kaplan-Meier survival analysis. The DA closed spontaneously in 49% infants by DOL 7. Rates of spontaneous closure by DOL 7 differed significantly by BW strata: 67% for BW > 1000 g, 31% for BW 1000 g did not require intervention, and the DA closed spontaneously prior to discharge in 94%. In a logistic regression model, only BW > 1000 g and male gender were significantly associated with spontaneous closure by 1 week of life. The median time to spontaneous closure differed significantly between infants in the two BW strata: 7 days for > 1000 g versus 56 days for 1000 g BW is rarely indicated. In infants

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