Methylation of the Sterol Nucleus by STRM-1 Regulates Dauer Larva Formation in Caenorhabditis elegans

In response to pheromone(s), Caenorhabditis elegans interrupts its reproductive life cycle and enters diapause as a stress-resistant dauer larva. This decision is governed by a complex system of neuronal and hormonal regulation. All the signals converge onto the nuclear hormone receptor DAF-12. A sterol-derived hormone, dafachronic acid (DA), supports reproductive development by binding to DAF-12 and inhibiting its dauer-promoting activity. Here, we identify a methyltransferase, STRM-1, that modulates DA levels and thus dauer formation. By modifying the substrates that are used for the synthesis of DA, STRM-1 can reduce the amount of hormone produced. Loss of STRM-1 function leads to elevated levels of DA and inefficient dauer formation. Sterol methylation was not previously recognized as a mechanism for regulating hormone activity. Moreover, the C-4 sterol nucleus methylation catalyzed by STRM-1 is unique to nematodes and thus could be a target for therapeutic strategies against parasitic nematode infections

Safety of endoscopic retrograde cholangiopancreatography in the pediatric population: a multicenter study

INTRODUCTION: The aims of this retrospective multicenter study were to assess the technical success and adverse events of endoscopic retrograde cholangiopancreatography (ERCP) procedures in children in French and Belgian centers. METHODS: All children aged 1 day to 17 years who underwent ERCP between January 2008 and March 2019 in 15 tertiary care hospitals were retrospectively included. RESULTS: 271 children underwent 470 ERCP procedures. Clinical long-term follow-up was available for 72 % of our patients (340/470 procedures). The median age at intervention was 10.9 years. ERCP was therapeutic in 90 % (423/470) and diagnostic in cases of neonatal cholestasis in 10 % of the patients. The most common biliary indication was choledocholithiasis; the most common pancreatic indication was chronic pancreatitis. Biliary cannulation was successful in 92 % of cases (270/294); pancreatic cannulation in 96 % of cases (169/176); and planned therapeutic procedures in 92 % of cases (388/423). The overall complication rate was 19 % (65/340). The most common complication was post-ERCP pancreatitis (PEP) in 12 % of cases (40/340) and sepsis in 5 % (18/340). On univariate analyses, pancreatic stent removal was protective against PEP (odds ratio [OR] 0.1, 95 % confidence interval [CI] 0.01 - 0.75; P = 0.03), and sepsis was associated with history of liver transplantation (OR 7.27, 95 %CI 1.7 - 31.05; P = 0.01). Five patients had post-ERCP hemorrhage and two had intestinal perforation. All complications were managed with supportive medical care. There was no procedure-related mortality. CONCLUSION: Our cohort demonstrates that ERCP can be performed safely with high success rates in many pancreaticobiliary diseases of children. The rate of adverse events was similar to that in previous reports