The 5'-3' exoribonuclease pacman is required for epithelial sheet sealing in Drosophila and genetically interacts with the phosphatase puckered.

BACKGROUND INFORMATION: Ribonucleases have been well studied in yeast and bacteria, but their biological significance to developmental processes in multicellular organisms is not well understood. However, there is increasing evidence that specific timed transcript degradation is critical for regulation of many cellular processes, including translational repression, nonsense-mediated decay and RNA interference. The Drosophila gene pacman is highly homologous to the major yeast exoribonuclease XRN1 and is the only known cytoplasmic 5'-3' exoribonuclease in eukaryotes. To determine the effects of this exoribonuclease in development we have constructed a number of mutations in pacman by P-element excision and characterized the resulting phenotypes. RESULTS: Mutations in pacman resulted in flies with a number of specific phenotypes, such as low viability, dull wings, crooked legs, failure of correct dorsal/thorax closure and defects in wound healing. The epithelial sheet movement involved in dorsal/thorax closure is a conserved morphogenetic process which is similar to that of hind-brain closure in vertebrates and wound healing in humans. As the JNK (c-Jun N-terminal kinase) signalling pathway is known to be involved in dorsal/thorax closure and wound healing, we tested whether pacman affects JNK signalling. Our experiments demonstrate that pacman genetically interacts with puckered, a phosphatase that negatively regulates the JNK signalling pathway. CONCLUSIONS: These results reveal that the 5'-3' exoribonuclease pacman is required for a critical aspect of epithelial sheet sealing in Drosophila. Since these mutations result in specific phenotypes, our data suggest that the exoribonuclease Pacman targets a specific subset of mRNAs involved in this process. One of these targets could be a member of the JNK signalling pathway, although it is possible that a parallel pathway may instead be affected. The exoribonuclease pacman is highly conserved in all eukaryotes, therefore it is likely that it is involved in similar morphological processes, such as wound healing in human cells.

Rising incidence of type 2 diabetes in children in the U.K.

OBJECTIVE: To estimate the incidence of type 2 diabetes in children <17 years of age and to investigate the relationship of diabetes with increasing childhood obesity in the U.K. and the Republic of Ireland (ROI). RESEARCH DESIGN AND METHODS: Active monthly reporting of cases by consultant pediatricians occurred through the framework of the British Pediatric Surveillance Unit, with additional reports from specialist diabetes nurses. All children <17 years of age and diagnosed by their clinician as having non-type 1 diabetes from 1 October 2004 to 31 October 2005 were included. RESULTS: A total of 168 confirmed cases of non-type 1 diabetes were reported, resulting in a national incidence (excluding the ROI) of 1.3 x 100,000(-1) x year(-1). Of these, 40% were diagnosed with type 2 diabetes giving a minimum incidence of 0.53 x 100,000(-1) x year(-1). Children of ethnic minorities were greatly overrepresented, with those of black and South-Asian origin (England data only) having an incidence of 3.9 and 1.25 x 100,000(-1) x year(-1), respectively, compared with 0.35 x 100,000(-1) x year(-1) in those defined as white. Of those diagnosed with type 2 diabetes, 95% were overweight and 83% obese according to International Obesity Task Force guidelines. Eighty-four percent had a family history of type 2 diabetes. CONCLUSIONS: Type 2 diabetes is still less common than type 1 diabetes in U.K. children. However, compared with previous prevalence data, the frequency of type 2 diabetes appears to be increasing. Incidence among ethnic minorities is far higher than in whites, as previously described in the U.S. Increased adiposity and family history of type 2 diabetes were strongly associated with the diagnosis of type 2 diabetes in U.K. children.