Ptch2/Gas1 and Ptch1/Boc differentially regulate Hedgehog signalling in murine primordial germ cell migration.

Gas1 and Boc/Cdon act as co-receptors in the vertebrate Hedgehog signalling pathway, but the nature of their interaction with the primary Ptch1/2 receptors remains unclear. Here we demonstrate, using primordial germ cell migration in mouse as a developmental model, that specific hetero-complexes of Ptch2/Gas1 and Ptch1/Boc mediate the process of Smo de-repression with different kinetics, through distinct modes of Hedgehog ligand reception. Moreover, Ptch2-mediated Hedgehog signalling induces the phosphorylation of Creb and Src proteins in parallel to Gli induction, identifying a previously unknown Ptch2-specific signal pathway. We propose that although Ptch1 and Ptch2 functionally overlap in the sequestration of Smo, the spatiotemporal expression of Boc and Gas1 may determine the outcome of Hedgehog signalling through compartmentalisation and modulation of Smo-downstream signalling. Our study identifies the existence of a divergent Hedgehog signal pathway mediated by Ptch2 and provides a mechanism for differential interpretation of Hedgehog signalling in the germ cell niche

Home treatment of 'malaria' in children in rural Gambia is uncommon.

Home treatment with antimalarials is a common practice in many countries, and may save lives by ensuring that more malaria cases receive prompt treatment. Through retrospective surveys we found that home treatment of young children with antimalarials was uncommon in rural Gambia. Few families kept medicines in the home in case of illness, 28% kept paracetamol and only 8% kept chloroquine. Less than 10% of cases of childhood 'malaria' had been treated with chloroquine at home, and 69% of those giving home medication did not know the correct dosage for a child. The most common course of treatment was the use of paracetamol and/or tepid sponging to reduce fever, before the child was taken to a government health facility. Treating a child with antimalarials at home was more costly than other forms of treatment. The low cost associated with the use of health services for children and the limited availability of antimalarials outside major towns contribute to the high use of government health services. This shows that that home treatment cannot be assumed to be the predominant mode of malaria treatment throughout Africa, and highlights the need for country-specific policies based on accurate local knowledge of treatment practices in both rural and urban areas

The makings of maleness: towards an integrated view of male sexual development

As the mammalian embryo develops, it must engage one of the two distinct programmes of gene activity, morphogenesis and organogenesis that characterize males and females. In males, sexual development hinges on testis determination and differentiation, but also involves many coordinated transcriptional, signalling and endocrine networks that underpin the masculinization of other organs and tissues, including the brain. Here we bring together current knowledge about these networks, identify gaps in the overall picture, and highlight the known defects that lead to disorders of male sexual development