CHMP5 is essential for late endosome function and down-regulation of receptor signaling during mouse embryogenesis

Charged MVB protein 5 (CHMP5) is a coiled coil protein homologous to the yeast Vps60/Mos10 gene and other ESCRT-III complex members, although its precise function in either yeast or mammalian cells is unknown. We deleted the CHMP5 gene in mice, resulting in a phenotype of early embryonic lethality, reflecting defective late endosome function and dysregulation of signal transduction. Chmp5−/− cells exhibit enlarged late endosomal compartments that contain abundant internal vesicles expressing proteins that are characteristic of late endosomes and lysosomes. This is in contrast to ESCRT-III mutants in yeast, which are defective in multivesicular body (MVB) formation. The degradative capacity of Chmp5−/− cells was reduced, and undigested proteins from multiple pathways accumulated in enlarged MVBs that failed to traffic their cargo to lysosomes. Therefore, CHMP5 regulates late endosome function downstream of MVB formation, and the loss of CHMP5 enhances signal transduction by inhibiting lysosomal degradation of activated receptors

Strengthening the emergency healthcare system for mothers and children in The Gambia

A system to improve the management of emergencies during pregnancy, childbirth, infancy and childhood in a region of The Gambia (Brikama) with a population of approximately 250,000 has been developed

Effectiveness of an integrated phonological awareness approach for children with childhood apraxia of speech (CAS)

This study investigated the effectiveness of an integrated phonological awareness approach for children with childhood apraxia of speech (CAS). Change in speech, phonological awareness, letter knowledge, word decoding, and spelling skills were examined. A controlled multiple single-subject design was employed. Twelve children aged 4—7 years with CAS participated in two 6-week intervention blocks (2 sessions per week), separated by a 6-week withdrawal block. Nine children with CAS made significant gains in their production of target speech sounds and these demonstrated transfer of skills to connected speech for at least one speech target. Eight children showed significant gains in at least one target phoneme awareness skill, and these children demonstrated transfer of skills to novel phoneme awareness tasks. As a group the children with CAS demonstrated improvement in phonological awareness, letter knowledge, word decoding, and spelling ability. An integrated phonological awareness programme was an effective method of simultaneously improving speech, phoneme awareness, word decoding, and spelling ability for some children with CAS