The synthesis of substituted amino[2.2]paracyclophanes.

Two methodologies for the formation of substituted amino[2.2]paracyclophane derivatives were developed. The first involves the direct amination of bromo[2.

Quality improvement project to reduce paediatric prescribing errors in a teaching hospital.

A quality improvement project to reduce paediatric prescribing errors was carried out in a London teaching hospital between June 2013 and March 2014. It involved paediatric medical and surgical wards and a paediatric intensive care unit. A multi professional team of 'prescribing champions' was formed.

'It's a matter of your personality more than anything else'.

The impact on full-time carers of children with intellectual disabilities who exhibit challenging behaviour has been well researched (e.g. Lach et al.

A Gal4/UAS system for conditional transgene expression in rhombomere 4 of the zebrafish hindbrain.

Background: The zebrafish is well established as a model organism for the study of vertebrate embryogenesis, but transgenic lines enabling restricted gene expression are still lacking for many tissues.

Results: We first generated the hoxb1a(β-globin):eGFP(um8) line that expresses eGFP in hindbrain rhombomere 4 (r4), as well as in facial motor neurons migrating caudally from r4. Second, we generated the hoxb1a(β-globin) Gal4VP16(um60) line to express the exogenous Gal4VP16 transcription factor in r4.

Myogenic microRNA expression requires ATP-dependent chromatin remodeling enzyme function.

Knockdown of the Brg1 ATPase subunit of SWI/SNF chromatin remodeling enzymes in developing zebrafish caused stunted tail formation and altered sarcomeric actin organization, which phenocopies the loss of the microRNA processing enzyme Dicer, or the knockdown of myogenic microRNAs. Furthermore, myogenic microRNA expression and differentiation was blocked in Brg1 conditional myoblasts differentiated ex vivo. The binding of Brg1 upstream of myogenic microRNA sequences correlated with MyoD binding and accessible chromatin structure in satellite cells and myofibers, and it was required for chromatin accessibility and microRNA expression in a tissue culture model for myogenesis.

Evidence for a role of vertebrate Disp1 in long-range Shh signaling.

Dispatched 1 (Disp1) encodes a twelve transmembrane domain protein that is required for long-range sonic hedgehog (Shh) signaling. Inhibition of Disp1 function, both by RNAi or dominant-negative constructs, prevents secretion and results in the accumulation of Shh in source cells. Measuring the Shh response in neuralized embryoid bodies (EBs) derived from embryonic stem (ES) cells, with or without Disp1 function, demonstrates an additional role for Disp1 in cells transporting Shh.

Maternal and zygotic aldh1a2 activity is required for pancreas development in zebrafish.

We have isolated and characterized a novel zebrafish pancreas mutant. Mutant embryos lack expression of isl1 and sst in the endocrine pancreas, but retain isl1 expression in the CNS. Non-endocrine endodermal gene expression is less affected in the mutant, with varying degrees of residual expression observed for pdx1, carbA, hhex, prox1, sid4, transferrin and ifabp.

Modulation of morphogenesis by noncanonical Wnt signaling requires ATF/CREB family-mediated transcriptional activation of TGFbeta2.

Transcriptional readout downstream of canonical Wnt signaling is known to be mediated by beta-catenin activation of well-described targets, but potential transcriptional readout in response to noncanonical Wnt signaling remains poorly understood. Here, we define a transcriptional pathway important in noncanonical Wnt signaling. We have found that Wnt11 is a direct target of a canonical beta-catenin pathway in developing heart and that Wnt11 mutants show cardiac outflow tract defects.

TALE-family homeodomain proteins regulate endodermal sonic hedgehog expression and pattern the anterior endoderm.

sonic hedgehog (shh) is expressed in anterior endoderm, where it is required to repress pancreas gene expression and to pattern the endoderm, but the pathway controlling endodermal shh expression is unclear. We find that expression of meis3, a TALE class homeodomain gene, coincides with shh expression in the endoderm of zebrafish embryos. Using a dominant negative construct or anti-sense morpholino oligos (MOs) to disrupt meis3 function, we observe ectopic insulin expression in anterior endoderm.

The use of interferon beta in relapsing-remitting multiple sclerosis.

The use of interferon beta-1a to treat multiple sclerosis in a child of 7 years of age is discussed. To date, there is only one other published report of the use of interferon beta in a child as young as this. One year after commencing treatment she had shown significant clinical improvement, with a marked reduction in number of relapses.

A zebrafish unc-45-related gene expressed during muscle development.

We report the isolation and expression pattern of zebrafish unc45r, a gene related to Caenorhabditis elegans unc-45. UNC-45 is a muscle-specific protein thought to interact with myosin and promote the assembly of muscle thick filaments during C. elegans development.