Single cell-inductively coupled plasma-mass spectrometry (SC-ICP-MS) reveals metallic heterogeneity in a macrophage model of infectious diseases.

Single cell-inductively coupled plasma-mass spectrometry (SC-ICP-MS) offers an attractive option for rapidly measuring trace metal heterogeneity at the single cell level. Chemical fixation has been previously applied to mammalian cells prior to sample introduction so that they can be resuspended in a solution suitable for SC-ICP-MS. However, the effect of fixation on the elemental composition of suspended cells is unknown, and robust methodologies are urgently needed so that the community can measure the effects of intracellular pathogens on elemental composition of their host cells.

Expanding the boundaries of atomic spectroscopy at the single-cell level: critical review of SP-ICP-MS, LIBS and LA-ICP-MS advances for the elemental analysis of tissues and single cells.

Metals have a fundamental role in microbiology, and accurate methods are needed for their identification and quantification. The inability to assess cellular heterogeneity is considered an impediment to the successful treatment of different diseases. Unlike bulk approaches, single-cell analysis allows elemental heterogeneity across genetically identical populations to be related to specific biological events and to the effectiveness of drugs.

Fine-Tuning of PI3K/AKT Signalling by the Tumour Suppressor PTEN Is Required for Maintenance of Flight Muscle Function and Mitochondrial Integrity in Ageing Adult Drosophila melanogaster.

Insulin/insulin-like growth factor signalling (IIS), acting primarily through the PI3-kinase (PI3K)/AKT kinase signalling cassette, plays key evolutionarily conserved regulatory roles in nutrient homeostasis, growth, ageing and longevity. The dysfunction of this pathway has been linked to several age-related human diseases including cancer, Type 2 diabetes and neurodegenerative disorders. However, it remains unclear whether minor defects in IIS can independently induce the age-dependent functional decline in cells that accompany some of these diseases or whether IIS alters the sensitivity to other aberrant signalling.

Expression screening and annotation of a zebrafish myoblast cDNA library.

To analyse the myogenic transcriptome and identify novel genes involved in muscle development in an in vivo context, we have constructed a muscle specific cDNA library from GFP-expressing myoblasts purified by fluorescent activated cell sorting of transgenic zebrafish embryos. We have generated 153,428 EST sequences from this library that have been clustered into consensi, mapped to the genome assembly Zv6 and analysed for protein homology. Expression analysis of a randomly picked sample of clones using whole mount in situ hybridisation, identified 30 genes that are expressed specifically within the myotome, one third of which represent novel sequences.

Sdf1a patterns zebrafish melanophores and links the somite and melanophore pattern defects in choker mutants.

Pigment pattern formation in zebrafish presents a tractable model system for studying the morphogenesis of neural crest derivatives. Embryos mutant for choker manifest a unique pigment pattern phenotype that combines a loss of lateral stripe melanophores with an ectopic melanophore ;collar' at the head-trunk border. We find that defects in neural crest migration are largely restricted to the lateral migration pathway, affecting both xanthophores (lost) and melanophores (gained) in choker mutants.

Dietary restraint and cognitive performance in children.

Adults who attempt to restrict their dietary intake also tend to perform worse on a range of cognitive tasks. However, the extent to which this finding generalises to children has remained unclear. Following studies involving adults, we asked 44 girls (mean age = 10.

Regulatory variation at glypican-3 underlies a major growth QTL in mice.

The genetic basis of variation in complex traits remains poorly understood, and few genes underlying variation have been identified. Previous work identified a quantitative trait locus (QTL) responsible for much of the response to selection on growth in mice, effecting a change in body mass of approximately 20%. By fine-mapping, we have resolved the location of this QTL to a 660-kb region containing only two genes of known function, Gpc3 and Gpc4, and two other putative genes of unknown function.

The B-cell maturation factor Blimp-1 specifies vertebrate slow-twitch muscle fiber identity in response to Hedgehog signaling.

Vertebrate skeletal muscles comprise distinct fiber types that differ in their morphology, contractile function, mitochondrial content and metabolic properties. Recent studies identified the transcriptional coactivator PGC-1alpha as a key mediator of the physiological stimuli that modulate fiber-type plasticity in postembryonic development. Although myoblasts become fated to differentiate into distinct kinds of fibers early in development, the identities of regulatory proteins that determine embryonic fiber-type specification are still obscure.

A gene-driven approach to the identification of ENU mutants in the mouse.

The construction of parallel archives of DNA and sperm from mice mutagenized with ethylnitrosurea (ENU) represents a potentially powerful and rapid approach for identifying point mutations in any gene in the mouse genome. We provide support for this approach and report the identification of mutations in the gene (Gjb2) encoding connexin 26, using archives established from the UK ENU mutagenesis program.