Cancer gene discovery in solid tumours using transposon-based somatic mutagenesis in the mouse

Retroviruses, acting as somatic cell insertional mutagens, have been widely used to identify cancer genes in the haematopoietic system and mammary gland. An insertional mutagen for use in other mouse somatic cells would facilitate the identification of genes involved in tumour formation in a wider variety of tissues. Here we report the ability of the Sleeping Beauty transposon to act as a somatic insertional mutagen to identify genes involved in solid tumour formation. A Sleeping Beauty transposon, engineered to elicit loss-of-function or gain-of-function mutations, transposed in all somatic tissues tested and accelerated tumour formation in mice predisposed to cancer. Cloning transposon insertion sites from these tumours revealed the presence of common integration sites, at known and candidate cancer genes, similar to those observed in retroviral mutagenesis screens. Sleeping Beauty is a new tool for unbiased, forward genetic screens for cancer genes in vivo.     

Proximate humid and dry regions in Jupiter's atmosphere indicate complex local meteorology

Models of Jupiter's formation and structure predict that its atmosphere is enriched in oxygen, relative to the Sun, and that consequently water clouds should be present globally near the 5-bar pressure level. Past attempts to confirm these predictions have led to contradictory results; in particular, the Galileo probe revealed a very dry atmosphere at the entry site, with no significant clouds at depths exceeding the 2-bar level. Although the entry site was known to be relatively cloud-free, the contrast between the observed local dryness and the expected global wetness was surprising. Here we analyse near-infrared (around 5 microm) observations of Jupiter, a spectral region that can reveal the water vapour abundance and vertical cloud structure in the troposphere. We find that humid and extremely dry regions exist in close proximity, and that some humid regions are spatially correlated with bright convective clouds extending from the deep water clouds to the visible atmosphere.     

A comparison between the free grafting of sliced and intact muscles in the rat-1.

Transverse slicing is a new technique whereby a mammalian muscle can be freely grafted with success. This method eliminates contamination of the early graft by surviving muscle fibres and allows one to measure the development of contractile properties on a uniform population of regenerating muscle fibres.?IOAuthor     

Attraction of the male house fly to cuticular hydrocarbons and feces of several other dipteran species

Zusammenfassung Männchen vonMusca domestica werden von Kohlenwasserstoffextrakten aus der Cuticula weiblicherMusca domestica, M. autumnalis undHaematobia irritan angelockt (gleiche oder ähnliche Pheromone), nicht aber von entsprechenden Extrakten ausStomoxys calitrans, Glossina morsitans, G. austeni, Fannia canicularis undCochliomyia hominivorax.

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The authors thankDr. P. A. Langley, University of Bristol, for his geneous aid in providing cuticular washes and feces of tsetse flies;Dr. C. M. Jones, USDA, for face fly samples;Dr. R. L. Harris, USDA, for horn fly samples;Dr. B. G. Hightower and R. R. Grabbe, USDA, for screwworm samples andDr. W. M. Rogoff, USDA, for little house fly samples.     

Mutations in the gene encoding lecithin retinol acyltransferase are associated with early-onset severe retinal dystrophy

The chromophore of the visual pigments, 11-cis retinal, is derived from vitamin A (all-trans retinol) through a series of reactions that take place in retinal pigment epithelium (RPE); (ref. 1). The first of these reactions is catalyzed by lecithin retinol acyltransferase (LRAT); (ref. 2). We screened 267 retinal dystrophy patients for mutations in LRAT and identified disease-associated mutations (S175R and 396delAA) in three individuals with severe, early-onset disease. We showed that the S175R mutant has no acyltransferase activity in transfected COS-7 cells. Our findings highlight the importance of genetic defects in vitamin A metabolism as causes of retinal dystrophies and extend prospects for retinoid replacement therapy in this group of diseases.     

Mammalian SWI/SNF complexes promote MyoD-mediated muscle differentiation

Mammalian SWI/SNF complexes are ATP-dependent chromatin remodeling enzymes that have been implicated in the regulation of gene expression, cell-cycle control and oncogenesis. MyoD is a muscle-specific regulator able to induce myogenesis in numerous cell types. To ascertain the requirement for chromatin remodeling enzymes in cellular differentiation processes, we examined MyoD-mediated induction of muscle differentiation in fibroblasts expressing dominant-negative versions of the human brahma-related gene-1 (BRG1) or human brahma (BRM), the ATPase subunits of two distinct SWI/SNF enzymes. We find that induction of the myogenic phenotype is completely abrogated in the presence of the mutant enzymes. We further demonstrate that failure to induce muscle-specific gene expression correlates with inhibition of chromatin remodeling in the promoter region of an endogenous muscle-specific gene. Our results demonstrate that SWI/SNF enzymes promote MyoD-mediated muscle differentiation and indicate that these enzymes function by altering chromatin structure in promoter regions of endogenous, differentiation-specific loci.