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Cell proliferation and cell growth are tightly regulated during development in order to determine both organ size and the overall size of the organism. These processes are controlled both by environmental factors and also by hormones and growth receptors. Studies in Drosophila have highlighted an insulin receptor signaling pathway highly homologous to the mammalian cascade, that plays a unique in vivo role in regulating both cell size and number in tissues. We have performed a misexpression screen, pioneered by P. Rorth, to identify novel molecules that affect cell growth when overexpressed. In this preliminary strategy over 2000 EP lines, probably representing at least 1000 different genes, were expressed under the control of wing-specific and eye-specific GAL4 drivers, and the resulting flies were screened for effects on patterning and growth of these organs. Over 100 lines exhibited a putative growth phenotype in the eye and/or in the wing. In a secondary screen these selected strains were crossed to further eye-specific and wing-specific GAL4 drivers. We are currently focusing on three expression lines from this screen which affect organ and cell size in the eye and wing. In multiple assays one of these lines acts antagonistically to PTEN, a lipid phosphatase tumor suppressor acting downstream of the insulin receptor, consistent with a possible role in positively regulating insulin receptor signaling. The insertion that drives overexpression in this line does not lie within or close to any previously characterized Drosophila genes, although database searches place a number of ESTs nearby. A detailed molecular and genetic characterization of this line is currently in progress. Two other lines also regulate growth, but their effects are more tissue specific.

Background: The Gene Ontology project is a collaborative effort to provide descriptions of gene products in a consistent and computable language, and in a species-independent manner. The Gene Ontology is designed to be applicable to all organisms but up to now has been largely under-utilized for prokaryotes and viruses, in part because of a lack of appropriate ontology terms. Background: The Gene Ontology project is a collaborative effort to provide descriptions of gene products in a consistent and computable language, and in a species-independent manner. The Gene Ontology is designed to be applicable to all organisms but up to now has been largely under-utilized for prokaryotes and viruses, in part because of a lack of appropriate ontology terms. Conclusions: Building on the microbial resources already in existence such as ViralZone, UniProtKB keywords and MeGO, this project provides an integrated ontology to describe interactions between microbial species and their hosts, with mappings to the external resources above. Housing this information within the freely-accessible Gene Ontology project allows the classes and annotation structure to be utilized by a large community of biologists and users. [ABSTRACT FROM AUTHOR]

Radiance and temperature profiles for the first time have been measured along the mesa side of Gunn diode samples, using an infrared microscope with a spatial resolution of 2.5 µm. Bulk heat generation occurs in the transit region, but measurements have shown a small amount of additional ohmic heating in the substrate layer, which will influence the maximum temperature of the device. The presented thermal measurements have been used to improve the existing thermal finite-element model of the diode. The measurements also represent an alternative method to obtain a more accurate temperature of the diode top contact without coating the sample with a high emissivity layer. [ABSTRACT FROM AUTHOR]

Abstract: Signalling by TGF-β ligands through the Smad family of transcription factors is critical for developmental patterning and growth. Disruption of this pathway has been observed in various cancers. In vertebrates, members of the Ski/Sno protein family can act as negative regulators of TGF-β signalling, interfering with the Smad machinery to inhibit the transcriptional output of this pathway. In some contexts ski/sno genes function as tumour suppressors, but they were originally identified as oncogenes, whose expression is up-regulated in many tumours. These growth regulatory effects and the normal physiological functions of Ski/Sno proteins have been proposed to result from changes in TGF-β signalling. However, this model is controversial and may be over-simplified, because recent findings indicate that Ski/Sno proteins can affect other signalling pathways. To address this issue in an in vivo context, we have analyzed the function of the Drosophila Ski/Sno orthologue, SnoN. We found that SnoN inhibits growth when overexpressed, indicating a tumour suppressor role in flies. It can act in multiple tissues to selectively and cell autonomously antagonise signalling by TGF-β ligands from both the BMP and Activin sub-families. By contrast, analysis of a snoN mutant indicates that the gene does not play a global role in TGF-β-mediated functions, but specifically inhibits TGF-β-induced wing vein formation. We propose that SnoN normally functions redundantly with other TGF-β pathway antagonists to finely adjust signalling levels, but that it can behave as an extremely potent inhibitor of TGF-β signalling when highly expressed, highlighting the significance of its deregulation in cancer cells. [Copyright &y& Elsevier]