Recommendations of the 2006 Human Variome Project meeting

Lists of variations in genomic DNA and their effects have been kept for some time and have been used in diagnostics and research. Although these lists have been carefully gathered and curated, there has been little standardization and coordination, complicating their use. Given the myriad possible variations in the estimated 24,000 genes in the human genome, it would be useful to have standard criteria for databases of variation. Incomplete collection and ascertainment of variants demonstrates a need for a universally accessible system. These and other problems led to the World Heath Organization-cosponsored meeting on June 20-23, 2006 in Melbourne, Australia, which launched the Human Variome Project. This meeting addressed all areas of human genetics relevant to collection of information on variation and its effects. Members of each of eight sessions (the clinic and phenotype, the diagnostic laboratory, the research laboratory, curation and collection, informatics, relevance to the emerging world, integration and federation and funding and sustainability) developed a number of recommendations that were then organized into a total of 96 recommendations to act as a foundation for future work worldwide. Here we summarize the background of the project, the meeting and its recommendations.     

Fringe forms a complex with Notch

The Fringe protein of Drosophila and its vertebrate homologues function in boundary determination during pattern formation. Fringe has been proposed to inhibit Serrate-Notch signalling but to potentiate Delta-Notch signalling. Here we show that Fringe and Notch form a complex through both the Lin-Notch repeats and the epidermal growth factor repeats 22-36 (EGF22-36) of Notch when they are co-expressed. The Abruptex59b (Ax59b) and AxM1 mutations, which are caused by missense mutations in EGF repeats 24 and 25, respectively, abolish the Fringe-Notch interaction through EGF22-36, whereas the l(1)N(B) mutation in the third Lin-Notch repeat of Notch abolishes the interaction through Lin-Notch repeats. Ax mutations also greatly affect the Notch response to ectopic Fringe in vivo. Results from in vitro protein mixing experiments and subcellular colocalization experiments indicate that the Fringe-Notch complex may form before their secretion. These findings explain how Fringe acts cell-autonomously to modulate the ligand preference of Notch and why the Fringe-Notch relationship is conserved between phyla and in the development of very diverse structures.     

Renal lesions induced by the simultaneous administration of angiotensin and hexadimethrine bromide

Zusammenfassung Einmalige Verabreichung von Angiotensin oder Hexadimethrin-bromid verursacht bei der Ratte keine signifikante Schädigung der Nierenrinde. Wird zuerst Angiotensin und wenige Minuten später Hexadimethrin-bromid injiziert, so kommt es zu Nierenrindeninfarkten, fokalen glomerulären und tubulären Nekrosen.     

Identification and processing of proglucagon in pancreatic islets.

Immunoprecipitation and tryptic peptide analysis of newly synthesized proteins from rat islets have identified an 18,000 molecular weight (MW) protein as proglucagon. Conversion of this precursor was kinetically similar to the conversion of proinsulin and resulted in the formation of both pancreatic glucagon and a 10,000-MW protein lacking this hormonal sequence.     

History and status of the Franklin's Gull on Malheur National Wildlife Refuge, Oregon

Franklin's Gulls first arrived in southeast Oregon in 1943, but the first nest was not located until 1948. From 1949 to 1964 gull numbers showed annual fluctuations. An increase began in 1965 and continued through 1980. By 1980 an estimated 2500 Franklin's Gulls were nesting on Malheur National Wildlife Refuge, Harney County, Oregon. The species arrives in April and nesting begins by 1 June. Average nest and egg measurements were similar to those from other areas within the species range.