sRNA methylase activity of embryonic liver

Résumé Utilisant SAM-¹⁴CH₃ il a été démontré que le foie foetal a plus d'activité de sRNA methylase que le foie adulte.

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This investigation was supported in part by an allocation from a Public Health Service General Research Support Grant No. SO 1 FR-05545-03, and an American Cancer Society Grant No. IN 19F to The Jackson Laboratory, Bar Harbor, Maine, and by Public Health Service Research Grants No. HD-01496 from the National Institute of Child Health and Human Development and No. FR-00251 from the Division of Research Facilities and Resources.     

IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice

Studies in invertebrates have led to the identification of a number of genes that regulate lifespan, some of which encode components of the insulin or insulin-like signalling pathways. Examples include the related tyrosine kinase receptors InR (Drosophila melanogaster) and DAF-2 (Caenorhabditis elegans) that are homologues of the mammalian insulin-like growth factor type 1 receptor (IGF-1R). To investigate whether IGF-1R also controls longevity in mammals, we inactivated the IGF-1R gene in mice (Igf1r). Here, using heterozygous knockout mice because null mutants are not viable, we report that Igf1r(+/-) mice live on average 26% longer than their wild-type littermates (P < 0.02). Female Igf1r(+/-) mice live 33% longer than wild-type females (P < 0.001), whereas the equivalent male mice show an increase in lifespan of 16%, which is not statistically significant. Long-lived Igf1r(+/-) mice do not develop dwarfism, their energy metabolism is normal, and their nutrient uptake, physical activity, fertility and reproduction are unaffected. The Igf1r(+/-) mice display greater resistance to oxidative stress, a known determinant of ageing. These results indicate that the IGF-1 receptor may be a central regulator of mammalian lifespan.     

Transcriptome analysis of the acoelomate human parasite Schistosoma mansoni

Schistosoma mansoni is the primary causative agent of schistosomiasis, which affects 200 million individuals in 74 countries. We generated 163,000 expressed-sequence tags (ESTs) from normalized cDNA libraries from six selected developmental stages of the parasite, resulting in 31,000 assembled sequences and 92% sampling of an estimated 14,000 gene complement. By analyzing automated Gene Ontology assignments, we provide a detailed view of important S. mansoni biological systems, including characterization of metazoa-specific and eukarya-conserved genes. Phylogenetic analysis suggests an early divergence from other metazoa. The data set provides insights into the molecular mechanisms of tissue organization, development, signaling, sexual dimorphism, host interactions and immune evasion and identifies novel proteins to be investigated as vaccine candidates and potential drug targets.     

Staphylocoagulase is a prototype for the mechanism of cofactor-induced zymogen activation

Many bacterial pathogens secrete proteins that activate host trypsinogen-like enzyme precursors, most notably the proenzymes of the blood coagulation and fibrinolysis systems. Staphylococcus aureus, an important human pathogen implicated in sepsis and endocarditis, secretes the cofactor staphylocoagulase, which activates prothrombin, without the usual proteolytic cleavages, to directly initiate blood clotting. Here we present the 2.2 A crystal structures of human alpha-thrombin and prethrombin-2 bound to a fully active staphylocoagulase variant. The cofactor consists of two domains, each with three-helix bundles; this is a novel fold that is distinct from known serine proteinase activators, particularly the streptococcal plasminogen activator streptokinase. The staphylocoagulase fold is conserved in other bacterial plasma-protein-binding factors and extracellular-matrix-binding factors. Kinetic studies confirm the importance of isoleucine 1 and valine 2 at the amino terminus of staphylocoagulase for zymogen activation. In addition to making contacts with the 148 loop and (pro)exosite I of prethrombin-2, staphylocoagulase inserts its N-terminal peptide into the activation pocket of bound prethrombin-2, allosterically inducing functional catalytic machinery. These investigations demonstrate unambiguously the validity of the zymogen-activation mechanism known as 'molecular sexuality'.     

Isaac Newton and Augustan Anglo-Latin poetry

Although many historians of science acknowledge the extent to which Greek and Roman ideals framed eighteenth-century thought, many classical references in the texts they study remain obscure. Poems played an important role not only in spreading ideas about natural philosophy, but also in changing people’s perceptions of its value; they contributed to Newton’s swelling reputation as an English hero. By writing about Latin poetry, we focus on the intersection of two literary genres that were significant for eighteenth-century natural philosophy, but seem alien to modern science. We classify Augustan Latinate scientific poetry by considering the audiences for whom the poems were intended. We distinguish three broad categories. One type of poetry was circulated amongst gentlemanly scholars (we look particularly at Tripos verses, and laments for Queen Caroline). A second group comprised poetry written specifically to promote or criticise Newton and his books, particularly the Principia (we look at versions of Pope’s epitaph, and Halley’s Lucretian poem). After Newton’s death, a third type of poetry became increasingly significant, included in collections of poems rather than in texts of natural philosophy. Overall, we show how the classical past was vital for creating the scientific future.     

Biosynthesis of phosphatidylethanolamine from CDP-ethanolamine by the Golgi complex of rat liver in vitro

Summary A Golgi-rich fraction from rat liver has been shown to synthesize phosphatidylethanolamine from CDP-ethanolamine in vitro. The implications of the existence of such a pathway for the membrane flow hypothesis are discussed.Acknowledgments. This study was supported by the Medical Research Council of Canada.     

The effects of tryptophol on immune responses and its implications toward trypanosome-induced immunosuppression

Summary Daily administrations of tryptophol to laboratory rodents resulted in significantly depressed antibody production to heterologous red blood cell challenge, but did not alter cellular-mediated responses to oxazalone. These results suggest that trypanosome-produced tryptophol may account for the immunodepression observed during trypanosomiasis.