Metabolic network analysis of the causes and evolution of enzyme dispensability in yeast

Under laboratory conditions 80% of yeast genes seem not to be essential for viability. This raises the question of what the mechanistic basis for dispensability is, and whether it is the result of selection for buffering or an incidental side product. Here we analyse these issues using an in silico flux model of the yeast metabolic network. The model correctly predicts the knockout fitness effects in 88% of the genes studied and in vivo fluxes. Dispensable genes might be important, but under conditions not yet examined in the laboratory. Our model indicates that this is the dominant explanation for apparent dispensability, accounting for 37-68% of dispensable genes, whereas 15-28% of them are compensated by a duplicate, and only 4-17% are buffered by metabolic network flux reorganization. For over one-half of those not important under nutrient-rich conditions, we can predict conditions when they will be important. As expected, such condition-specific genes have a more restricted phylogenetic distribution. Gene duplicates catalysing the same reaction are not more common for indispensable reactions, suggesting that the reason for their retention is not to provide compensation. Instead their presence is better explained by selection for high enzymatic flux.     

Evidence that no significant quantities ofp-amino-hyppuric acid are transported by the renal lymphatics

Zusammenfassung Bei der Bestimmung der renalen Plasmaströmung mit der Paraaminohippursäuremethode wird vorausgesetzt, dass dieser Stoff nicht durch die Lymphgefässe aus der Niere abtransportiert wird. Die Kontrolle der PAH-Konzentration im D. thoracicus während der intravenösen Infusion ergab, dass sie die Plasmakonzentration nicht signifikant überschreitet, so dass die «lymphatische PAH-Clearance» gegenüber der renalen Clearance vernachlässigt werden kann.     

An integrated approach to characterize genetic interaction networks in yeast metabolism

Although experimental and theoretical efforts have been applied to globally map genetic interactions, we still do not understand how gene-gene interactions arise from the operation of biomolecular networks. To bridge the gap between empirical and computational studies, we i, quantitatively measured genetic interactions between ～185,000 metabolic gene pairs in Saccharomyces cerevisiae, ii, superposed the data on a detailed systems biology model of metabolism and iii, introduced a machine-learning method to reconcile empirical interaction data with model predictions. We systematically investigated the relative impacts of functional modularity and metabolic flux coupling on the distribution of negative and positive genetic interactions. We also provide a mechanistic explanation for the link between the degree of genetic interaction, pleiotropy and gene dispensability. Last, we show the feasibility of automated metabolic model refinement by correcting misannotations in NAD biosynthesis and confirming them by in vivo experiments.     

Inulin clearance and renal lymph

Zusammenfassung Bei normaler Diurese ist die durch die renalen Lymphgefässen abgeführte Inulinmenge nur unbedeutend; sie beeinflusst die nach der üblichen Formel errechnete Inulinclearance nur unwesentlich.     

Bombesin promotes pancreatic growth in suckling rats

Summary The pancreatic growth promoting effect of long term administration of bombesin was investigated in suckling rats. The authors showed that bombesin given in 10 g/kg b.wt doses s.c. every 8 h for 10 days from the day of parturition stimulated pancreatic growth: it increased pancreatic weight, protein and DNA content, trypsin and amylase activity and trypsin/DNA ratio. Conclusion: Bombesin is an effective stimulator of pancreatic growth in suckling rats.     

The resistance of in situ perfused lymph trunks and lymph nodes to flow

Résumé Les ganglions lymphatiques perfusés sur place résistent à l'élévation du débit lymphatique; cette résistance peut favoriser le dévéloppement de l'dème local.