Energy source of flagellar type III secretion

Bacterial flagella contain a specialized secretion apparatus that functions to deliver the protein subunits that form the filament and other structures to outside the membrane. This apparatus is related to the injectisome used by many gram-negative pathogens and symbionts to transfer effector proteins into host cells; in both systems this export mechanism is termed 'type III' secretion. The flagellar secretion apparatus comprises a membrane-embedded complex of about five proteins, and soluble factors, which include export-dedicated chaperones and an ATPase, FliI, that was thought to provide the energy for export. Here we show that flagellar secretion in Salmonella enterica requires the proton motive force (PMF) and does not require ATP hydrolysis by FliI. The export of several flagellar export substrates was prevented by treatment with the protonophore CCCP, with no accompanying decrease in cellular ATP levels. Weak swarming motility and rare flagella were observed in a mutant deleted for FliI and for the non-flagellar type-III secretion ATPases InvJ and SsaN. These findings show that the flagellar secretion apparatus functions as a proton-driven protein exporter and that ATP hydrolysis is not essential for type III secretion.     

Towards a proteome-scale map of the human protein-protein interaction network

Systematic mapping of protein-protein interactions, or 'interactome' mapping, was initiated in model organisms, starting with defined biological processes and then expanding to the scale of the proteome. Although far from complete, such maps have revealed global topological and dynamic features of interactome networks that relate to known biological properties, suggesting that a human interactome map will provide insight into development and disease mechanisms at a systems level. Here we describe an initial version of a proteome-scale map of human binary protein-protein interactions. Using a stringent, high-throughput yeast two-hybrid system, we tested pairwise interactions among the products of approximately 8,100 currently available Gateway-cloned open reading frames and detected approximately 2,800 interactions. This data set, called CCSB-HI1, has a verification rate of approximately 78% as revealed by an independent co-affinity purification assay, and correlates significantly with other biological attributes. The CCSB-HI1 data set increases by approximately 70% the set of available binary interactions within the tested space and reveals more than 300 new connections to over 100 disease-associated proteins. This work represents an important step towards a systematic and comprehensive human interactome project.     

Common mechanisms of nerve and blood vessel wiring

Blood vessels and nerve fibres course throughout the body in an orderly pattern, often alongside one another. Although superficially distinct, the mechanisms involved in wiring neural and vascular networks seem to share some deep similarities. The discovery of key axon guidance molecules over the past decade has shown that axons are guided to their targets by finely tuned codes of attractive and repulsive cues, and recent studies reveal that these cues also help blood vessels to navigate to their targets. Parallels have also emerged between the actions of growth factors that direct angiogenic sprouting and those that regulate axon terminal arborization.     

Analyzing market competition between Airbus and Boeing using a duo hierarchical graph model for conflict resolution

A duo hierarchical graph model for conflict resolution is developed to investigate market competition between Airbus and Boeing over aircraft sales in the Asia Pacific region. The duo hierarchical graph model, a significant extension of the graph model for conflict resolution methodology, contains two common decision makers, who take part in two related subconflicts, as well as local decision makers, who participate in only one subconflict. New stability definitions are proposed to describe forms of sanction unique to the hierarchical model. The interrelationships between stabilities in the overall graph model and in the two local models are investigated. Then the duo hierarchical graph model is applied to the competition between Airbus and Boeing in both the wide and narrow body markets in the Asia-Pacific region. The two types of Asian airlines have different operating strategies, so that the two markets constitute sub-competitions that can be modelled naturally using the duo hierarchical graph model. The stability results indicate a resolution for all decision makers that implies marketing strategies for the aircraft manufacturers and guidelines for aircraft purchase by the airlines. Thus, this model provides decision makers with a comprehensive understanding of the dynamics of the competition and guidance in identifying beneficial actions.