Starting the invasion pathway: the interaction between source populations and human transport vectors

Human transport hubs, such as shipping ports, airports and mail centers are important foci for the spread of non-indigenous species. High relative abundance in a transport hub has been proposed as a correlate of invasion success, since abundant species are thought more likely to colonize vectors and to be transported more frequently. We here evaluate the relative importance of vector characteristics and local source assemblages in determining the pool of species that is transported by hull fouling on recreational boats. We compared the resident fouling communities of three recreational boat harbors in Australia with the assemblages on the hulls of boats that travel between them. We used data on the recent travel and maintenance history of the boats to evaluate correlates of transport probability and the potential for intra-coastal spread of fouling organisms. Invertebrate assemblages on heavily fouled vessels reflected the composition of biotic assemblages within the marina in which they were moored, but by itself, relative abundance in the source port was not a reliable predictor of transport probability. More important was the age of the antifouling paint on the vessels’ hulls, which acted selectively on some groups of organisms. Movements of vessels were characterized by “fidelity” (vessels remaining close to homeport) interspersed with “promiscuity” (vessels traveling to a diverse pool of destinations). In an infested harbor, measures taken to increase the resistance of vectors to colonization by the invader should be effective in slowing the rate of spread to other locations, by decreasing the overall frequency of transport.     

Interactomics: toward protein function and regulation

Protein–protein interactions are central to all cellular processes. Understanding of protein–protein interactions is therefore fundamental for many areas of biochemical and biomedical research and will facilitate an understanding of the cell process-regulating machinery, disease causative mechanisms, biomarkers, drug target discovery and drug development. In this review, we summarize methods for populating and analyzing the interactome, highlighting their advantages and disadvantages. Applications of interactomics in both the biochemical and clinical arenas are presented, illustrating important recent advances in the field.     

Structure networks of E. coli glutaminyl-tRNA synthetase: effects of ligand binding

It is well known that proteins undergo backbone as well as side chain conformational changes upon ligand binding, which is not necessarily confined to the active site. Both the local and the global conformational changes brought out by ligand-binding have been extensively studied earlier. However, the global changes have been reported mainly at the protein backbone level. Here we present a method that explicitly takes into account the side chain interactions, yet providing a global view of the ligand-induced conformational changes. This is achieved through the analysis of Protein Structure Networks (PSN), constructed from the noncovalent side chain interactions in the protein. Here, E. coli Glutaminyl-tRNA synthetase (GlnRS) in the ligand-free and different ligand-bound states is used as a case study to assess the effect of binding of tRNA, ATP, and the amino acid Gln to GlnRS. The PSNs are constructed on the basis of the strength of noncovalent interactions existing between the side chains of amino acids. The parameters like the size of the largest cluster, edge to node ratio, and the total number of hubs are used to quantitatively assess the structure network changes. These network parameters have effectively captured the ligand-induced structural changes at a global structure network level. Hubs, the highly connected amino acids, are also identified from these networks. Specifically, we are able to characterize different types of hubs based on the comparison of structure networks of the GlnRS system. The differences in the structure networks in both the presence and the absence of the ligands are reflected in these hubs. For instance, the characterization of hubs that are present in both the ligand-free and all the ligand-bound GlnRS (the invariant hubs) might implicate their role in structural integrity. On the other hand, identification of hubs unique to a particular ligand-bound structure (the exclusive hubs) not only highlights the structural differences mediated by ligand-binding at the structure network level, but also highlights significance of these amino acids hubs in binding to the ligand and catalyzing the biochemical function. Further, the hubs identified from this study could be ideal targets for mutational studies to ascertain the ligand-induced structure-function relationships in E. coli GlnRS. The formalism used in this study is simple and can be applied to other protein-ligands in general to understand the allosteric changes mediated by the binding of ligands.     

Global Regulation of a Differentiation MAPK Pathway in Yeast

Cell differentiation requires different pathways to act in concert to produce a specialized cell type. The budding yeast Saccharomyces cerevisiae undergoes filamentous growth in response to nutrient limitation. Differentiation to the filamentous cell type requires multiple signaling pathways, including a mitogen-activated protein kinase (MAPK) pathway. To identify new regulators of the filamentous growth MAPK pathway, a genetic screen was performed with a collection of 4072 nonessential deletion mutants constructed in the filamentous (Σ1278b) strain background. The screen, in combination with directed gene-deletion analysis, uncovered 97 new regulators of the filamentous growth MAPK pathway comprising 40% of the major regulators of filamentous growth. Functional classification extended known connections to the pathway and identified new connections. One function for the extensive regulatory network was to adjust the activity of the filamentous growth MAPK pathway to the activity of other pathways that regulate the response. In support of this idea, an unregulated filamentous growth MAPK pathway led to an uncoordinated response. Many of the pathways that regulate filamentous growth also regulated each other’s targets, which brings to light an integrated signaling network that regulates the differentiation response. The regulatory network characterized here provides a template for understanding MAPK-dependent differentiation that may extend to other systems, including fungal pathogens and metazoans.     

Unravelling the global invasion routes of a worldwide invader,the red swamp crayfish (Procambarus clarkii)

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The role of disorder in interaction networks: a structural analysis

Recent studies have emphasized the value of including structural information into the topological analysis of protein networks. Here, we utilized structural information to investigate the role of intrinsic disorder in these networks. Hub proteins tend to be more disordered than other proteins (i.e. the proteome average); however, we find this only true for those with one or two binding interfaces (‘single’‐interface hubs). In contrast, the distribution of disordered residues in multi‐interface hubs is indistinguishable from the overall proteome. Surprisingly, we find that the binding interfaces in single‐interface hubs are highly structured, as is the case for multi‐interface hubs. However, the binding partners of single‐interface hubs tend to have a higher level of disorder than the proteome average, suggesting that their binding promiscuity is related to the disorder of their binding partners. In turn, the higher level of disorder of single‐interface hubs can be partly explained by their tendency to bind to each other in a cascade. A good illustration of this trend can be found in signaling pathways and, more specifically, in kinase cascades. Finally, our findings have implications for the current controversy related to party and date‐hubs.