Reconstructing Mesoscale Network Structures

When facing the problem of reconstructing complex mesoscale network structures, it is generally believed that models encoding the nodes organization into modules must be employed. The present paper focuses on two block structures that characterize the empirical mesoscale organization of many real-world networks, i.e., the bow-tie and the core-periphery ones, with the aim of quantifying the minimal amount of topological information that needs to be enforced in order to reproduce the topological details of the former. Our analysis shows that constraining the network degree sequences is often enough to reproduce such structures, as confirmed by model selection criteria as AIC or BIC. As a byproduct, our paper enriches the toolbox for the analysis of bipartite networks, still far from being complete: both the bow-tie and the core-periphery structure, in fact, partition the networks into asymmetric blocks characterized by binary, directed connections, thus calling for the extension of a recently proposed method to randomize undirected, bipartite networks to the directed case

The focal adhesion-associated proteins DOCK5 and GIT2 comprise a rheostat in control of epithelial invasion

DOCK proteins are guanine nucleotide exchange factors for Rac and Cdc42 GTPases. DOCK1 is the founding member of the family and acts downstream of integrins via the canonical Crk-p130Cas complex to activate Rac GTPases in numerous contexts. In contrast, DOCK5, which possesses the greatest similarity to DOCK1, remains sparingly studied. Here we establish that DOCK5 has a non-redundant role in regulating motile and invasive capacities of epithelial cells. DOCK1 is constitutively associated with sites of integrin attachment termed focal adhesions (FAs). In contrast, we demonstrate that DOCK5 recruitment to FAs in Hela cells is restricted by GIT2, an established regulator of FA signaling. We determine that GIT2 is targeted to FAs in response to Rho-ROCK signaling and actomyosin contractility. Accordingly, inhibition of ROCK activity or MLC function promotes enrichment of DOCK5 in membrane protrusions and nascent cell–substratum adhesions. We further demonstrate that GIT2 inhibits the interaction of DOCK5 with Crk. Moreover, we show that depletion of GIT2 promotes DOCK5-dependent activation of the Crk-p130Cas signaling cascade to promote Rac1-mediated lamellipodial protrusion and FA turnover. The antagonism between GIT2 and DOCK5 extends to non-transformed MCF10A mammary epithelial cells, with DOCK5 ‘dialing-up' and GIT2 ‘dialing-down' invasiveness. Finally, we determine that DOCK5 inhibition attenuates invasion and metastasis of MDA-MB-231 cells and prolongs life span of mice injected with these cells. Collectively, our work identifies DOCK5 as a key regulator of epithelial invasion and metastasis, and demonstrates that suppression of DOCK5 by GIT2 represents a previously unappreciated mechanism for coordination of Rho and Rac GTPases

Reconstructing Mesoscale Network Structures

This is the final version. Available from Hindawi via the DOI in this record.World Trade Web data that support the findings of this study are openly available at the UN Comtrade Database (http://comtrade.un.org/). Dutch interbank exposures data are not publicly available due to privacy restrictions.When facing the problem of reconstructing complex mesoscale network structures, it is generally believed that models encoding the nodes organization into modules must be employed. The present paper focuses on two block structures that characterize the empirical mesoscale organization of many real-world networks, i.e., the bow-tie and the core-periphery ones, with the aim of quantifying the minimal amount of topological information that needs to be enforced in order to reproduce the topological details of the former. Our analysis shows that constraining the network degree sequences is often enough to reproduce such structures, as confirmed by model selection criteria as AIC or BIC. As a byproduct, our paper enriches the toolbox for the analysis of bipartite networks, still far from being complete: both the bow-tie and the core-periphery structure, in fact, partition the networks into asymmetric blocks characterized by binary, directed connections, thus calling for the extension of a recently proposed method to randomize undirected, bipartite networks to the directed case.EUEUEUEUEUNewton International FellowshipThe Royal SocietyThe British AcademyAcademy of Medical Science

Breaking Traditions:An Isotopic Study on the Changing Funerary Practices in the Dutch Iron Age (800-12 bc)

Urnfields in the Dutch river area were replaced by cemeteries with a mixture of cremation and inhumation graves around the sixth century bc. This study provides the first biogeochemical evidence that the Iron Age communities were heterogeneous in terms of geological origins. The high percentage of non-locally born individuals (~48%) supports the hypothesis that the change in burial practice was the result of the influx of foreign people, who were being allowed to keep their own burial customs, whereas some of the local inhabitants adapted the burial rites of foreign cultures, leading to a heterogeneous burial rite for some centuries