Antiparallel protocadherin homodimers use distinct affinity- and specificity-mediating regions in cadherin repeats 1-4

Protocadherins (Pcdhs) are cell adhesion and signaling proteins used by neurons to develop and maintain neuronal networks, relying on trans homophilic interactions between their extracellular cadherin (EC) repeat domains. We present the structure of the antiparallel EC1-4 homodimer of human PcdhγB3, a member of the γ subfamily of clustered Pcdhs. Structure and sequence comparisons of α, β, and γ clustered Pcdh isoforms illustrate that subfamilies encode specificity in distinct ways through diversification of loop region structure and composition in EC2 and EC3, which contains isoform-specific conservation of primarily polar residues. In contrast, the EC1/EC4 interface comprises hydrophobic interactions that provide non-selective dimerization affinity. Using sequence coevolution analysis, we found evidence for a similar antiparallel EC1-4 interaction in non-clustered Pcdh families. We thus deduce that the EC1-4 antiparallel homodimer is a general interaction strategy that evolved before the divergence of these distinct protocadherin families. DOI: http://dx.doi.org/10.7554/eLife.18449.00

Sequence co-evolution gives 3D contacts and structures of protein complexes

Protein–protein interactions are fundamental to many biological processes. Experimental screens have identified tens of thousands of interactions, and structural biology has provided detailed functional insight for select 3D protein complexes. An alternative rich source of information about protein interactions is the evolutionary sequence record. Building on earlier work, we show that analysis of correlated evolutionary sequence changes across proteins identifies residues that are close in space with sufficient accuracy to determine the three-dimensional structure of the protein complexes. We evaluate prediction performance in blinded tests on 76 complexes of known 3D structure, predict protein–protein contacts in 32 complexes of unknown structure, and demonstrate how evolutionary couplings can be used to distinguish between interacting and non-interacting protein pairs in a large complex. With the current growth of sequences, we expect that the method can be generalized to genome-wide elucidation of protein–protein interaction networks and used for interaction predictions at residue resolution. DOI: http://dx.doi.org/10.7554/eLife.03430.00

The role of bounded rationality and imperfect information in subgame perfect implementation - an empirical investigation

In this paper we conduct a laboratory experiment to test the extent to which Moore and Repullo’s subgame perfect implementation mechanism induces truth-telling, both in a setting with perfect information and in a setting where buyers and sellers face a small amount of uncertainty regarding the good’s value. We find that Moore–Repullo mechanisms fail to implement truth-telling in a substantial number of cases even under perfect information about the valuation of the good. Our data further suggests that a substantial proportion of these lies are made by subjects who hold pessimistic beliefs about the rationality of their trading partners. Although the mechanism should—in theory—provide incentives for truth-telling, many buyers in fact believe that they can increase their expected monetary payoff by lying. The deviations from truth-telling become significantly more frequent and more persistent when agents face small amounts of uncertainty regarding the good’s value. Our results thus suggest that both beliefs about irrational play and small amounts of uncertainty about valuations may constitute important reasons for the absence of Moore–Repullo mechanisms in practice

Querying Formal Contexts with Answer Set Programs.

Recent studies showed how a seamless integration of formal concept analysis (FCA), logic of domains, and answer set programming (ASP) can be achieved. Based on these results for combining hierarchical knowledge with classical rule-based formalisms, we introduce an expressive common-sense query language for formal contexts. Although this approach is conceptually based on order-theoretic paradigms, we show how it can be implemented on top of standard ASP systems. Advanced features, such as default negation and disjunctive rules, thus become practically available for processing contextual data. © Springer-Verlag Berlin Heidelberg 2006

From the Desktop to the Grid: conversion of KNIME Workflows to gUSE

The Konstanz Information Miner is a user-friendly graphical workflow designer with a broad user base in industry and academia. Its broad range of embedded tools and its powerful data mining and visualization tools render it ideal for scientific workflows. It is thus used more and more in a broad range of applications. However, the free version typically runs on a desktop computer, restricting users if they want to tap into computing power. The grid and cloud User Support Environment is a free and open source project created for parallelized and distributed systems, but the creation of workflows with the included components has a steeper learning curve. In this work we suggest an easy to implement solution combining the ease-of-use of the Konstanz Information Miner with the computational power of distributed computing infrastructures. We present a solution permitting the conversion of workflows between the two platforms. This enables a convenient development, debugging, and maintenance of scientific workflows on the desktop. These workflows can then be deployed on a cloud or grid, thus permitting large-scale computation. To achieve our goals, we relied on a Common Tool Description XML file format which describes the execution of arbitrary programs in a structured and easily readable and parseable way. In order to integrate external programs into we employed the Generic KNIME Nodes extension