Vitronectin binds to a specific stretch within the head region of Yersinia adhesin A and thereby modulates Yersinia enterocolitica host interaction

Complement resistance is an important virulence trait of Yersinia enterocolitica (Ye) . The predominant virulence factor expressed by Ye is Yersinia adhesin A (YadA), which enables bacterial attachment to host cells and extracellular matrix and additionally allows the acquisition of soluble serum factors. The serum glycoprotein vitronectin (Vn) acts as an inhibitory regulator of the terminal complement complex by inhibiting the lytic pore formation. Here, we show YadA-mediated direct interaction of Ye with Vn and investigated the role of this Vn binding during mouse infection in vivo. Using different Yersinia strains, we identified a short stretch in the YadA head domain of Ye O:9 E40, similar to the ‘uptake region’ of Y. pseudotuberculosis YPIII YadA, as crucial for efficient Vn binding. Using recombinant fragments of Vn, we found the C-terminal part of Vn, including heparin-binding domain 3, to be responsible for binding to YadA. Moreover, we found that Vn bound to the bacterial surface is still functionally active and thus inhibits C5b-9 formation. In a mouse infection model, we demonstrate that Vn reduces complement-mediated killing of Ye O:9 E40 and, thus, improved bacterial survival. Taken together, these findings show that YadA-mediated Vn binding influences Ye pathogenesis

A SPARQL Query Transformation Rule Language — Application to Retrieval and Adaptation in Case-Based Reasoning

International audienceThis paper presents SQTRL, a language for transformation rules for SPARQL queries, a tool associated with it, and how it can be applied to retrieval and adaptation in case-based reasoning (CBR). Three applications of SQTRL are presented in the domains of cooking and digital humanities. For a CBR system using RDFS for representing cases and domain knowledge, and SPARQL for its query language, case retrieval with SQTRL consists in a minimal modification of the query so that it matches at least a source case. Adaptation based on the modification of an RDFS base can also be handled with the help of this tool. SQTRL and its tool can therefore be used for several goals related to CBR systems based on the semantic web standards RDFS and SPARQL

Incorporating temporal-bounded CBR techniques in real-time agents

Nowadays, MAS paradigm tries to move Computation to a new level of abstraction: Computation as interaction, where large complex systems are seen in terms of the services they offer, and consequently in terms of the entities or agents providing or consuming services. However, MAS technology is found to be lacking in some critical environments as real-time environments. An interaction-based vision of a real-time system involves the purchase of a responsibility by any entity or agent for the accomplishment of a required service under possibly hard or soft temporal conditions. This vision notably increases the complexity of these kinds of systems. The main problem in the architecture development of agents in real-time environments is with the deliberation process where it is difficult to integrate complex bounded deliberative processes for decision-making in a simple and efficient way. According to this, this work presents a temporal-bounded deliberative case-based behaviour as an anytime solution. More specifically, the work proposes a new temporal-bounded CBR algorithm which facilitates deliberative processes for agents in real-time environments, which need both real-time and deliberative capabilities. The paper presents too an application example for the automated management simulation of internal and external mail in a department plant. This example has allowed to evaluate the proposal investigating the performance of the system and the temporal-bounded deliberative case-based behaviour. 2010 Elsevier Ltd. All rights reserved.This work is supported by TIN2006-14630-C03-01 projects of the Spanish government, GVPRE/2008/070 project, FEDER funds and CONSOLIDER-INGENIO 2010 under Grant CSD2007-00022.Navarro Llácer, M.; Heras Barberá, SM.; Julian Inglada, VJ.; Botti Navarro, VJ. (2011). Incorporating temporal-bounded CBR techniques in real-time agents. Expert Systems with Applications. 38(3):2783-2796. https://doi.org/10.1016/j.eswa.2010.08.070S2783279638

Antibiotic-induced release of small extracellular vesicles (exosomes) with surface-associated DNA

Recently, biological roles of extracellular vesicles (which include among others exosomes, microvesicles and apoptotic bodies) have attracted substantial attention in various fields of biomedicine. Here we investigated the impact of sustained exposure of cells to the fluoroquinolone antibiotic ciprofloxacin on the released extracellular vesicles. Ciprofloxacin is widely used in humans against bacterial infections as well as in cell cultures against Mycoplasma contamination. However, ciprofloxacin is an inducer of oxidative stress and mitochondrial dysfunction of mammalian cells. Unexpectedly, here we found that ciprofloxacin induced the release of both DNA (mitochondrial and chromosomal sequences) and DNA-binding proteins on the exofacial surfaces of small extracellular vesicles referred to in this paper as exosomes. Furthermore, a label-free optical biosensor analysis revealed DNA-dependent binding of exosomes to fibronectin. DNA release on the surface of exosomes was not affected any further by cellular activation or apoptosis induction. Our results reveal for the first time that prolonged low-dose ciprofloxacin exposure leads to the release of DNA associated with the external surface of exosomes

Highlights of the São Paulo ISEV workshop on extracellular vesicles in cross-kingdom communication

In the past years, extracellular vesicles (EVs) have become an important field of research since EVs have been found to play a central role in biological processes. In pathogens, EVs are involved in several events during the host–pathogen interaction, including invasion, immunomodulation, and pathology as well as parasite–parasite communication. In this report, we summarised the role of EVs in infections caused by viruses, bacteria, fungi, protozoa, and helminths based on the talks and discussions carried out during the International Society for Extracellular Vesicles (ISEV) workshop held in São Paulo (November, 2016), Brazil, entitled Cross-organism Communication by Extracellular Vesicles: Hosts, Microbes and Parasites. © 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.11Ysciescopu

On the role of computers in creativity-support systems

We report here on our experiences with designing computer-based creativity-support systems over several years. In particular, we present the design of three different systems incorporating different mechanisms of creativity. One of them uses an idea proposed by Rodari to stimulate imagination of the children in writing a picture-based story. The second one is aimed to model creativity in legal reasoning, and the third one uses low-level perceptual similarities to stimulate creation of novel conceptual associations in unrelated pictures.We discuss lessons learnt from these approaches, and address their implications for the question of how far creativity can be tamed by algorithmic approaches

Acquisition of Complement Inhibitor Serine Protease Factor I and Its Cofactors C4b-Binding Protein and Factor H by Prevotella intermedia

Infection with the Gram-negative pathogen Prevotella intermedia gives rise to periodontitis and a growing number of studies implies an association of P. intermedia with rheumatoid arthritis. The serine protease Factor I (FI) is the central inhibitor of complement degrading complement components C3b and C4b in the presence of cofactors such as C4b-binding protein (C4BP) and Factor H (FH). Yet, the significance of complement inhibitor acquisition in P. intermedia infection and FI binding by Gram-negative pathogens has not been addressed. Here we show that P. intermedia isolates bound purified FI as well as FI directly from heat-inactivated human serum. FI bound to bacteria retained its serine protease activity as shown in degradation experiments with 125I-labeled C4b. Since FI requires cofactors for its activity we also investigated the binding of purified cofactors C4BP and FH and found acquisition of both proteins, which retained their activity in FI mediated degradation of C3b and C4b. We propose that FI binding by P. intermedia represents a new mechanism contributing to complement evasion by a Gram-negative bacterial pathogen associated with chronic diseases