Molecular and Structural Parallels between Gluten Pathogenic Peptides and Bacterial-Derived Proteins by Bioinformatics Analysis

Gluten-related disorders (GRDs) are a group of diseases that involve the activation of the immune system triggered by the ingestion of gluten, with a worldwide prevalence of 5%. Among them, Celiac disease (CeD) is a T-cell-mediated autoimmune disease causing a plethora of symptoms from diarrhea and malabsorption to lymphoma. Even though GRDs have been intensively studied, the environmental triggers promoting the diverse reactions to gluten proteins in susceptible individ-uals remain elusive. It has been proposed that pathogens could act as disease-causing environmental triggers of CeD by molecular mimicry mechanisms. Additionally, it could also be possible that unrecognized molecular, structural, and physical parallels between gluten and pathogens have a relevant role. Herein, we report sequence, structural and physical similarities of the two most relevant gluten peptides, the 33-mer and p31-43 gliadin peptides, with bacterial pathogens using bioinformatics going beyond the molecular mimicry hypothesis. First, a stringent BLASTp search using the two gliadin peptides identified high sequence similarity regions within pathogen-derived proteins, e.g., extracellular proteins from Streptococcus pneumoniae and Granulicatella sp. Second, molecular dynamics calculations of an updated α-2-gliadin model revealed close spatial localization and solvent-exposure of the 33-mer and p31-43 peptide, which was compared with the pathogen-related proteins by homology models and localization predictors. We found putative functions of the identified pathogen-derived sequence by identifying T-cell epitopes and SH3/WW-binding domains. Finally, shape and size parallels between the pathogens and the superstructures of gliadin peptides gave rise to novel hypotheses about activation of innate immunity and dysbiosis. Based on our structural findings and the similarities with the bacterial pathogens, evidence emerges that these pathologically relevant gluten-derived peptides could behave as non-replicating pathogens opening new research questions in the interface of innate immunity, microbiome, and food research.Fil: Vazquez, Diego Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Schilbert, Hanna M.. Universitat Bielefeld; AlemaniaFil: Dodero, Veronica Isabel. Universitat Bielefeld; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

eCultura. Platform for Preservation and Exploitation of Cultural Content

Poster presentado en Cultural Heritage on line (2009).The eCultura project aims at developing a semantically-enriched web platform that enables cultural heritage institutions to manage and exhibit the semantics of publicly available web assets at a minimal cost and with a short investments on required software infrastructure. The platform will provide a complete set of applications and services to enhance the user experience when accessing web-based contents of the cultural domain. These services include semantic wikis, multimedia annotations, timeline presentations, interactive maps, and so on, which are deployed on a common platform. The eCultura platform is integrated by a number of open source applications grounded on a semantic web infrastructure that supports the semantic integration of all services. Semantic web technologies enable to share information among these services, as well as provide interoperability with external systems. W3C knowledge representation languages and standards are used to describe concepts of the cultural domain and provide a semantically interoperable environment. Web 2.0 techniques are used to build user communities around the shared information of cultural institutions, having the specific goal of exploiting their knowledge base in learning and educational environments. The communication among software components and applications is based on a producer/consumer model. Some services, such as wikis and blogs, work as source of information and knowledge, while other services, such as interactive maps and timeline, work as consumers to exploit the semantically enriched information. The knowledge base is stored on a shared OWL repository gathering the semantics of diverse cultural fields, including the CIDOC reference model, the FRBR ontology and the MusicOntology

Applying Recommendations to Align Competences, Methodology, and Assessment in Telematics, Computing, and Electronic Engineering Courses

The alignment between competences, teachinglearning methodologies, and assessment is a key element of European higher education. This paper presents the efforts carried out by six telematics, computer science and electronic engineering education teachers toward achieving this alignment in their subjects. In a joint work with pedagogues, a set of recommended actions are identified. A selection of these actions are applied and evaluated in the six subjects. The cross analysis of the results indicates that the actions allow students to better understand the methodologies and assessments planned for the subjects, facilitate (self-) regulation, and increase students’ involvement in the subjects

Combination of DROOL rules and Protégé knowledge bases in the ONTO-H annotation tool

ONTO-H is a semi-automatic collaborative tool for the semantic annotation of documents, built as a Protégé 3.0 tab plug-in. Among its multiple functionalities aimed at easing the document annotation process, ONTO-H uses a rule-based system to create cascading annotations out from a single drag and drop operation from a part of a document into an already existing concept or instance of the domain ontology being used for annotation. It also gives support to the detection of name conflicts and instance duplications in the creation of the annotations. The rule system runs on top of the open source rule engine DROOLS and is connected to the domain ontology used for annotation by means of an ad-hoc programmed Java proxy

Dynamic Pressure Measurements During Vitrectomy in a Model of the Eye

Purpose: To accurately evaluate pressure changes during vitrectomy in a rigid model of the vitreous chamber and to test the efficiency of the EVA phacovitrectomy system (Dutch Ophthalmic Research Center) in terms of compensation of intraocular pressure variations. Methods: We tested 23-, 25-, and 27-gauge double-blade vitreous cutters in both vented global pressure control and automatic infusion compensation (AIC) modes in a vitreous chamber model, mimicking the real surgical procedure. Balanced salt solution and artificial vitreous, similar to the real vitreous body, were used. We tested both standard-flow (SF) and high-flow (HF) infusion systems, varying the infusion pressure between 20 and 40 mm Hg. In each experiment, flow rate was also measured. Results: Pressure drop was rapidly and efficiently compensated when 23-and 25-gauge cutters were used in AIC mode, with infusion pressures ranging between 30 and 55 mm Hg. The 27-gauge cutter was less efficient in compensating pressure variations. Pressure fluctuations related to the high-frequency motion of the cutter blade were small compared to the overall pressure variations. The use of the HF infusion system resulted in larger flow rates and lower pressure changes compared to the SF infusion system. Conclusions: Despite the rigid material of the model, the present pressure measurements are in line with previous studies performed on porcine eye. The use of AIC mode compensates intraoperative pressure drops efficiently, with both 23-and 25-gauge cutters. The HF infusion system is more efficient than the SF infusion system. Translational Relevance: The AIC infusion mode efficiently compensates intraopera-tive pressure drops, in both 23-and 25-gauge experimental vitrectomy. The HF infusion system resulted in larger flow rate and lower pressure changes

Stimuli-responsive selection of target DNA sequences by synthetic bZIP peptides

One of the strategies used by nature to regulate gene expression relies on the stimuli controlled combination of DNA-binding proteins. This in turn determines the target-binding site within the genome, and thereby whether a particular gene is activated or repressed. Here we demonstrate how a designed basic region leucine zipper-based peptide can be directed towards two different DNA sequences depending on its dimerization arrangement. While themonomeric peptide is non-functional, a C-terminal metallo-dimer recognizes the natural ATF/CREB-binding site (5'-ATGA cg TCAT-3'), and a N-terminal disulphide dimer binds preferentially to the swapped sequence (5-TCATcg ATGA-30'). As the dimerization mode can be efficiently controlled by appropriate external reagents, it is possible to reversibly drive the peptide to either DNA site in response to such specific inputs. This represents the firstexample of a designed molecule that can bind to more than one specific DNA sequence depending on changes in its environment.Fil: Mosquera, Jesus. Universidad de Santiago de Compostela. Facultad de Quimica. Departamento de Quimica Organica; EspañaFil: Jimenez Balsa, Adrian. Universidad de Santiago de Compostela. Facultad de Quimica. Departamento de Quimica Organica; EspañaFil: Dodero, Veronica Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Instituto de Química del Sur; Argentina. Universidad de Santiago de Compostela; EspañaFil: Vázquez, M. Eugenio . Universidad de Santiago de Compostela. Facultad de Quimica. Departamento de Quimica Organica; EspañaFil: Mascareñas, José L. . Universidad de Santiago de Compostela. Facultad de Quimica. Departamento de Quimica Organica; Españ

Do software models based on the UML aid in source-code comprehensibility? Aggregating evidence from 12 controlled experiments

In this paper, we present the results of long-term research conducted in order to study the contribution made by software models based on the Unified Modeling Language (UML) to the comprehensibility of Java source-code deprived of comments. We have conducted 12 controlled experiments in different experimental contexts and on different sites with participants with different levels of expertise (i.e., Bachelor’s, Master’s, and PhD students and software practitioners from Italy and Spain). A total of 333 observations were obtained from these experiments. The UML models in our experiments were those produced in the analysis and design phases. The models produced in the analysis phase were created with the objective of abstracting the environment in which the software will work (i.e., the problem domain), while those produced in the design phase were created with the goal of abstracting implementation aspects of the software (i.e., the solution/application domain). Source-code comprehensibility was assessed with regard to correctness of understanding, time taken to accomplish the comprehension tasks, and efficiency as regards accomplishing those tasks. In order to study the global effect of UML models on source-code comprehensibility, we aggregated results from the individual experiments using a meta-analysis. We made every effort to account for the heterogeneity of our experiments when aggregating the results obtained from them. The overall results suggest that the use of UML models affects the comprehensibility of source-code, when it is deprived of comments. Indeed, models produced in the analysis phase might reduce source-code comprehensibility, while increasing the time taken to complete comprehension tasks. That is, browsing source code and this kind of models together negatively impacts on the time taken to complete comprehension tasks without having a positive effect on the comprehensibility of source code. One plausible justification for this is that the UML models produced in the analysis phase focus on the problem domain. That is, models produced in the analysis phase say nothing about source code and there should be no expectation that they would, in any way, be beneficial to comprehensibility. On the other hand, UML models produced in the design phase improve source-code comprehensibility. One possible justification for this result is that models produced in the design phase are more focused on implementation details. Therefore, although the participants had more material to read and browse, this additional effort was paid back in the form of an improved comprehension of source code

Insights into gliadin supramolecular organization at digestive pH 3.0

Herrera MG, Vazquez DS, Sreij R, et al. Insights into gliadin supramolecular organization at digestive pH 3.0. COLLOIDS AND SURFACES B-BIOINTERFACES. 2018;165:363-370.Alpha-gliadin is a highly immunogenic protein from wheat, which is associated with many human diseases, like celiac disease and non-celiac gluten sensitivity. Because of that, gliadin solution is subject to intense biomedical research. However, the physicochemical nature of the employed gliadin solution at physiological pH is not understood. Herein, we present a supramolecular evaluation of the alpha-gliadin protein in water at pH 3.0 by dynamic light scattering (DLS), cryo-transmission electron microscopy (cryoTEM) and small-angle-.X-ray scattering (SAXS). We report that at 0.5 wt% concentration (0.1 mg/ml), gliadin is already a colloidal polydisperse system with an average hydrodynamic radius of 30 +/- 10 nm. By cryo-TEM, we detected mainly large clusters. However, it was possible to visualise for the first time prolate oligomers of around 68 nm and 103 nm, minor and major axis, respectively. SAXS experiments support the existence of prolate/rod-like structures. At 1.5 wt% concentration gliadin dimers, small oligomers and large clusters coexist. The radius of gyration (R-g1) of gliadin dimer is 5.72 +/- 0.23 nm with a dimer cross-section (R-c) of 1.63 nm, and an average length of around 19 nm, this suggests that gliadin dimers are formed longitudinally. Finally, our alpha-gliadin 3D model, obtained by ab initio prediction and analysed by molecular dynamics (MD), predicts that two surfaces prone to aggregation are exposed to the solvent, at the C-terminus. We hypothesise that this region may be involved in the dimerisation process of alpha-gliadin. (C) 2018 Elsevier B.V. All rights reserved

From celiac disease to coccidia infection and vice-versa: the polyQ peptide CXCR3-interaction axis

Zonulin is a physiological modulator of intercellular tight junctions, which upregulation is involved in several diseases like celiac disease (CeD). The polyQ gliadin fragment binds to the CXCR3 chemokine receptor that activates zonulin upregulation, leading to increased intestinal permeability in humans. Here, we report a general hypothesis based on the structural connection between the polyQ sequence of the immunogenic CeD protein, gliadin, and enteric coccidian parasites proteins. Firstly, a novel interaction pathway between the parasites and the host is described based on the structural similarities between polyQ gliadin fragments and the parasite proteins. Secondly, a potential connection between coccidial infections as a novel environmental trigger of CeD is hypothesized. Therefore, this report represents a promising breakthrough for coccidian research and points out the potential role of coccidian parasites as a novel trigger of CeD that might define a preventive strategy for gluten-related disorders in general. Also see the video abstract here: https://youtu.be/oMaQasStcFI.Fil: Lauxmann, Martin Alexander. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Brandenburg Medical School; AlemaniaFil: Vazquez, Diego Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB | Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB | Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB; ArgentinaFil: Schilbert, Hanna M.. Universitat Bielefeld; AlemaniaFil: Neubauer, Pia R.. Universitat Bielefeld; AlemaniaFil: Lammers, Karen M.. Tubascan Ltd; Países BajosFil: Dodero, Veronica Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universitat Bielefeld; Alemani