Crystal Structure of Two Anti-Porphyrin Antibodies with Peroxidase Activity

We report the crystal structures at 2.05 and 2.45 Å resolution of two antibodies, 13G10 and 14H7, directed against an iron(III)-αααβ-carboxyphenylporphyrin, which display some peroxidase activity. Although these two antibodies differ by only one amino acid in their variable λ-light chain and display 86% sequence identity in their variable heavy chain, their complementary determining regions (CDR) CDRH1 and CDRH3 adopt very different conformations. The presence of Met or Leu residues at positions preceding residue H101 in CDRH3 in 13G10 and 14H7, respectively, yields to shallow combining sites pockets with different shapes that are mainly hydrophobic. The hapten and other carboxyphenyl-derivatized iron(III)-porphyrins have been modeled in the active sites of both antibodies using protein ligand docking with the program GOLD. The hapten is maintained in the antibody pockets of 13G10 and 14H7 by a strong network of hydrogen bonds with two or three carboxylates of the carboxyphenyl substituents of the porphyrin, respectively, as well as numerous stacking and van der Waals interactions with the very hydrophobic CDRH3. However, no amino acid residue was found to chelate the iron. Modeling also allows us to rationalize the recognition of alternative porphyrinic cofactors by the 13G10 and 14H7 antibodies and the effect of imidazole binding on the peroxidase activity of the 13G10/porphyrin complexes

Cadherin-23, myosin VIIa and harmonin, encoded by Usher syndrome type I genes, form a ternary complex and interact with membrane phospholipids

Cadherin-23 is a component of early transient lateral links of the auditory sensory cells' hair bundle, the mechanoreceptive structure to sound. This protein also makes up the upper part of the tip links that control gating of the mechanoelectrical transduction channels. We addressed the issue of the molecular complex that anchors these links to the hair bundle F-actin core. By using surface plasmon resonance assays, we show that the cytoplasmic regions of the two cadherin-23 isoforms that do or do not contain the exon68-encoded peptide directly interact with harmonin, a submembrane PDZ (post-synaptic density, disc large, zonula occludens) domain-containing protein, with unusually high affinity. This interaction involves the harmonin Nter-PDZ1 supramodule, but not the C-terminal PDZ-binding motif of cadherin-23. We establish that cadherin-23 directly binds to the tail of myosin VIIa. Moreover, cadherin-23, harmonin and myosin VIIa can form a ternary complex, which suggests that myosin VIIa applies tension forces on hair bundle links. We also show that the cadherin-23 cytoplasmic region, harmonin and myosin VIIa interact with phospholipids on synthetic liposomes. Harmonin and the cytoplasmic region of cadherin-23, both independently and as a binary complex, can bind specifically to phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), which may account for the role of this phospholipid in the adaptation of mechanoelectrical transduction in the hair bundle. The distributions of cadherin-23, harmonin, myosin VIIa and PI(4,5)P2 in the growing and mature auditory hair bundles as well as the abnormal locations of harmonin and myosin VIIa in cadherin-23 null mutant mice strongly support the functional relevance of these interactions

Enhancing Cultural Awareness of EFL Learners Using a Flipped Classroom Model: The Perception of a Census

Teaching English as a Foreign Language is always of need for leading-edge methods and approaches, strategies and the teaching style of teachers.Putting into operation any of those mentioned is not as easy as anyone would have thought because we have to guarantee its effectiveness as well as the willingness of the students in order to implement it in the English department. A new instructional model needs to find its way to be applied at university-level, the flipped classroom model.This study is meant to explore students’ perceptions of using this strategy in teaching British and American civilizations course in the English Department at Barika University Center to ensure first-year learners’ understanding of the target culture, and awareness of cultural products, behaviors, and ideas.The study at hand is carried out through a descriptive method.The method of sampling in this study is the census since the whole population took part in this investigation. Forty (40) students were asked to answer a questionnaire that is related to both, the flipped strategy and cultural awareness.The results evinced a positive attitude towards using the flipped classroom in the culture and civilization module.Enseigner l'anglais en tant que langue étrangère a toujours besoin de s’appuyer sur les avancées de la didactique des langues étrangères. En effet, pour pouvoir aboutir à un enseignement efficace dans un contexte où l’anglais est langue étrangère, il faudra s’assurer de la participation active des étudiants. Ainsi, nous pensons que le modèle de la classe inversée devrait être mis en place au niveau universitaire. Cette étude vise à explorer les représentations qu’ont les étudiants du département d’anglais (Centre Universitaire de Barika) de la mise en place de ce modèle. Notre recherche se base sur l’hypothèse selon laquelle la mise en œuvre de ce modèle d’enseignement permettrait aux apprenants de première année de mieux appréhender la culture cible et de se conscientiser davantage des conceptions, des produits et des comportements culturels véhiculés par la langue anglaise. L’étude a été réalisée au moyen d’une méthode descriptive. Nous avons procédé par enquête à laquelle ont participé quarante (40) apprenants. Cette enquête par questionnaire dont les interrogations portent à la fois sur la stratégie inversée et sur la sensibilisation à la culture, a révélé, d’une manière générale, une attitude positive à l'égard du modèle de la classe inversée dans le module Culture et civilisation

Digital Video Conferencing in Algerian English Curricula to Enhance Learners’ Intercultural Communicative Competence: The Case of Doctoral Students at Batna-2 University/Algeria

This paper is an empirical research that attempts to make contributions to the English Language Pedagogy. It aims at introducing Digital Video Conferencing (DVC) in teaching Algerian students. The teaching/learning process has long been undergoing traditional teaching in the sense that classrooms tend to be teacher-centered. Teachers play the role of the ‘sage on the stage’, for they entirely depend on lecturing and monopolizing talk which drive learners to get bored, daydream, or even do something else such as texting friends (personal observation). Therefore, embedding DVC in the teaching/learning process is of paramount importance in order to swing the balance to a more learner-centered extreme; this would prioritize learners’ benefits and put their learning above all, and would restrict the role of the teacher to that of a ‘guide on the side’ since learners favour being involved in what they are exposed to. Albeit beneficial in getting learners engaged and in enhancing their Intercultural Communicative Competence (ICC), it is overlooked or granted to the elite of students. Nevertheless, many researchers opined and proved its usefulness in authenticating learning, in generating a sense of problem-solving urgency, in social engagement, in making learners blissfully productive, and in creating future teachers with a global profile.[i] In this investigation we adhere to the experimental research where a control group is taught through traditional teaching while an experimental one is part of the DVC programme at Batna-2 University. The results revealed the development of the components of ICC (Intercultural sensitivity, intercultural awareness, and intercultural adroitness) in the experimental group in comparison to the control group whose results did not impr

Caractérisation fonctionnelle et structurale de trois myosines non conventionnelles (la myosine VI, la myosine VIIa et la myosine IB d'Acanthamoeba)

Résumé français (1000 caractères maxi)Résumé anglais (idem)ORSAY-PARIS 11-BU Sciences (914712101) / SudocSudocFranceF

A High-level Formalism to Elaborate Context for a Context-aware Verification Approach

International audienceSpecification of precise requirement is a key element to realize effectively the model-checking verification. In a context-aware framework, the technique is considered through a set of specific environmental conditions in the form of contexts. A DSL, called CDL, has been proposed to facilitate the specification of requirement by context elaboration. However, it still low-level, error prone, difficult to grasp on complex models and its usability is mitigated. In this paper, we propose a high level formalism of CDL to assist the specification process by describing the system requirements using interaction overview diagrams. The objective is to generate CDL models through such intermediate formalism by orchestrating activity diagrams transformed from informal use cases. Thus, the semantic gap between informal and formal requirements is reduced and engineers are helped towards formal verification

An Automated Transformation Approach for Requirement Specification

International audienceUse cases are often useful in capturing requirements by defining goal-oriented set of interactions between the system and its environment. Formalization of precise requirement is then important for context-aware verification based on use cases scenarios in the form of contexts. In this paper, we propose a high-level formalism for expressing requirements based on interaction overview diagrams that orchestrate activity diagrams automatically transformed from textual use cases. Our approach is qualified as context-aware model-checking, it supposes the availability of a model of the system as concurrent communicating automata and a specification language for describing requirements. Specification of requirements is performed through transformation phases to generate intermediate artefacts able to reduce the semantic gap between informal and informal requirement. The transformation is based on meta-models implemented on Ecore environment, algorithm and rules are defined using QVT Relational language, and primarily illustrated on an academic example

Precise use cases in a context-aware model-checking approach

International audienceFormal verification exhibits well known benefits but comes at the price of formalising precise and sound requirements, what often remains a challenging task for engineers. We propose a high-level formalism for expressing requirements based on interaction overview diagrams, which orchestrate activity diagrams that we automatically derived from use cases. Informal requirements are transformed into scenarios which fuel a context-aware model-checking approach. The approach assumes the availability of a formal model of the system, such as concurrent and communicating automata and a set of requirements specified in the form of contexts, which point out boundaries between the system and its environment. The requirement specification approach blends elaboration and transformation phases. Thanks to this blending, the semantic gap between informal and formal requirements is reduced, while model-checking is improved by contexts modelling. As a consequence, engineers gain support for moving towards formal verification