ICT, new insights on old problems

In our research works, we used to look at the way in which artefacts become, for teachers as well as for students, instruments of their mathematical work. The questions of tools and technologies in mathematical education are now widely considered in our communities. The 100th anniversary of the creation of ICMI is the occasion to go back to history, to think on the possible contribution to mathematics learning of old (but not dead) artefacts to mathematics learning and to the instruments’s geneses.http://www.unige.ch/math/EnsMath/Rome2008/WG4/Papers/TROUMAS.pd

E-textbooks and connectivity: proposing an analytical framework

This paper is concerned with the development of e-textbooks. We claim that analysis (and design) of e-textbooks requires the development of a specific frame. Digital affordances provide particular opportunities (e.g. in terms of interactions between users) that require specific considerations for their analysis, as teachers and students use them for their individual and collective purposes. In this study, we develop a framework for mathematics e-textbook analysis, based on the notion of “connectivity.” We introduce criteria to assess the different aspects of connectivity and build an analysis grid for e-textbooks. We illustrate the framework proposed by analyzing 2 commonly used French grade 10 mathematics e-textbooks. The results of the analyses show that there are major differences between the 2 e-textbooks in terms of connectivity, which can be related to differences in their design. Beyond these 2 examples, we claim that focusing on connectivity is a useful and relevant way of analyzing e-textbooks, as it can provide a window into issues of interactivity, both practically and cognitively

Construction d'un modèle sémantique pour organiser les connaissances dédiées à l'agroécologie. Le cas d'Agro-PEPS/GECO

International audienceIn 2008, the RMT SdCi (Joint Technological Network on Innovative Cropping Systems) launched the develop-ment of a collaborative web tool, named Agro-PEPS, in response to the needs to redesign the mode of agricul-tural production. This tool aims to help practitioners to design, pilot, manage and learn innovative and efficient cropping systems. In 2015, the Ministry in charge of Agriculture decided to develop GECO within the framework of the ECOPHYTO plan. GECO is a collaborative knowledge management tool dedicated to agroecology. It is built up in using Agro-PEPS as a prototype. The necessarily systemic and complex nature of this type of knowledge leads us to develop a semantic model. This model allows the search engine to provide more accurate answers to queries and to sort them depending on their relevance. We present the first version of this model in this article. GECO will be online in a beta version in early 2017.Face aux besoins de reconception des modes de production agricoles, le Réseau Mixte Technologique SdCi (Systèmes de Culture Innovants) a lancé, dès 2008, le développement d'un outil web collaboratif, Agro-PEPS, pour aider les acteurs du terrain à concevoir, piloter, gérer et faire l'apprentissage de systèmes de culture innovants et performants. En 2015, le ministère en charge de l'agriculture a décidé, dans le cadre du plan Ecophyto, de développer GECO, dispositif de GEstion des COnnaissances, en utilisant Agro-PEPS comme prototype. GECO est un outil web collaboratif de gestion des connaissances dédiées à l'agroécologie. Le caractère nécessairement systémique et complexe de ce type de connaissances nous a conduits à développer un modèle sémantique. Ce modèle, dont une première version est présentée dans cet article, permet au moteur de recherche de fournir des réponses aux requêtes plus précises et dont la pertinence est hiérarchisée. GECO sera mis en ligne dans sa version béta début 2017

Integrating new memories into the hippocampal network activity space

By investigating the topology of neuronal co-activity, we found that mnemonic information spans multiple operational axes in the mouse hippocampus network. High-activity principal cells form the core of each memory along a first axis, segregating spatial contexts and novelty. Low-activity cells join co-activity motifs across behavioral events and enable their crosstalk along two other axes. This reveals an organizational principle for continuous integration and interaction of hippocampal memories

Exogenous LRRK2G2019S induces parkinsonian-like pathology in a nonhuman primate

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease among the elderly. To understand pathogenesis and to test therapies, animal models that faithfully reproduce key pathological PD hallmarks are needed. As a prelude to developing a model of PD, we tested the tropism, efficacy, biodistribution, and transcriptional impact of canine adenovirus type 2 (CAV-2) vectors in the brain of Microcebus murinus, a nonhuman primate that naturally develops neurodegenerative lesions. We show that introducing helper-dependent (HD) CAV-2 vectors results in long-term, neuron-specific expression at the injection site and in afferent nuclei. Although HD CAV-2 vector injection induced a modest transcriptional response, no significant adaptive immune response was generated. We then generated and tested HD CAV-2 vectors expressing LRRK2 (leucine-rich repeat kinase 2) and LRRK2 carrying a G2019S mutation (LRRK2G2019S), which is linked to sporadic and familial autosomal dominant forms of PD. We show that HD-LRRK2G2019S expression induced parkinsonian-like motor symptoms and histological features in less than 4 months

The histone demethylase JMJD2A/KDM4A links ribosomal RNA transcription to nutrients and growth factors availability

The interplay between methylation and demethylation of histone lysine residues is an essential component of gene expression regulation and there is considerable interest in elucidating the roles of proteins involved. Here we report that histone demethylase KDM4A/JMJD2A, which is involved in the regulation of cell proliferation and is overexpressed in some cancers, interacts with RNA Polymerase I, associates with active ribosomal RNA genes and is required for serum-induced activation of rDNA transcription. We propose that KDM4A controls the initial stages of transition from 'poised', non-transcribed rDNA chromatin into its active form. We show that PI3K, a major signalling transducer central for cell proliferation and survival, controls cellular localization of KDM4A and consequently its association with ribosomal DNA through the SGK1 downstream kinase. We propose that the interplay between PI3K/SGK1 signalling cascade and KDM4A constitutes a mechanism by which cells adapt ribosome biogenesis level to the availability of growth factors and nutrients

Towards chemical validation of Leishmania infantum ribose 5-phosphate isomerase as a drug target

Funding from the European Community's Seventh Framework Programme under grant agreements No. 602773 (Project KINDRED) was received for all partners in this work. This work also received funds from FCT - Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior through the Research Unit No. 4293 and project POCI-01-0145-FEDER-031013 (PTDC/SAUPAR/31013/2017 to NS); Individual funding from FCT through SFRH/BD/133485/2017 (to MS) and CEECIND/02362/2017 (to JT).Neglected tropical diseases caused by kinetoplastid parasites (Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp.) place a significant health and economic burden on developing nations worldwide. Current therapies are largely out-dated, inadequate and facing mounting drug resistance from the causative parasites. Thus, there is an urgent need for drug discovery and development. Target-led drug discovery approaches have focused on the identification of parasite enzymes catalysing essential biochemical processes, which significantly differ from equivalent proteins found in humans, thereby providing potentially exploitable therapeutic windows. One such target is ribose 5-phosphate isomerase B (RpiB), an enzyme involved in the non-oxidative branch of the pentose phosphate pathway, which catalyses the inter-conversion of D-ribose 5-phosphate and D-ribulose 5-phosphate. Although protozoan RpiB has been the focus of numerous targeted studies, compounds capable of selectively inhibiting this parasite enzyme have not been identified. Here, we present the results of a fragment library screening against Leishmania infantum RpiB, performed using thermal shift analysis. Hit fragments were shown to be effective inhibitors of LiRpiB in activity assays, and several were capable of selectively inhibiting parasite growth in vitro. These results support the identification of LiRpiB as a validated therapeutic target. The X-ray crystal structure of apo LiRpiB was also solved, permitting docking studies to assess how hit fragments might interact with LiRpiB to inhibit its activity. Overall, this work will guide structure-based development of LiRpiB inhibitors as anti-leishmanial agents.PostprintPeer reviewe