Plant Insecticide L-Canavanine Repels Drosophila via the Insect Orphan GPCR DmX

An orphan G-protein-coupled gustatory receptor mediates detection of the plant poison L-canavanine in fruit flies

Highly potent HIV inhibition: engineering a key anti-HIV structure from PSC-RANTES into MIP-1β/CCL4

The HIV coreceptor CCR5 is a validated target for both the prevention and therapy of HIV infection. PSC-RANTES, an N-terminally modified analogue of one of the natural chemokine ligands of CCR5 (RANTES/CCL5), is a potent inhibitor of HIV entry into target cells. Here, we set out to engineer the anti-HIV activity of PSC-RANTES into another natural CCR5 ligand (MIP-1β/CCL4), by grafting into it the key N-terminal pharmacophore region from PSC-RANTES. We were able to identify MIP-1β/CCL4 analogues that retain the receptor binding profile of MIP-1β/CCL4, but acquire the very high anti-HIV potency and characteristic inhibitory mechanism of PSC-RANTES. Unexpectedly, we discovered that in addition to N-terminal structures from PSC-RANTES, the side chain of Lys33 is also necessary for full anti-HIV potenc

Sound production mechanism in Gobius paganellus (Gobiidae)

Gobiidae, the largest fish family (>1500 species), has species from at least 10 genera that produce sounds for communication. Studies focused on goby sound production mechanisms have suggested that sounds are produced by the forcible ejection of water through small apertures in the opercles (hydrodynamic mechanism). The present study was a multidisciplinary investigation (morphology, muscle histology, high-speed video, sound analysis and electromyography) of the sound emission mechanism in Gobius paganellus, which produces both pulsed and tonal calls. Two populations were used, from Brittany and Venice. In the French population, sounds were accompanied by a suite of coordinated movements of the buccal, branchial and opercular regions. This was not the case in the Venetian population, and thus the direct role of head movements in sound production was rejected. The hydrodynamic mechanism hypothesis was also rejected in G. paganellus on the basis of sound oscillogram shape and because sounds are still produced after the opercles and hyohyoid muscles are cut. The use of both electromyography and electron microscopy showed that the levator pectoralis muscle, which originates on the skull and inserts on the dorsal tip of the cleithrum, is involved in sound production. We propose that the contraction of this muscle and associated vibration of the large radials is used to make sounds. In addition, we propose that different sound types (pulsed sounds and tonal calls) could occur because of differences in fish size

Lymphopenia combined with low TCR diversity (divpenia) predicts poor overall survival in metastatic breast cancer patients

Lymphopenia (< 1Giga/L) detected before initiation of chemotherapy is a predictive factor for death in metastatic solid tumors. Combinatorial T cell repertoire (TCR) diversity was investigated and tested either alone or in combination with lymphopenia as a prognostic factor at diagnosis for overall survival (OS) in metastatic breast cancer (MBC) patients. The combinatorial TCR diversity was measured by semi quantitative multi-N-plex PCR on blood samples before the initiation of the first line chemotherapy in a development (n = 66) and validation (n = 67) MBC patient cohorts. A prognostic score, combining lymphocyte count and TCR diversity was evaluated. Univariate and multivariate analyses of prognostic factors for OS were performed in both cohorts. Lymphopenia and severe restriction of TCR diversity called “divpenia” (diversity ≤ 33%) were independently associated with shorter OS. Lympho-divpenia combining lymphopenia and severe divpenia accurately identified patients with poor OS in both cohorts (7.6 and 10.6 vs 24.5 and 22.9 mo). In multivariate analysis including other prognostic clinical factors, lympho-divpenia was found to be an independent prognostic factor in the pooled cohort (p = 0.005) along with lack of HER2 and hormonal receptors expression (p = 0.011) and anemia (p = 0.009). Lympho-divpenia is a novel prognostic factor that will be used to improve quality of MBC patients’ medical care

PIAF : développer la Pensée Informatique et Algorithmique dans l'enseignement Fondamental

Version étendue d'un article présenté au colloque Didapro8.Dans cet article, nous présentons les objectifs et premières réalisations du projet PIAF soutenu par l'Union Européenne et visant à développer l'apprentissage de la pensée informatique et algorithmique dans l'enseignement fondamental. Ce projet rassemble des chercheur·e·s en sciences de l'éducation et en informatique, provenant de quatre pays (Allemagne, Belgique, France et Luxembourg), autour du thème de la formation des enseignant·e·s. Plus concrètement, il s'agit de dénir un cadre (référentiel de compétences, scénarios pédagogiques) permettant aux enseignant·e·s de (i) s'approprier le concept de pensée informatique et algorithmique et de (ii) mettre en ÷uvre des activités d'apprentissage favorisant le développement de cette pensée chez l'enfant

PIAF : développer la Pensée Informatique et Algorithmique dans l'enseignement Fondamental

Version étendue d'un article présenté au colloque Didapro8.Dans cet article, nous présentons les objectifs et premières réalisations du projet PIAF soutenu par l'Union Européenne et visant à développer l'apprentissage de la pensée informatique et algorithmique dans l'enseignement fondamental. Ce projet rassemble des chercheur·e·s en sciences de l'éducation et en informatique, provenant de quatre pays (Allemagne, Belgique, France et Luxembourg), autour du thème de la formation des enseignant·e·s. Plus concrètement, il s'agit de dénir un cadre (référentiel de compétences, scénarios pédagogiques) permettant aux enseignant·e·s de (i) s'approprier le concept de pensée informatique et algorithmique et de (ii) mettre en ÷uvre des activités d'apprentissage favorisant le développement de cette pensée chez l'enfant

PIAF: Developing Computational and Algorithmic Thinking in Fundamental Education

Full text available at http://www.learntechlib.org/p/217317/International audienceIn this article, we present the objectives and first achievements of the PIAF project supported by the European Union and aiming at developing computational and algorithmic thinking in basic education. This project brings together researchers in educational sciences and computer science from four countries (Belgium, France, Germany and Luxembourg) around the theme of teacher training. More concretely, the aim is to define a framework (competency framework, pedagogical scenarios) enabling teachers to (i) appropriate the concept of computational and algorithmic thinking and (ii) implement learning activities that promote the development of this kind of thinking in children

PIAF : développer la Pensée Informatique et Algorithmique dans l'enseignement Fondamental

International audienceDans cet article, nous présentons les objectifs et premières réalisations du projet PIAF soutenu par l'Union Européenne et visant à développer l'apprentissage de la pensée informatique et algorithmique dans l'enseignement fondamental. Ce projet rassemble des chercheur·e·s en sciences de l'éducation et en informatique, provenant de quatre pays (Allemagne, Belgique, France et Luxembourg), autour du thème de la formation des enseignant·e·s. Plus concrètement, il s'agit de dénir un cadre (référentiel de compétences, scénarios pédagogiques) permettant aux enseignant·e·s de (i) s'approprier le concept de pensée informatique et algorithmique et de (ii) mettre en ÷uvre des activités d'apprentissage favorisant le développement de cette pensée chez l'enfant

PIAF : développer la Pensée Informatique et Algorithmique dans l'enseignement Fondamental

International audienceDans cet article, nous présentons les objectifs et premières réalisations du projet PIAF soutenu par l'Union Européenne et visant à développer l'apprentissage de la pensée informatique et algorithmique dans l'enseignement fondamental. Ce projet rassemble des chercheur·e·s en sciences de l'éducation et en informatique, provenant de quatre pays (Allemagne, Belgique, France et Luxembourg), autour du thème de la formation des enseignant·e·s. Plus concrètement, il s'agit de dénir un cadre (référentiel de compétences, scénarios pédagogiques) permettant aux enseignant·e·s de (i) s'approprier le concept de pensée informatique et algorithmique et de (ii) mettre en ÷uvre des activités d'apprentissage favorisant le développement de cette pensée chez l'enfant

The Chemerin/ChemR23 System Does Not Affect the Pro-Inflammatory Response of Mouse and Human Macrophages Ex Vivo

Macrophages constitute a major component of innate immunity and play an essential role in defense mechanisms against external aggressions and in inflammatory responses. Chemerin, a chemoattractant protein, is generated in inflammatory conditions, and recruits cells expressing the G protein-coupled receptor ChemR23, including macrophages. Chemerin was initially expected to behave as a pro-inflammatory agent. However, recent data described more complex activities that are either pro- or anti-inflammatory, according to the disease model investigated. In the present study, peritoneal macrophages were generated from WT or ChemR23−/− mice, stimulated with lipopolyssaccharide in combination or not with IFN-γ and the production of pro- (TNF-α, IL-1β and IL-6) and anti-inflammatory (IL-10) cytokines was evaluated using qRT-PCR and ELISA. Human macrophages generated from peripheral blood monocytes were also tested in parallel. Peritoneal macrophages from WT mice, recruited by thioglycolate or polyacrylamide beads, functionally expressed ChemR23, as assessed by flow cytometry, binding and chemotaxis assays. However, chemerin had no effect on the strong upregulation of cytokine release by these cells upon stimulation by LPS or LPS/IFN-γ, whatever the concentration tested. Similar data were obtained with human macrophages. In conclusion, our results rule out the direct anti-inflammatory effect of chemerin on macrophages ex vivo, described previously in the literature, despite the expression of a functional ChemR23 receptor in these cells