Aphanomyces euteiches Cell Wall Fractions Containing Novel Glucan-Chitosaccharides Induce Defense Genes and Nuclear Calcium Oscillations in the Plant Host Medicago truncatula

[EN] N-acetylglucosamine-based saccharides (chitosaccharides) are components of microbial cell walls and act as molecular signals during host-microbe interactions. In the legume plant Medicago truncatula, the perception of lipochitooligosaccharide signals produced by symbiotic rhizobia and arbuscular mycorrhizal fungi involves the Nod Factor Perception (NFP) lysin motif receptor-like protein and leads to the activation of the so-called common symbiotic pathway. In rice and Arabidopsis, lysin motif receptors are involved in the perception of chitooligosaccharides released by pathogenic fungi, resulting in the activation of plant immunity. Here we report the structural characterization of atypical chitosaccharides from the oomycete pathogen Aphanomyces euteiches, and their biological activity on the host Medicago truncatula. Using a combination of biochemical and biophysical approaches, we show that these chitosaccharides are linked to β-1,6-glucans, and contain a β-(1,3;1,4)-glucan backbone whose β-1,3-linked glucose units are substituted on their C-6 carbon by either glucose or N-acetylglucosamine residues. This is the first description of this type of structural motif in eukaryotic cell walls. Glucan-chitosaccharide fractions of A. euteiches induced the expression of defense marker genes in Medicago truncatula seedlings independently from the presence of a functional Nod Factor Perception protein. Furthermore, one of the glucan-chitosaccharide fractions elicited calcium oscillations in the nucleus of root cells. In contrast to the asymmetric oscillatory calcium spiking induced by symbiotic lipochitooligosaccharides, this response depends neither on the Nod Factor Perception protein nor on the common symbiotic pathway. These findings open new perspectives in oomycete cell wall biology and elicitor recognition and signaling in legumes.SIThis work is part of the “Laboratoire d’Excellence” (LABEX) entitled TULIP (ANR -10-LABX-41); it was funded by the Région Midi-Pyrénées, the CNRS (PhD grant INEE 36 to AN), and the French Agence Nationale de la Recherche (ANR-08-BLAN-0208-01 “Sympasignal”)

A first-in-human study investigating biodistribution, safety and recommended dose of a new radiolabeled MAb targeting FZD10 in metastatic synovial sarcoma patients

Background: Synovial Sarcomas (SS) are rare tumors occurring predominantly in adolescent and young adults with a dismal prognosis in advanced phases. We report a first-in-human phase I of monoclonal antibody (OTSA-101) targeting FZD10, overexpressed in most SS but not present in normal tissues, labelled with radioisotopes and used as a molecular vehicle to specifically deliver radiation to FZD10 expressing SS lesions. Methods: Patients with progressive advanced SS were included. In the first step of this trial, OTSA-101 in vivo biodistribution and lesions uptake were evaluated by repeated whole body planar and SPECT-CT scintigraphies from H1 till H144 after IV injection of 187 MBq of 111In-OTSA-101. A 2D dosimetry study also evaluated the liver absorbed dose when using 90Y-OTSA-101. In the second step, those patients with significant tumor uptake were randomized between 370 MBq (Arm A) and 1110 MBq (Arm B) of 90Y-OTSA-101 for radionuclide therapy. Results: From January 2012 to June 2015, 20 pts. (median age 43 years [21–67]) with advanced SS were enrolled. Even though 111In-OTSA-101 liver uptake appeared to be intense, estimated absorbed liver dose was less than 20 Gy for each patient. Tracer intensity was greater than mediastinum in 10 patients consistent with sufficient tumor uptake to proceed to treatment with 90Y-OTSA-101: 8 were randomized (Arm A: 3 patients and Arm B: 5 patients) and 2 were not randomized due to worsening PS. The most common Grade ≥ 3 AEs were reversible hematological disorders, which were more frequent in Arm B. No objective response was observed. Best response was stable disease in 3/8 patients lasting up to 21 weeks for 1 patient. Conclusions: Radioimmunotherapy targeting FZD10 is feasible in SS patients as all patients presented at least one lesion with 111In-OTSA-101 uptake. Tumor uptake was heterogeneous but sufficient to select 50% of pts. for 90Y-OTSA-101 treatment. The recommended activity for further clinical investigations is 1110 MBq of 90Y-OTSA-101. However, because of hematological toxicity, less energetic particle emitter radioisopotes such as Lutetium 177 may be a better option to wider the therapeutic index. Trial registration: The study was registered on the NCT01469975 ( https://clinicaltrials.gov/ct2/show/NCT01469975 ) website with a registration code NCT01469975 on November the third, 2011

Is there a space–time continuum in olfaction?

The coding of olfactory stimuli across a wide range of organisms may rely on fundamentally similar mechanisms in which a complement of specific odorant receptors on olfactory sensory neurons respond differentially to airborne chemicals to initiate the process by which specific odors are perceived. The question that we address in this review is the role of specific neurons in mediating this sensory system—an identity code—relative to the role that temporally specific responses across many neurons play in producing an olfactory perception—a temporal code. While information coded in specific neurons may be converted into a temporal code, it is also possible that temporal codes exist in the absence of response specificity for any particular neuron or subset of neurons. We review the data supporting these ideas, and we discuss the research perspectives that could help to reveal the mechanisms by which odorants become perceptions

New Insights into the Evolution of Wolbachia Infections in Filarial Nematodes Inferred from a Large Range of Screened Species

Wolbachia are intriguing symbiotic endobacteria with a peculiar host range that includes arthropods and a single nematode family, the Onchocercidae encompassing agents of filariases. This raises the question of the origin of infection in filariae. Wolbachia infect the female germline and the hypodermis. Some evidences lead to the theory that Wolbachia act as mutualist and coevolved with filariae from one infection event: their removal sterilizes female filariae; all the specimens of a positive species are infected; Wolbachia are vertically inherited; a few species lost the symbiont. However, most data on Wolbachia and filaria relationships derive from studies on few species of Onchocercinae and Dirofilariinae, from mammals.We investigated the Wolbachia distribution testing 35 filarial species, including 28 species and 7 genera and/or subgenera newly screened, using PCR, immunohistochemical staining, whole mount fluorescent analysis, and cocladogenesis analysis. (i) Among the newly screened Onchocercinae from mammals eight species harbour Wolbachia but for some of them, bacteria are absent in the hypodermis, or in variable density. (ii) Wolbachia are not detected in the pathological model Monanema martini and in 8, upon 9, species of Cercopithifilaria. (iii) Supergroup F Wolbachia is identified in two newly screened Mansonella species and in Cercopithifilaria japonica. (iv) Type F Wolbachia infect the intestinal cells and somatic female genital tract. (v) Among Oswaldofilariinae, Waltonellinae and Splendidofilariinae, from saurian, anuran and bird respectively, Wolbachia are not detected.The absence of Wolbachia in 63% of onchocercids, notably in the ancestral Oswaldofilariinae estimated 140 mya old, the diverse tissues or specimens distribution, and a recent lateral transfer in supergroup F Wolbachia, modify the current view on the role and evolution of the endosymbiont and their hosts. Further genomic analyses on some of the newly sampled species are welcomed to decipher the open questions

Cybercriminalité et Droit : les Enjeux d’une Redéfinition

Since 2016, cybercrime generates more income for offenders than traditional crime. The development of the Internet, and of digital technology in general, has enabled many offences to be committed and thus has made its entry into the majority of branches of criminal law: offences against property, State security personality, etc. Yet, despite all the legislative developments, there is still one branch of criminal law where digital technology has not made its entry: offences against the physical integrity of the person. Doesn\u27t this rejection, however logical, raise questions? The exponential development of objects connected to the Internet allows us to envisage that these attacks will become a reality. Pacemakers, cars, aeroplanes, many are examples of tools that can be the target of hackers. The law has not remained inactive faced with these developments, but its answers are mainly defensive: thinking about the recognition of the notion of digital weapon is necessary. Depuis 2016, la cybercriminalité génère plus de revenus pour les délinquants que la criminalité traditionnelle. Le développement d\u27Internet, et du numérique en général, a permis de faciliter la commission de bon nombre d\u27infractions et a fait son entrée dans la majorité des branches du Droit pénal : atteintes aux biens, à la sûreté de l\u27État, à la personnalité, etc. Malgré les évolutions législatives, il reste une branche du Droit pénal où le numérique n\u27a pas fait son entrée : l\u27atteinte à l\u27intégrité physique de la personne. Ce rejet, pourtant logique, ne pose-t-il pas question ? Le développement exponentiel des objets connectés à Internet permet d\u27envisager que ces atteintes deviennent réalité. Pacemakers, voitures, avions, nombreux sont les exemples d\u27outils pouvant être la cible de hackers. Le droit n’est pas resté inactif face à ces évolutions mais ses réponses sont défensives : penser la reconnaissance de la notion d’arme numérique est nécessaire

Droits et obligations des sportifs sélectionnés

Règles à respecter par les athlètes sélectionnés pour les Jeux olympiques : tenues de la délégation olympique, utilisation du droit à l'image, couverture médiatique, communication par les blogs et réseaux sociaux..

Etudes de systèmes d'anticoïncidence pour les missions spatiales X et Gamma, Simbol-X, IXO et Astro-H

L'astronomie X permet de comprendre et d'explorer les phénomènes les plus énergétiques de notre univers. Les performances scientifiques des futures missions X nécessitent un détecteur avec un niveau très faible de fond, et sa réduction devient un enjeu majeur pour l'obtention de hautes performances des télescopes spatiaux. Cela implique des simulations approfondies et des systèmes de rejet efficaces. Il nécessite également une très bonne connaissance des détecteurs qui seront protégés. Durant ma thèse, j'ai acquis une forte expérience en participant à la conception, les tests et l'optimisation de la protection active et passive de la mission Simbol-X, un téléscope spatial franco-italien dédié à l'observation des rayons X, dans la gamme d'énergie 0,1 à 80 keV. Ce blindage est composé de scintillateurs plastiques et de fibres optiques collées sur celui-ci et d'une lecture par photomultiplicateur multi-anode. J'étais également responsable d'effectuer les essais de performance des détecteurs et de simulations avec les logiciels Monte-Carlo GEANT4 et SLitrani. Le projet Simbol-X a cessé en Mars 2009. Considérant que notre travail sur Simbol-X peut être étendu à d'autres missions X, nous avons suivi une R&D CNES sur l'étude des systèmes de rejet de fond en vue du télescope IXO/HXI, dont le système d'anticoïncidence est constitué d'un cristal de BGO lu par un photodiode. J'ai également participé à la conception et aux tests du modèle de laboratoire de ce système, refroidi grâce à un système Peltier. J'ai également contribué à l'étude d'un cristal de LaBr3, un nouveau type de détecteur scintillant, qui semble très prometteur pour les futurs systèmes de réduction de fond.X-ray astronomy allows us to understand and explore the most energetic phenomena in the Universe. The scientific performances of future hard X-ray missions necessitate a very low detector background reduction is thus a main issue for obtaining high performance space telescopes. This implies thorough background simulations, and efficient rejection systems. It necessitates also a very good knowledge of the detectors to be shielded. During my PHD, I got a strong experience on these issues by participating to the conception, tests and optimization of the active and passive shielding of the Simbol-X mission, a French-Italian space telescope dedicated to observe the X-ray sky, in the 0.1 to 80 keV energy band. This shielding is made of plastic scintillators with optical fibers glued on it and readout by multi-anode photomultiplier. I was also responsible of performing the detectors performance tests and the consequent simulations with the GEANT4 and SLitrani Monte-Carlo simulation software. The Simbol-X project has stopped in March 2009. Considering that our work on Simbol-X may be naturally extended to other X-ray missions, we have followed up with a CNES R&D project on the study of background rejection systems mainly in view the IXO/HXI telescope, whose anticoincidence is constituted by BGO blocks readout by APD diods. During my PHD, I have then also participated to the conception and test of the laboratory model of this anticoincidence, cooled down to -20C thanks to a Peltier system. I have also contributed to the study of LaBr3 detectors, a new kind of scintillating detector, which seems very promising for future background reduction systems.PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF