224 research outputs found

    Caractérisation de la réponse inflammatoire suite à une lésion de la moelle épinière

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    La respiration humaine au cycle 3 : problèmes construits et registres explicatifs mobilisés par les élèves dans le débat scientifique

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    Cet article propose des outils d’analyse de séquences d’enseignement sur la respiration dans deux classes, qui font une large place au débat scientifique. L’analyse des productions écrites en référence à une grille historique permet d’avancer quelques hypothèses sur les registres explicatifs mobilisés par les élèves. L’analyse des transcriptions des débats effectués conduit à la construction de plusieurs espaces de contraintes dans chaque classe, ce qui peut expliquer les difficultés rencontrées par les enseignantes pour amener les élèves vers une problématique commune proche des savoirs visés

    Neuropathic Pain Phenotype Does Not Involve the NLRP3 Inflammasome and Its End Product Interleukin-1β in the Mice Spared Nerve Injury Model.

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    The NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome is one of the main sources of interleukin-1β (IL-1β) and is involved in several inflammatory-related pathologies. To date, its relationship with pain has not been studied in depth. The aim of our study was to elucidate the role of NLRP3 inflammasome and IL-1β production on neuropathic pain. Results showed that basal pain sensitivity is unaltered in NLRP3-/- mice as well as responses to formalin test. Spared nerve injury (SNI) surgery induced the development of mechanical allodynia and thermal hyperalgesia in a similar way in both genotypes and did not modify mRNA levels of the NLRP3 inflammasome components in the spinal cord. Intrathecal lipopolysaccharide (LPS) injection increases apoptosis-associated speck like protein (ASC), caspase-1 and IL-1β expression in both wildtype and NLRP3-/- mice. Those data suggest that NLRP3 is not involved in neuropathic pain and also that other sources of IL-1β are implicated in neuroinflammatory responses induced by LPS

    Dynamic changes of DNA methylation and lung disease in cystic fibrosis: Lessons from a monogenic disease

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    Para avaliar se os níveis de metilação do DNA são responsáveis ​​pelas variações fenotípicas não hereditárias observadas entre pacientes com fibrose cística (FC). PACIENTES E MÉTODOS Usando o BeadChip de 450 K, nós perfilamos a metilação do DNA em células epiteliais nasais coletadas de 32 pacientes com FC e 16 controles. RESULTADOS Detectamos diferenças substanciais na metilação do DNA de até 55% (mudança β mediana de 0,13; IQR: 0,15-0,11) entre pacientes com FC e controles. Os níveis de metilação do DNA diferiram entre pacientes com FC leve e grave e se correlacionaram com a função pulmonar em 50 locais CpG. CONCLUSÃO Em amostras de FC, mudanças dinâmicas na metilação do DNA ocorreram em genes responsáveis ​​pela integridade do epitélio e pelas respostas inflamatórias e imunes, foram proeminentes em regiões genômicas transcricionalmente ativas e foram super-representadas em intensificadores ativos em tecidos pulmonares. ( Clinicaltrials.gov NCT02884622).To assess whether DNA methylation levels account for the noninherited phenotypic variations observed among cystic fibrosis (CF) patients. PATIENTS & METHODS Using the 450 K BeadChip, we profiled DNA methylation in nasal epithelial cells collected from 32 CF patients and 16 controls. RESULTS We detected substantial DNA methylation differences up to 55% (median β change 0.13; IQR: 0.15-0.11) between CF patients and controls. DNA methylation levels differed between mild and severe CF patients and correlated with lung function at 50 CpG sites. CONCLUSION In CF samples, dynamic changes of DNA methylation occurred in genes responsible for the integrity of the epithelium and the inflammatory and immune responses, were prominent in transcriptionally active genomic regions and were over-represented in enhancers active in lung tissues. ( Clinicaltrials.gov NCT02884622)

    Issues and special features of animal health research

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    In the rapidly changing context of research on animal health, INRA launched a collective discussion on the challenges facing the field, its distinguishing features, and synergies with biomedical research. As has been declared forcibly by the heads of WHO, FAO and OIE, the challenges facing animal health, beyond diseases transmissible to humans, are critically important and involve food security, agriculture economics, and the ensemble of economic activities associated with agriculture. There are in addition issues related to public health (zoonoses, xenobiotics, antimicrobial resistance), the environment, and animal welfare

    Risk assessment of spreading BSVs through the cultivation of interspecific hybrids harbouring infectious eBSVs

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    Infectious alleles of endogenous Banana streak viruses (eBSVs) are present in the genome of Musa balbisiana spp. Their activation by biotic and abiotic stresses lead to spontaneous infections by several species of Banana streak virus (BSV) in triploid (AAB) and tetraploid (AAAB) interspecific hybrids, making them the main constraint for breeding new banana interspecific hybrids and for exchanging germplasm. However the risk of spreading BSVs associated to the cultivation of interspecific hybrids has never been assessed, although such hybrids are grown over important areas throughout the Caribbean, Latin America and Africa. In order to tackle this issue, a study of the kinetics of activation of infectious alleles OL 1 and GF7, whose expression lead to spontaneous infections by BSOLV and BSGFV, respectively, was carried out in natural plantains French Clair, Pelipita and Macho x Hembra and hybrids FHIA-18 and FHIA-21 under field conditions in the Dominican Republic, Cuba and Guadeloupe. Experimental plots using similar randomized block designs and planting material originating from suckers, vitroplants or stem fragments were set up. Plants were monitored visually for symptoms and checked every 3 months by multiplex immunocapture PCR indexing for the presence of BSOLV and BSGFV. Results collected over 24 months showed that infectious alleles OL 1 and GF7 display differential expression levels, pointing to the existence of additional (plant) factors involved in their activation. They also showed that the mode of multiplication of the planting material influences expression levels. Preliminary results also suggested that infection by BSOLV and BSGFV does not have a major effect on fruit production, although additional data are needed to reach definite conclusions in this regard. Overall, this work contributes significantly to the development and implementation of appropriate strategies for evaluating and recommendations for mitigating the risks of spreading BSVs associated with the cultivation of banana interspecific hybrids. (Résumé d'auteur

    DNA Damage Repair Kinase DNA-Pk and cGAS Synergize To Induce Cancer-Related Inflammation in Glioblastoma

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    Cytosolic DNA promotes inflammatory responses upon detection by the cyclic GMP-AMP (cGAMP) synthase (cGAS). It has been suggested that cGAS downregulation is an immune escape strategy harnessed by tumor cells. Here, we used glioblastoma cells that show undetectable cGAS levels to address if alternative DNA detection pathways can promote pro-inflammatory signaling. We show that the DNA-PK DNA repair complex (i) drives cGAS-independent IRF3-mediated type I Interferon responses and (ii) that its catalytic activity is required for cGAS-dependent cGAMP production and optimal downstream signaling. We further show that the cooperation between DNA-PK and cGAS favors the expression of chemokines that promote macrophage recruitment in the tumor microenvironment in a glioblastoma model, a process that impairs early tumorigenesis but correlates with poor outcome in glioblastoma patients. Thus, our study supports that cGAS-dependent signaling is acquired during tumorigenesis and that cGAS and DNA-PK activities should be analyzed concertedly to predict the impact of strategies aiming to boost tumor immunogenicity

    Le gisement paléolithique multistratifié « les Bossats » à Ormesson (Seine-et-Marne, France) : palethnographie ou pâle ethnographie ? Une synthèse des huit premières années de fouille (2009-2016)

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    editorial reviewedÀ l'évidence, ces vingt dernières années ont vu en France, notamment, se développer en parallèle deux nouvelles façons de traiter le Paléolithique supérieur ancien qui ne sont pas antagonistes d'ailleurs. L'une consiste en une reprise des stratigraphies anciennes dans le Centre et le Sud-Ouest de la France plus spécifiquement et est associée à une meilleure redéfinition des entités culturelles par l'analyse détaillée des différentes composantes des systèmes techniques. L'autre s'efforce d'appliquer à cette période la démarche palethnographique, inféodée historiquement au Magdalénien du Bassin parisien. Il est vrai que peu de gisements autorisaient ce type d'approche, en raison d'une surface fouillée insuffisante ou d'un état de conservation médiocre, mais même lorsque les découvertes s'y prêtaient, le manque de temps et d'investissement freinait également toute velléité d'une étude approfondie des sites en question, qui aurait alors débouché sur une lecture palethnographique des lieux et des artefacts. À l'issue d'un PCR mené entre 1999 et 2005, nous pouvions ainsi légitimement nous demander si nous étions capables de jouer les ethnologues du passé pour le Paléolithique supérieur ancien dans le Bassin parisien. Les sites identifiés dans le cadre de ce programme de recherche étaient certes nombreux mais représentés surtout par des découvertes de surface, ils ne garantissaient pas un niveau d'analyse digne de ce qui a pu se faire depuis plus de 50 ans à Pincevent ou à Étiolles par exemple (Bodu et al., 2013). Il aura fallu attendre la découverte fortuite du gisement de plein-air d'Ormesson « les Bossats » (Seine-et-Marne, près de Nemours) au début des années 2000 pour que cette question trouve une réponse positive. Concernant, au départ, presqu'exclusivement des vestiges lithiques et osseux attribués au Gravettien, les premières fouilles menées en 2009 permirent d'identifier rapidement un second niveau d'occupation, d'attribution moustérienne. Les campagnes suivantes amenèrent à la découverte de cinq autres niveaux d'occupation paléolithiques, inégaux tant pour la surface couverte que pour l'état de conservation : un second niveau moustérien résultant vraisemblablement de palimpsestes, un ensemble châtelperronien, un autre solutréen, un quatrième badegoulien et enfin entre Châtelperronien et Gravettien, un foyer isolé sans vestiges archéologiques associés. Cette stratigraphie paléolithique de plein-air dilatée est le témoignage d'une forte occupation du lieu pendant près de 30 000 ans, ce qui s'explique notamment par la configuration particulière de la vallée à cet endroit. À la diversité chronologique des occupations préhistoriques répond une diversité des comportements économiques et techniques au sein des différentes sphères d'activités mais également des habitudes spatiales différentes. À l'issue des huit premières années de fouille (2009-2016), le site d'Ormesson « les Bossats » permet ainsi de développer une approche détaillée des comportements techniques, économiques, spatiaux de groupes culturels distincts ayant vécu durant 30 000 ans dans un cadre géomorphologique et plus globalement naturel, relativement identique. Dépassant le jeu de mot facile « palethnographie ou pâle ethnographie ? » à Ormesson « les Bossats », nous proposons ici quelques éléments de réponse

    A contact binary satellite of the asteroid (152830) Dinkinesh

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    Asteroids with diameters less than about 5 km have complex histories because they are small enough for radiative torques (that is, YORP, short for the Yarkovsky-O'Keefe-Radzievskii-Paddack effect)1 to be a notable factor in their evolution. (152830) Dinkinesh is a small asteroid orbiting the Sun near the inner edge of the main asteroid belt with a heliocentric semimajor axis of 2.19 au; its S-type spectrum3,4 is typical of bodies in this part of the main belt5. Here we report observations by the Lucy spacecraft as it passed within 431 km of Dinkinesh. Lucy revealed Dinkinesh, which has an effective diameter of only 720 m, to be unexpectedly complex. Of particular note is the presence of a prominent longitudinal trough overlain by a substantial equatorial ridge and the discovery of the first confirmed contact binary satellite, now named (152830) Dinkinesh I Selam. Selam consists of two near-equal-sized lobes with diameters of 210 m and 230 m. It orbits Dinkinesh at a distance of 3.1 km with an orbital period of about 52.7 h and is tidally locked. The dynamical state, angular momentum and geomorphologic observations of the system lead us to infer that the ridge and trough of Dinkinesh are probably the result of mass failure resulting from spin-up by YORP followed by the partial reaccretion of the shed material. Selam probably accreted from material shed by this event
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