35 research outputs found

    Au-delĂ  de l’ethnicitĂ© et de la parentĂ© en Afghanistan : une approche ethnographique des liens transversaux de coopĂ©ration

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    La persistance du tribalisme et les tensions ethniques sont rĂ©guliĂšrement invoquĂ©es pour expliquer la prolongation de la guerre en Afghanistan. Le cas des Hazaras traitĂ© ici illustre la logique segmentaire inhĂ©rente Ă  l’anthropologie politique de l’Afghanistan. L’émergence progressive de la dimension ethnique sur la scĂšne politique afghane ainsi que le poids persistant des relations de parentĂ© ne doivent pas conduire Ă  nĂ©gliger la prĂ©gnance des liens transversaux de solidaritĂ© qui peuvent se dĂ©velopper entre voisins, camarades de classe ou collĂšgues. Les relations sociales quotidiennes suivent des logiques complexes. Pour faire face Ă  l’insĂ©curitĂ© et diminuer les risques, les Afghans tendent Ă  diversifier leurs relations sociales, mais aussi leurs activitĂ©s Ă©conomiques et leurs affiliations politiques. La fragmentation sociale et le factionnalisme politique apparaissent dĂšs lors comme des Ă©lĂ©ments structurels qui tendent Ă  un certain Ă©quilibre des entitĂ©s politiques en prĂ©sence.L’ethnicisation de la scĂšne politique afghane est situĂ©e dans son contexte historique ; elle apparaĂźt dĂšs lors comme le rĂ©sultat plus que la cause de la guerre.The persistence of tribalism and ethnic tensions are regularly invoked to explain the prolongation of the war in Afghanistan. The case of the Hazaras, treated here, illustrates the segmentary logic inherent in the political anthropology of Afghanistan. The gradual emergence of the ethnic dimension on the Afghan political scene and the lasting weight of kinship must not lead us to overlook the significance of transversal ties of solidarity, which can develop between neighbors, classmates or colleagues. Everyday social relations follow complex patterns. To cope with uncertainty and reduce risks, the Afghans tend to diversify their social relations as well as their economic activities and political affiliations. Social fragmentation and political factionalism therefore appear as structural elements that tend to keep a balance between political blocks. The ethnicization of the Afghan political scene is situated in its historical context; it appears thus to be the result more than the cause of the war

    Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system

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    Oligodendrocytes have been considered as a functionally homogeneous population in the central nervous system (CNS). We performed single-cell RNA sequencing on 5072 cells of the oligodendrocyte lineage from 10 regions of the mouse juvenile and adult CNS. Thirteen distinct populations were identified, 12 of which represent a continuum from Pdgfra(+) oligodendrocyte precursor cells (OPCs) to distinct mature oligodendrocytes. Initial stages of differentiation were similar across the juvenile CNS, whereas subsets of mature oligodendrocytes were enriched in specific regions in the adult brain. Newly formed oligodendrocytes were detected in the adult CNS and were responsive to complex motor learning. A second Pdgfra(+) population, distinct from OPCs, was found along vessels. Our study reveals the dynamics of oligodendrocyte differentiation and maturation, uncoupling them at a transcriptional level and highlighting oligodendrocyte heterogeneity in the CNS

    Disease-specific oligodendrocyte lineage cells arise in multiple sclerosis

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    Multiple sclerosis (MS) is characterized by an immune system attack targeting myelin, which is produced by oligodendrocytes (OLs). We performed single-cell transcriptomic analysis of OL lineage cells from the spinal cord of mice induced with experimental autoimmune encephalomyelitis (EAE), which mimics several aspects of MS. We found unique OLs and OL precursor cells (OPCs) in EAE and uncovered several genes specifically alternatively spliced in these cells. Surprisingly, EAE-specific OL lineage populations expressed genes involved in antigen processing and presentation via major histocompatibility complex class I and II (MHC-I and -II), and in immunoprotection, suggesting alternative functions of these cells in a disease context. Importantly, we found that disease-specific oligodendroglia are also present in human MS brains and that a substantial number of genes known to be susceptibility genes for MS, so far mainly associated with immune cells, are expressed in the OL lineage cells. Finally, we demonstrate that OPCs can phagocytose and that MHC-II-expressing OPCs can activate memory and effector CD4-positive T cells. Our results suggest that OLs and OPCs are not passive targets but instead active immunomodulators in MS. The disease-specific OL lineage cells, for which we identify several biomarkers, may represent novel direct targets for immunomodulatory therapeutic approaches in MS

    Novel CTSC mutations in a patient with Papillon-Lefevre syndrome with recurrent pyoderma and minimal oral and palmoplantar involvement

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    SIR, Papillon–Lefe`vre syndrome (PLS) is an autosomal recessivegenodermatosis mainly characterized by early-onset periodontitisand palmoplantar keratoderma. Recurrent pyogenic skininfections, usually of mild degree and self-healing, are relativelycommon additional features.1,2 PLS is caused by lossof-function mutations in the CTSC gene, which encodes forcathepsin C, a lysosomal cysteine protease required forthe activation of granule-associated serine proteases inimmune ⁄inflammatory cells

    In vitro and in silico analysis of the vascular effects of asymmetrical N,N-bis(alkanol)amine aryl esters, novel multidrug resistance-reverting agents

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    9noreservedAsymmetrical N,N-bis(alkanol)amine aryl esters (FRA77, GDE6, and GDE19) are potent multidrug resistance (MDR) reversers. Their structures loosely remind that of the Ca2+ antagonist verapamil. Therefore, the aim of this study was to investigate their vascular activity in vitro. Their effects on the mechanical activity of fresh and cultured rat aorta rings on Cav1.2 channel current (ICa1.2) of A7r5 cells and their cytotoxicity on A7r5 and EA.hy926 cells were analyzed. Docking at the rat α1C subunit of the Cav1.2 channel was simulated in silico. Compounds tested were cytotoxic at concentrations >1 ΌM (FRA77, GDE6, GDE19) and >10 ΌM (verapamil) in EA.hy926 cells, or >10 ΌM (FRA77, GDE6, GDE19) and at 100 ΌM (verapamil) in A7r5 cells. In fresh rings, the three compounds partly antagonized phenylephrine and 60 mM K+ (K60)-induced contraction at concentrations ≄1 and ≄3 ΌM, respectively. On the contrary, verapamil fully relaxed rings pre-contracted with both agents. In cultured rings, 10 ΌM GDE6, GDE19, FRA77, and verapamil significantly reduced the contractile response to both phenylephrine and K60. Similarly to verapamil, the three compounds docked at the α1C subunit, interacting with the same amino acids residues. FRA77, GDE6, and GDE19 inhibited ICa1.2 with IC50 values 1 order of magnitude higher than that of verapamil. FRA77-, GDE6-, and GDE19-induced vascular effects occurred at concentrations that are at least 1 order of magnitude higher than those effectively reverting MDR. Though an unambiguous divergence between MDR reverting and vascular activity is of overwhelming importance, these findings consistently contribute to the design and synthesis of novel and potent chemosensitizers.mixedFusi, Fabio; Durante, Miriam; Spiga, Ottavia; Trezza, Alfonso; Frosini, Maria; Floriddia, E.; Teodori, Elisabetta; Dei, Silvia; Saponara, SimonaFusi, Fabio; Durante, Miriam; Spiga, Ottavia; Trezza, Alfonso; Frosini, Maria; Floriddia, E.; Teodori, Elisabetta; Dei, Silvia; Saponara, Simon
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