Macroautophagy in Dendritic Cells Controls the Homeostasis and Stability of Regulatory T Cells.

Regulatory T cells (Tregs) play a crucial role in controlling autoimmune and inflammatory responses. Recent studies have demonstrated that dendritic cells (DCs) contribute to the homeostasis of peripheral Tregs. Autophagy, a critical pathway for cellular homeostasis, is active in DCs and is upregulated in different inflammatory conditions. We have shown that Tregs are expanded and have phenotypic alterations and impaired suppressive functions in mice with autophagy-deficient DCs. RNA profiling of Tregs revealed that autophagy in DCs is required to stabilize Treg expression signatures. This phenotype is linked to the downregulation of ICOS-Ligand expression in autophagy-deficient DCs, a consequence of the accumulation of ADAM10, the metalloproteinase responsible for its cleavage. Upon inflammation, in antigen-induced arthritis, mice with autophagy-deficient DCs exhibit increased synovial inflammation and cartilage and bone erosion correlating with Treg-to-Th17 conversion. Our data reveal a mechanism that couples autophagy deficiency in DCs to the function, homeostasis, and stability of Tregs

A computational psychiatry approach identifies how alpha-2A noradrenergic agonist Guanfacine affects feature-based reinforcement learning in the macaque

[EN] Noradrenaline is believed to support cognitive flexibility through the alpha 2A noradrenergic receptor (a2A-NAR) acting in prefrontal cortex. Enhanced flexibility has been inferred from improved working memory with the a2A-NA agonist Guanfacine. But it has been unclear whether Guanfacine improves specific attention and learning mechanisms beyond working memory, and whether the drug effects can be formalized computationally to allow single subject predictions. We tested and confirmed these suggestions in a case study with a healthy nonhuman primate performing a feature-based reversal learning task evaluating performance using Bayesian and Reinforcement learning models. In an initial dose-testing phase we found a Guanfacine dose that increased performance accuracy, decreased distractibility and improved learning. In a second experimental phase using only that dose we examined the faster feature-based reversal learning with Guanfacine with single-subject computational modeling. Parameter estimation suggested that improved learning is not accounted for by varying a single reinforcement learning mechanism, but by changing the set of parameter values to higher learning rates and stronger suppression of non-chosen over chosen feature information. These findings provide an important starting point for developing nonhuman primate models to discern the synaptic mechanisms of attention and learning functions within the context of a computational neuropsychiatry framework.This research was supported by grants from the Canadian Institutes of Health Research (CIHR), the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Ontario Ministry of Economic Development and Innovation (MEDI). We thank Dr. Hongying Wang for invaluable help with drug administration and animal careHassani, SA.; Oemisch, M.; Balcarras, M.; Westendorff, S.; Ardid-Ramírez, JS.; Van Der Meer, MA.; Tiesinga, P.... (2017). 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Effects of the alpha-2 adrenoceptor agonist guanfacine on attention and working memory in aged non-human primates. European Journal of Neuroscience 34, 1018–1022 (2011)

Recherche d'un parallélisme entre quelques directions crânio-faciales au cours de l'ontogenèse

For 6 pairs of cranio-facial straight lines the directions have been compared during ontogenesis in order to discover possible parallelisms ; it is proved that the angular differences revealed in that way evolve with time and that the best result is obtained between Na - Pr and S - Ba during the orthodontical period.Pour 6 couples de droites crânio-faciales, les directions ont été comparées, durant l'ontogenèse, afin de rechercher d'éventuels parallélismes. Il s'avère que les différences angulaires ainsi mises en évidence évoluent avec l'âge, et que le meilleur résultat s'obtient entre Na - Pr et S - Ba, dans la période orthodontique.Fenart R., Harlé G., Papernot G. Recherche d'un parallélisme entre quelques directions crânio-faciales au cours de l'ontogenèse. In: Bulletins et Mémoires de la Société d'anthropologie de Paris, XIII° Série. Tome 10 fascicule 2, 1983. pp. 251-257

Expectations and outcome: The role of Proposer features in the Ultimatum Game

In social decision-making individuals make choices in an interactive context and their decisions may therefore be influenced by information they receive about features of the other player. These features may 'frame' the other player in particular ways and generate expectations about the outcome. This research examines the impact of information about the Proposer on the Responder's decision in the Ultimatum Game (UG). Two-hundred and forty undergraduates played the UG after being provided with different descriptions of the Proposer's (no information, physical description, psychological description). The results show that acceptance rates are significantly influenced by both offer fairness as well as the type of description. These results support the relevance of the expectation effects due to the framing in social decision making.Expectations Framing Cognitive dissonance Social decision-making Ultimatum Game

The effect of obstructed action efficacy on reward-based decision-making in healthy adolescents: a novel functional MRI task to assay frustration

Frustration is common in adolescence and often interferes with executive functioning, particularly reward-based decision-making, and yet very little is known about how incidental frustrating events (independent of task-based feedback) disrupt the neural circuitry of reward processing in this important age group. While undergoing functional magnetic resonance imaging (fMRI), 45 healthy adolescents played a card game in which they had to guess between two options to earn points, in low- and high-stake conditions. Functioning of button presses through which they made decisions was intermittently blocked, thereby increasing frustration potential. Neural deactivation of the precuneus, a Default Mode Network region, was observed during obstructed action blocks across stake conditions, but less so on high- relative to low-stake trials. Moreover, less deactivation in goal-directed reward processing regions (i.e., caudate), frontoparietal "task control" regions, and interoceptive processing regions (i.e., somatosensory cortex, thalamus) were observed on high-stake relative to low-stake trials. These findings are consistent with less disruption of goal-directed reward seeking during blocked action efficacy in high-stake conditions among healthy adolescents. These results provide a roadmap of neural systems critical to the processing of frustrating events during reward-based decision-making in youths and could help to characterize how frustration regulation is altered in a range of pediatric psychopathologies

A thermogravimetric and FT-IR study of the reduction by H2 of sulfated Pt/CexZr1-xO2 solids

International audienc

Thermodynamic and experimental studies of catalytic reforming of exhaust gas recirculation in gasoline engines

International audienc

Characteristics of Systemic Sclerosis patients with positive anti-Th/To antibodies: About 6 patients and literature review

International audienceAmong the antibodies described in Systemic Sclerosis (SSc), anti-Th/To antibodies (anti-Th/To) are rare and have been poorly studied. Thus, little is known about the profile of anti-Th/To positive patients. From our local Biobank (Marseille, France), we retrospectively selected data for 6 patients positive for anti-Th/To with an Immunodot assay. All of them suffered from SSc, sharing clinical and biological common features such as a limited cutaneous form of SSc, a decreased lung diffusing capacity and a speckled nuclear nucleolar immunofluorescence pattern of antinuclear antibodies screening on HEp-2 cells. In order to further characterize patients positive for anti-Th/To, we performed a thorough literature review. From 402 studied patients positive for anti-Th/To, we confirmed that these antibodies are associated with the limited cutaneous form of the disease (88% of the patients), and with an SSc related-pulmonary involvement (50%). The review analysis pointed out the rarity of the anti-Th/To with an estimated mean frequency of 3.4% of all SSc patients worldwide, their usual exclusivity with respect to the specific antibodies of scleroderma, and their high specificity (around 98%) for the diagnosis of SSc.Parmi les anticorps décrits associés à la Sclérodermie Systémique (ScS), les anticorps anti-Th/To (anti-Th/To) sont rares et ont été peu étudiés. Ainsi, nous n’avons que peu de connaissance sur le profil des patients positifs pour les anti-Th/To. À partir d’une Biobanque locale (Marseille, France), nous avons sélectionné de façon rétrospective 6 patients positifs pour les anti-Th/To, en test Immunodot. Tous souffraient de ScS et partageaient des caractéristiques cliniques et biologiques communes, comme la forme cutanée limitée de la ScS, une baisse de la diffusion alvéolocapillaire pulmonaire et un aspect moucheté nucléolaire en immunofluorescence indirecte au test de dépistage des anticorps anti-nucléaires sur cellules Hep-2. Afin de caractériser davantage les patients positifs pour les anti-Th/To, nous avons réalisé une revue de la littérature sur le sujet. À partir de l’étude de 402 patients positifs pour les anti-Th/To, nous confirmons que ces anticorps sont principalement associés à la forme cutanée limitée de la maladie (88 % de l’ensemble des patients), et à une atteinte pulmonaire de la ScS (50 % de l’ensemble des patients). Cette analyse de la littérature illustre la rareté des anti-Th/To avec une fréquence moyenne estimée de 3,4 % chez tous les patients souffrant de ScS dans le monde entier, leur caractère habituellement exclusif vis-à-vis des autres autoanticorps spécifiques de la Sclérodermie, ainsi que leur grande spécificité (environ 98 %) pour le diagnostic de la ScS

Increased soluble p55 and p75 tumour necrosis factor-α receptors in patients with hepatitis C-associated mixed cryoglobulinaemia

To investigate whether tumour necrosis factor α (TNFα) plays a role in the pathogenesis of hepatitis C virus-associated mixed cryoglobulinaemia (HCV-MC), we measured soluble TNFα and its soluble p55 (sTNFR1) and p75 (sTNFR2) receptors in the serum of patients with HCV-MC. TNFα, sTNFR1 and sTNFR2 were measured in the serum of 32 patients with HCV-MC, 18 patients with hepatitis C without MC (HCV) and 18 healthy volunteers, using specific immunoassays. Correlations between clinical and biological parameters and the concentrations of TNFα and sTNFRs were established by studying detailed clinical records of the 32 HCV-MC patients. Although higher, TNFα levels were not significantly different in HCV-MC patients compared with healthy or HCV controls. sTNFR1 and sTNFR2, however, were significantly higher in HCV-MC compared with controls or with HCV patients, and higher concentrations of sTNFR1 and sTNFR2 were observed in patients with severe visceral vasculitis, compared with patients with limited purpura. sTNFR1 concentrations positively correlated with fibrinogen levels but TNFα, sTNFR1 and sTNFR2 did not correlate with other biological parameters such as rheumatoid factor concentrations, CH50 or C4 values. These data suggest a role for TNFα in the pathogenesis of the immune complex-mediated vasculitis associated with HCV-MC