The manual haptic perception of orientations and the oblique effect in patients with left visuo-spatial neglect.

International audienceThis study addresses the limits of haptic orientation deficit observed in patients with left visuo-spatial neglect (VSN) in the fronto-parallel plane. We concentrated on two aspects of the haptic perception of vertical, horizontal and oblique orientations: first, the global level of performances compared with normal subjects and, second, the occurrence of the oblique effect (i.e. lower performances in oblique orientations than in vertical-horizontal orientations). Subjects were asked to position a rod, presented in the fronto-parallel plane, to one of four orientations: vertical, horizontal, left 45 degrees oblique and right 45 degrees oblique. First, we found a haptic orientation deficit in neglect patients: The precision was lower in the neglect patients than in the normal (young adults and seniors) subjects. Second, we observed in both neglect patients and control subjects the occurrence of a similar haptic oblique effect and there were no differences between the results in the left and right hemispaces. Taken together, this means that, in spite of the global haptic orientation production deficit observed in VSN patients, no specific pattern was observed in the haptic production of different orientations in these subjects as compared to the two other groups. The haptic orientation deficit of neglect patients seems to affect in the same way all values and spatial positions of orientations

La détection des évènements rares

International audienc

La détection des évènements rares

International audienc

Decision-Making in a Changing World: A Study in Autism Spectrum Disorders

International audienceTo learn to deal with the unexpected is essential to adaptation to a social, therefore often unpredictable environment. Fourteen adults with Autism Spectrum Disorders (ASD) and 15 controls underwent a decision-making task aimed at investigating the influence of either a social or a non-social environment, and its interaction with either a stable (with constant probabilities) or an unstable (with changing probabilities) context on their performance. Participants with ASD presented with difficulties in accessing underlying statistical rules in an unstable context, a deficit especially enhanced in the social environment. These results point out that the difficulties people with ASD encounter in their social life might be caused by impaired social cues processing and by the unpredictability associated with the social world

The French Version of the DABS: Adaptation Process and Preliminary Field Test

International audienceThe aim of this study was to develop a transcultural adaptation of the Diagnostic Adaptive Behavior Scale (DABS) in French and to perform a field evaluation of the adapted version of the tool (DABS-F). Eight experts in intellectual and developmental disabilities (IDD) and two professional translators formed two committees to translate the instrument. Thirty-four independent experts in IDD rated the clarity and relevance of the DABS-F. Results indicated complete agreement between the two translation committees and also demonstrated very satisfactory levels of clarity and relevance for the DABS-F. The latter result can be considered as evidence of the content validity of the adapted tool. Adjustments for the few items that presented less satisfactory results are discussed

p65/RelA NF‐κB fragments generated by RIPK3 activity regulate tumorigenicity, cell metabolism, and stemness characteristics

International audienc

image_1_Natural Killer Cells Regulate Th17 Cells After Autologous Hematopoietic Stem Cell Transplantation for Relapsing Remitting Multiple Sclerosis.tif

<p>In autoimmunity, the balance of different helper T (Th) cell subsets can influence the tissue damage caused by autoreactive T cells. Pro-inflammatory Th1 and Th17 T cells are implicated as mediators of several human autoimmune conditions such as multiple sclerosis (MS). Autologous hematopoietic stem cell transplantation (aHSCT) has been tested in phase 2 clinical trials for MS patients with aggressive disease. Abrogation of new clinical relapses and brain lesions can be seen after ablative aHSCT, accompanied by significant reductions in Th17, but not Th1, cell populations and activity. The cause of this selective decrease in Th17 cell responses following ablative aHSCT is not completely understood. We identified an increase in the kinetics of natural killer (NK) cell reconstitution, relative to CD4⁺ T cells, in MS patients post-aHSCT, resulting in an increased NK cell:CD4⁺ T cell ratio that correlated with the degree of decrease in Th17 responses. Ex vivo removal of NK cells from post-aHSCT peripheral blood mononuclear cells resulted in higher Th17 cell responses, indicating that NK cells can regulate Th17 activity. NK cells were also found to be cytotoxic to memory Th17 cells, and this toxicity is mediated through NKG2D-dependent necrosis. Surprisingly, NK cells induced memory T cells to secrete more IL-17A. This was preceded by an early rise in T cell expression of RORC and IL17A mRNA, and could be blocked with neutralizing antibodies against CD58, a costimulatory receptor expressed on NK cells. Thus, NK cells provide initial co-stimulation that supports the induction of a Th17 response, followed by NKG2D-dependent cytotoxicity that limits these cells. Together these data suggest that rapid reconstitution of NK cells following aHSCT contribute to the suppression of the re-emergence of Th17 cells. This highlights the importance of NK cells in shaping the reconstituting immune system following aHSCT in MS patients.</p

Natural Killer Cells Regulate Th17 Cells After Autologous Hematopoietic Stem Cell Transplantation for Relapsing Remitting Multiple Sclerosis

In autoimmunity, the balance of different helper T (Th) cell subsets can influence the tissue damage caused by autoreactive T cells. Pro-inflammatory Th1 and Th17 T cells are implicated as mediators of several human autoimmune conditions such as multiple sclerosis (MS). Autologous hematopoietic stem cell transplantation (aHSCT) has been tested in phase 2 clinical trials for MS patients with aggressive disease. Abrogation of new clinical relapses and brain lesions can be seen after ablative aHSCT, accompanied by significant reductions in Th17, but not Th1, cell populations and activity. The cause of this selective decrease in Th17 cell responses following ablative aHSCT is not completely understood. We identified an increase in the kinetics of natural killer (NK) cell reconstitution, relative to CD4+ T cells, in MS patients post-aHSCT, resulting in an increased NK cell:CD4+ T cell ratio that correlated with the degree of decrease in Th17 responses. Ex vivo removal of NK cells from post-aHSCT peripheral blood mononuclear cells resulted in higher Th17 cell responses, indicating that NK cells can regulate Th17 activity. NK cells were also found to be cytotoxic to memory Th17 cells, and this toxicity is mediated through NKG2D-dependent necrosis. Surprisingly, NK cells induced memory T cells to secrete more IL-17A. This was preceded by an early rise in T cell expression of RORC and IL17A mRNA, and could be blocked with neutralizing antibodies against CD58, a costimulatory receptor expressed on NK cells. Thus, NK cells provide initial co-stimulation that supports the induction of a Th17 response, followed by NKG2D-dependent cytotoxicity that limits these cells. Together these data suggest that rapid reconstitution of NK cells following aHSCT contribute to the suppression of the re-emergence of Th17 cells. This highlights the importance of NK cells in shaping the reconstituting immune system following aHSCT in MS patients

Involvement of ORAI1/SOCE in Human AML Cell Lines and Primary Cells According to ABCB1 Activity, LSC Compartment and Potential Resistance to Ara-C Exposure

International audienceAcute myeloid leukemia (AML) is a hematological malignancy with a high risk of relapse. This issue is associated with the development of mechanisms leading to drug resistance that are not yet fully understood. In this context, we previously showed the clinical significance of the ATP binding cassette subfamily B-member 1 (ABCB1) in AML patients, namely its association with stemness markers and an overall worth prognosis. Calcium signaling dysregulations affect numerous cellular functions and are associated with the development of the hallmarks of cancer. However, in AML, calcium-dependent signaling pathways remain poorly investigated. With this study, we show the involvement of the ORAI1 calcium channel in store-operated calcium entry (SOCE), the main calcium entry pathway in non-excitable cells, in two representative human AML cell lines (KG1 and U937) and in primary cells isolated from patients. Moreover, our data suggest that in these models, SOCE varies according to the differentiation status, ABCB1 activity level and leukemic stem cell (LSC) proportion. Finally, we present evidence that ORAI1 expression and SOCE amplitude are modulated during the establishment of an apoptosis resistance phenotype elicited by the chemotherapeutic drug Ara-C. Our results therefore suggest ORAI1/SOCE as potential markers of AML progression and drug resistance apparition