Postural Adaptation of the Spatial Reference Frames to Microgravity: Back to the Egocentric Reference Frame

BACKGROUND: In order to test how gravitational information would affect the choice of stable reference frame used to control posture and voluntary movement, we have analysed the forearm stabilisation during sit to stand movement under microgravity condition obtained during parabolic flights. In this study, we hypothesised that in response to the transient loss of graviceptive information, the postural adaptation might involve the use of several strategies of segmental stabilisation, depending on the subject's perceptual typology (dependence--independence with respect to the visual field). More precisely, we expected a continuum of postural strategies across subjects with 1) at one extreme the maintaining of an egocentric reference frame and 2) at the other the re-activation of childhood strategies consisting in adopting an egocentric reference frame. METHODOLOGY/PRINCIPAL FINDINGS: To check this point, a forearm stabilisation task combined with a sit to stand movement was performed with eyes closed by 11 subjects during parabolic flight campaigns. Kinematic data were collected during 1-g and 0-g periods. The postural adaptation to microgravity's constraint may be described as a continuum of strategies ranging from the use of an exo- to an egocentric reference frame for segmental stabilisation. At one extremity, the subjects used systematically an exocentric frame to control each of their body segments independently, as under normogravity conditions. At the other, the segmental stabilisation strategies consist in systematically adopting an egocentric reference frame to control their forearm's stabilisation. A strong correlation between the mode of segmental stabilisation used and the perceptual typology (dependence--independence with respect to the visual field) of the subjects was reported. CONCLUSION: The results of this study show different subjects' typologies from those that use the forearm orientation in a mainly exocentric reference frame to those that use the forearm orientation in a mainly egocentric reference frame

Development of Postural Control in Healthy Children: A Functional Approach

From a set of experimental studies showing how intersegmental coordination develops during childhood in various posturokinetic tasks, we have established a repertoire of equilibrium strategies in the course of ontogenesis. The experimental data demonstrate that the first reference frame used for the organization of balance control during locomotion is the pelvis, especially in young children. Head stabilization during posturokinetic activities, particularly locomotion, constitutes a complex motor skill requiring a long time to develop during childhood. When studying the emergence of postural strategies, it is essential to distinguish between results that can be explained by biomechanical reasons strictly and those reflecting the maturation of the central nervous system (CNS). To address this problem, we have studied our young subjects in situations requiring various types of adaptation. The studies dealing with adaptation of postural strategies aimed at testing short and long-term adaptation capacity of the CNS during imposed transient external biomechanical constraints in healthy children, and during chronic internal constraints in children with skeletal pathologies. In addition to maintenance of balance, another function of posture is to ensure the orientation of a body segment. It appears that the control of orientation and the control of balance both require the trunk as an initial reference frame involving a development from egocentric to exocentric postural control. It is concluded that the first step for children consists in building a repertoire of postural strategies, and the second step consists in learning to select the most appropriate postural strategy, depending on the ability to anticipate the consequence of the movement in order to maintain balance control and the efficiency of the task

Terminal NK cell maturation is controlled by concerted actions of T-bet and Zeb2 and is essential for melanoma rejection

Natural killer (NK) cell maturation is a tightly controlled process that endows NK cells with functional competence and the capacity to recognize target cells. Here, we found that the transcription factor (TF) Zeb2 was the most highly induced TF during NK cell maturation. Zeb2 is known to control epithelial to mesenchymal transition, but its role in immune cells is mostly undefined. Targeted deletion of Zeb2 resulted in impaired NK cell maturation, survival, and exit from the bone marrow. NK cell function was preserved, but mice lacking Zeb2 in NK cells were more susceptible to B16 melanoma lung metastases. Reciprocally, ectopic expression of Zeb2 resulted in a higher frequency of mature NK cells in all organs. Moreover, the immature phenotype of Zeb2(-/-) NK cells closely resembled that of Tbx21(-/-) NK cells. This was caused by both a dependence of Zeb2 expression on T-bet and a probable cooperation of these factors in gene regulation. Transgenic expression of Zeb2 in Tbx21(-/-) NK cells partially restored a normal maturation, establishing that timely induction of Zeb2 by T-bet is an essential event during NK cell differentiation. Finally, this novel transcriptional cascade could also operate in human as T-bet and Zeb2 are similarly regulated in mouse and human NK cells

Conséquences d'une dérégulation de la voie de l'interleukine 1 sur la cytotoxicité des cellules Natural Killer chez la souris et chez l'homme

Les syndromes d activation macrophagique (SAM) sont des désordres auto-immuns dont les causes primaires sont dues à des déficits fonctionnels des cellules cytotoxiques comme les lymphocytes T CD8 et les cellules Natural Killer (NK). Ces SAM compliquent également des maladies auto-inflammatoires comme les arthrites juvéniles systémiques idiopathiques (SoJIA), sans que le mécanisme physiopathologique ne soit connu. Comme les autres maladies auto-inflammatoires, ces arthrites se caractérisent par une dérégulation de l immunité innée, telle que la voie de l interleukine 1 (IL-1). Dans un premier temps, nous avons synthétisé les données existantes sur la physiopathologie des SAM dans ses formes familiales d une part, et d autre part, dans ses formes liées au SoJIA et étudié l implication de la dérégulation de la voie de l IL-1 observée dans la SoJIA, dans le développement des SAM. Dans un deuxième temps, nous avons exploré la cytotoxicité de manière globale, en nous concentrant sur les cellules NK, dans un modèle murin de dérégulation de la voie de l IL-1, les souris Il-1 RA KO. Ces souris sont, en effet, déficientes en IL-1 RA, un antagoniste physiologique de l IL-1 et sont donc surexposées à l IL-1 endogène. Enfin, nous avons également étudié la fonctionnalité des cellules NK chez 4 patients atteints de SoJIA. Les résultats obtenus suggèrent que, dans ce modèle, une dérégulation de l IL-1 ne perturbe pas la distribution, le phénotype et la fonction des cellules NK, ni n aggrave les SAM induits par injection de ligands des Toll-Like Receptors. De plus, les patients atteints de SoJIA n ont pas de défaut intrinsèque de cytotoxicitéLYON1-BU Santé (693882101) / SudocSudocFranceF

Adolescence: A Transient Period of Proprioceptive Neglect in Sensory Integration of Postural Control

International audienc

Rigorous Design of Cyber-Physical Systems: Linking Physicality and Computation

International audienceCyber-physical systems have developed into a very active research field, with a broad range of challenges and research directions going from requirements, to implementation and simulation, as well as validation and verification to guarantee essential properties. In this survey paper, we focus exclusively on the following fundamental issue: how to link physicality and computation, continuous time-space dynamics with discrete untimed ones? We consider that cyber-physical system design flow involves the following three main steps: 1) cyber-physical systems modeling; 2) discretization for executability; and 3) simulation and implementation. We review—and strive to provide insight into possible approaches for addressing—the key issues, for each of these three steps

One-Year Follow-Up of Natural Killer Cell Activity in Multiple Myeloma Patients Treated With Adjuvant Lenalidomide Therapy

Multiple myeloma (MM) is a proliferation of tumoral plasma B cells that is still incurable. Natural killer (NK) cells can recognize and kill MM cells in vitro and can limit MM growth in vivo. Previous reports have shown that NK cell function is impaired during MM progression and suggested that treatment with immunomodulatory drugs (IMIDs) such as lenalidomide (LEN) could enhance it. However, the effects of IMIDs on NK cells have been tested mostly in vitro or in preclinical models and supporting evidence of their effect in vivo in patients is lacking. Here, we monitored NK cell activity in blood samples from 10 MM patients starting after frontline induction chemotherapy (CTX) consisting either of association of bortezomib–lenalidomide–dexamethasone (Velcade Revlimid Dexamethasone) or autologous stem-cell transplantation (SCT). We also monitored NK cell activity longitudinally each month during 1 year, after maintenance therapy with LEN. Following frontline chemotherapy, peripheral NK cells displayed a very immature phenotype and retained poor reactivity toward target cells ex vivo. Upon maintenance treatment with LEN, we observed a progressive normalization of NK cell maturation, likely caused by discontinuation of chemotherapy. However, LEN treatment neither activated NK cells nor improved their capacity to degranulate or to secrete IFN-γ or MIP1-β following stimulation with MHC-I-deficient or antibody-coated target cells. Upon LEN discontinuation, there was no reduction of NK cell effector function either. These results caution against the use of LEN as single therapy to improve NK cell activity in patients with cancer and call for more preclinical assessments of the potential of IMIDs in NK cell activation