How about running on Mars? Influence of sensorimotor coherence on running and spatial perception in simulated reduced gravity

Motor control, including locomotion, strongly depends on the gravitational field. Recent developments such as lower-body positive pressure treadmills (LBPPT) have enabled studies on Earth about the effects of reduced body weight (BW) on walking and running, up to 60% BW. The present experiment was set up to further investigate adaptations to a more naturalistic simulated hypogravity, mimicking a Martian environment with additional visual information during running sessions on LBPPT. Twenty-nine participants performed three sessions of four successive five-min runs at preferred speed, alternating Earth- or simulated Mars-like gravity (100% vs. 38% BW). They were displayed visual scenes using a virtual reality headset to assess the effects of coherent visual flow while running. Running performance was characterized by normal ground reaction force and pelvic accelerations. The perceived upright and vection (visually-induced self-motion sensation)in dynamic visual environments were also investigated at the end of the different sessions. We found that BW reduction induced biomechanical adaptations independently of the visual context. Active peak force and stance time decreased, while flight time increased. Strong inter-individual differences in braking and push-off times appeared at 38% BW, which were not systematically observed in our previous studies at 80% and 60% BW. Additionally, the importance given to dynamic visual cues in the perceived upright diminished at 38% BW, suggesting an increased reliance on the egocentric body axis as a reference for verticality when the visual context is fully coherent with the previous locomotor activity. Also, while vection was found to decrease in case of a coherent visuomotor coupling at 100% BW (i.e., post-exposure influence), it remained unaffected by the visual context at 38% BW. Overall, our findings suggested that locomotor and perceptual adaptations were not similarly impacted, depending on the -simulated- gravity condition and visual context

Inherited Human ITK Deficiency Impairs IFN-γ Immunity and Underlies Tuberculosis

Inborn errors of IFN-γ immunity can underlie tuberculosis (TB). We report three patients from two kindreds without EBV viremia or disease but with severe TB and inherited complete ITK deficiency, a condition associated with severe EBV disease that renders immunological studies challenging. They have CD4+ αβ T lymphocytopenia with a concomitant expansion of CD4-CD8- double-negative (DN) αβ and Vδ2- γδ T lymphocytes, both displaying a unique CD38+CD45RA+T-bet+EOMES- phenotype. Itk-deficient mice recapitulated an expansion of the γδ T and DN αβ T lymphocyte populations in the thymus and spleen, respectively. Moreover, the patients\u27 T lymphocytes secrete small amounts of IFN-γ in response to TCR crosslinking, mitogens, or forced synapse formation with autologous B lymphocytes. Finally, the patients\u27 total lymphocytes secrete small amounts of IFN-γ, and CD4+, CD8+, DN αβ T, Vδ2+ γδ T, and MAIT cells display impaired IFN-γ production in response to BCG. Inherited ITK deficiency undermines the development and function of various IFN-γ-producing T cell subsets, thereby underlying TB

Pensar as crises

Revue de l'Université pontificale catholique (PUC) de São Paulo (Brésil)International audienceThe purpose of this article, by Antoine Casanova and Rémy Herrera, is to provide a series of materials to the readers in order to understand the current crisis, to be considered as a systemic one, and in the perspective of “long duration” stepping over crises of “old type” and “mixed” crises that preceded those of modern capitalism. As a matter of fact, the question of our time is that of the “refeudalisation of the world.”Fornecer ao leitor material para compreender a crise atual, enquanto crise sistêmica e na perspectiva de “longa duração”. As crises, “de tipos antigo” e “mistas”, que precederam as do capitalismo moderno, são aqui objeto de análise, pois os autores partem da ideia de que a questão de nossa época é a da “refeudalização do mundo”. Palavras-chave: crise sistêmica; capitalismo; história econômica

Régénération osseuse (caractérisation biomécanique et bio-prothèse)

Le premier objectif de notre travail est de caractériser l'évolution temporelle de proprié-tés structurales et mécaniques de matériau osseux régénéré et immature sur un grand volume.Nous avons étudié ce tissu en évolution lors de sa genèse dans un environnement mécanique contrôlé. Pour caractériser l'évolution temporelle des propriétés mécaniques de ce tissu, à partir d'un modèle animal, nous mettons en place une étude couplant essais mécanique d'indentation,observations macroscopiques et étude histologique. Cette méthodologie combinée donne des informations complémentaires à différentes échelles : macroscopique par simple observation,mésoscopique avec les tests d'indentation et microscopique avec l'histologie. Le tissu osseux ré-généré évolue d'un matériau homogène, visqueux et souple vers un matériau hétérogènes, plus rigide et moins visqueux. D'un point de vue biologique, l'organisation cellulaire part d'un amas de nombreuses cellules et progresse vers une structure plus proche de celle de l'os. Mécanique et biologie révèlent une évolution similaire : d'abord le régénérat grossit, puis il se différencie en tissu ostéochondral et finalement, la calcification commence. Les résultats biologiques confirment les études de la littérature et les résultats mécaniques donnent les premières valeurs de caractéristiques mécaniques de ce tissu avec le module d'Young réduit.Le deuxième objectif de cette étude est de développer une bioprothèse avec un biomatériau biodegradebable afin de régénérer un défaut d'os de taille critique. Notre étude est originale carelle propose d'utiliser le biomatériau comme tuteur de la régénération. Une étude préliminaire a été menée avec un modèle animal et un biomatériau céramique phosphocalcique. De premiers résultats encourageant ont été obtenus mais le processus clinique reste à concrétiser.The first objective of our work was to experimentally characterise the temporal evolutionof the structural and mechanical properties of large volume immature regenerated tissues. Westudied these evolving tissues from their genesis in controlled mechanical conditions. To characterizethe temporal evolution of mechanical properties, based on animal model, we carried outindentation tests coupled with macroscopic examinations and histological studies. This combinedmethodology yielded a range of information on osteogenesis at different scales : macroscopic bysimple observation, mesoscopic by indentation test and microscopic by histological study. Resultsallowed us to identify different periods, providing a link between biological changes and materialproperty evolution in bone tissue regeneration. The regenerated tissue evolves from a viscous,homogeneous, soft material to a heterogeneous stiffer material endowed with a lower viscosity.From a biological point of view, cell organization progresses from a proliferated cell clot to a maturestructure closer to that of the bone. During the first seven days, mechanical and biologicalresults revealed the same evolution : first, the regenerated tissue grew, then, differentiated into anosteochondral tissue and finally calcification began. While our biological results confirm those ofother studies, our mechanical results provide the first experimental mechanical characterizationby reduced Young's modulus of such tissue.In a second time,we develop a bioprothesis with a biodegradebable biomaterial to regenerate acritical size bone defect. Our study is original because it proposes to use the biomaterial to initiatethe regeneration. A study was performed with an animal model and phosphocalcic ceramic.First observation gave some encouraging results but the clinical process should be realizedAIX-MARSEILLE2-Bib.electronique (130559901) / SudocSudocFranceF

Dynamique des ajustements neuromusculaires à la réduction progressive des forces externes

International audienceINTRODUCTION:Previous studies have investigated the running pattern adjustments to sudden perturbations, such as unexpected changes in terrain stiffness or height (1). Interestingly, lower body positive pressure treadmills (LBPPTs) allow for progressive unweighting. During the transition phase, positive correlations have been reported between changes in braking force and changes in vasti and soleus muscle activity (2). However, these correlations were not examined separately for each participant, likely masking inter-individual variability. The current study investigated the dynamics of neuromuscular adjustments to the progressive reduction of external forces, using an individualised analysis. METHODS:Forty men (19±1yr) ran on a LBPPT in 3 consecutive conditions performed at 100, 60 and 100% body weight. The analysis focused on the unweighing transition which included 18±3 right strides. Normal ground reaction force and surface EMG activity of 11 right lower limb muscles were averaged over the braking phase and normalised to their mean value recorded at 100% body weight. Spearman’s correlation tests were used to quantify the relationship between the normalized mean braking force and mean EMG activity. Chi-squared tests were used to compare the proportions of positive and negative significant correlations. RESULTS:Braking force was positively correlated with VM (ρ=0.67±0.11), VL (0.66±0.10) and RF (0.68±0.10) activity in 65, 60 and 63% of the participants, respectively. It was negatively correlated with STSM (-0.67±0.10) and BF (-0.68±0.10) activity in 50 and 28% of them. Braking force was positively correlated with shank muscle activity in few participants (<13%), but negatively correlated with SOL (-0.59±0.13), GaM (-0.58±0.15), GaL (-0.70±0.15), TA (-0.59±0.10) and PL (-0.63±0.10) activity in 8, 13, 28, 23 and 25% of them. Positive correlations predominated for the quadriceps (VM: X²=26, VL: 21.2, RF:25, p<.001), whereas negative correlations predominated for the hamstrings (STSM: X²=20, BF:20, p<.001) and three shank muscles (GaL: X²=6.4, TA: 6.2, PL: 3.8, p<.05).CONCLUSION:The progressive reduction of external forces mainly affected thigh muscle activity. It showed a decrease in quadriceps activity, as previously reported (2), but an increase in hamstring activity in most participants. Operating in the optimal range of their force-length relationship, the hamstrings may have contributed to the reduced peak knee flexion during the stance phase (3). On the other hand, unweighting resulted in opposite adjustments in shank muscle activity between participants. Nevertheless, their activity increased in most of them, suggesting an increased ankle stabilisation. This is attributed to the shift towards a more forefoot strike pattern (3). This adjustment appears to be transient as it is no longer observed after 3 minutes of unweighted running (4).REFERENCES:(1)Daley, in Understanding Mammalian Locomotion, 2016(2)Sainton et al., PloS One, 2016(3)Neal et al., J Orthop Sports Phys Ther, 2016(4)Fazzari et al., Front Physiol, 202

Non-internalizing antibody-drug conjugates display potent anti-cancer activity upon proteolytic release of monomethyl auristatin E in the subendothelial extracellular matrix

Antibody-drug conjugates (ADCs) represent a promising class of biopharmaceuticals with the potential to localize at the tumor site and improve the therapeutic index of cytotoxic drugs. While it is generally believed that ADCs need to be internalized into tumor cells in order to display optimal therapeutic activity, it has recently been shown that non-internalizing antibodies can efficiently liberate disulfide-linked drugs at the extracellular tumor site, leading to potent anti-cancer activity in preclinical animal models. Here, we show that engineered variants of the F16 antibody, specific to a splice isoform of tenascin-C, selectively localize to the subendothelial tumor extracellular matrix in three mouse models of human cancer (U87, A431, MDA-MB-231). A site-specific coupling of F16 in IgG format with a monomethyl auristatin E (MMAE) derivative, featuring a valine-citrulline dipeptide linker equipped with a self-immolative spacer, yielded an ADC product, which cured tumor-bearing mice at a dose of 7 mg/Kg. The observation of an efficient extracellular proteolytic cleavage of the valine-citrulline linker was surprising, as it has generally been assumed that this peptidic structure would be selectively cleaved by cathepsin B in intracellular compartments. The products described in this article may be useful for the treatment of human malignancies, as their cognate antigen is strongly expressed in the majority of human solid tumors, lymphomas and aggressive leukemias, while being virtually undetectable in most normal adult tissues

Prospective Control in Catching: The Persistent Angle-of- Approach Effect in Lateral Interception

International audienceIn lateral interception tasks balls converging onto the same interception location via different trajectories give rise to systematic differences in the kinematics of hand movement. While it is generally accepted that this angle-of-approach effect reflects the prospective (on-line) control of movement, controversy exists with respect to the information used to guide the hand to the future interception location. Based on the pattern of errors observed in a task requiring visual extrapolation of line segments to their intersection with a second line, angle-of-approach effects in lateral interception have been argued to result from perceptual biases in the detection of information about the ball's future passing distance along the axis of hand movement. Here we demonstrate that this account does not hold under experimental scrutiny: The angle-of-approach effect still emerged when participants intercepted balls moving along trajectories characterized by a zero perceptual bias with respect to the ball's future arrival position (Experiment 4). Designing and validating such bias-controlled trajectories were done using the line-intersection extrapolation task (Experiments 2 and 3). The experimental setup used in the present series of experiments was first validated for the lateral interception and the line-intersection extrapolation tasks: In Experiment 1 we used rectilinear ball trajectories to replicate the angle-of-approach effect in lateral interception of virtual balls. Using line segments extracted from these rectilinear ball trajectories, in Experiment 2 we replicated the reported pattern of errors in the estimated locus of intersection with the axis of hand movement. We used these errors to develop a set of bias-free trajectories. Experiment 3 confirmed that the perceptual biases had been corrected for successfully. We discuss the implications on the information-based regulation of hand movement of our finding that the angle-of-approach effect in lateral interception cannot not explained by perceptual biases in information about the ball's future passing distance

Étude de l'impact du genre et de l'attitude sociale de l'audience virtuelle sur un locuteur humain

International audiencePublic speaking anxiety is a common social phobia in the general population, particularly among young adults. This social skill is essential for professional integration. However, few solutions have been developed to train people in public speaking. The research has shown that Virtual Reality tools can be used to improve public speaking performance. To vary the difficulty of the training, virtual audiences expressing different social attitudes may be simulated. However, only few research works have explored the impact of audience's gender on the user experience. In this article, we propose to investigate the impact of simulated social attitudes and of the gender of the virtual audience on subjective measures reflecting the user experience during a public speaking task. We describe an experimental study in which 41 participants were asked to speak in front of a virtual audience with a neutral, positive or negative social attitude. The gender of the virtual audience varied: only males, only females, or mixed-gender agents. After each speech, users assessed the audience's attitudes, self-report their emotions and their ease of public speaking in front of the audience. The results reveal that an audience with a positive attitude and composed of at least one female virtual agent is perceived as more positive and induces more positive emotions.L'anxiété liée à la prise de parole en public est une phobie sociale fréquente dans la population générale, en particulier chez les jeunes adultes. Cette compétence sociale est essentielle pour l'intégration professionnelle. Cependant, peu de solutions ont été développées pour former les personnes à la prise de parole en public. La recherche a montré que les outils de réalité virtuelle peuvent être utilisés pour améliorer la prise de parole en public. Pour varier la difficulté de la formation, une audience virtuelle exprimant différentes attitudes sociales peut être simulée. Cependant, seuls quelques travaux de recherche ont exploré l'impact du sexe de l'audience sur l'expérience de l'utilisateur. Dans cet article, nous proposons d'étudier l'impact des attitudes sociales simulées et du sexe du public virtuel sur les mesures subjectives reflétant l'expérience utilisateur au cours d'une tache de prise de parole en public. Nous décrivons une étude expérimentale dans laquelle 41 participants ont été invités à parler devant un public virtuel composé de deux personnages avec une attitude sociale neutre, positive ou négative. Le sexe de l'audience virtuelle variait : uniquement des hommes, uniquement des femmes ou une audience mixte. Après chaque discours, les utilisateurs ont évalué l'attitude de l'audience, ont fait part de leurs émotions et de leur aisance à parler en public devant l'audience. Les résultats révèlent qu'un public ayant une attitude positive et composé d'au moins un agent virtuel féminin est perçu comme plus positif et engendre plus d'émotions positives