Contradictory information flow in networks with trust and distrust

We offer a proof system and a NetLogo simulation for trust and distrust in networks where contradictory information is shared by ranked lazy and sceptic agents. Trust and its negative are defined as properties of edges: the former is required when a message is passed bottom-up in the hierarchy or received by a sceptic agent; the latter is attributed to channels that require contradiction resolution, or whose terminal is a lazy agent. These procedures are associated with epistemic costs, respectively for confirmation and refutation. We describe the logic, illustrate the algorithms implemented in the model and then focus on experimental results concerning the analysis of epistemic costs, the role of the agents’ epistemic attitude on distrust distribution and the influence of (dis)trust in reaching consensus

Modulation of DNA repair genes induced by TLR9 agonists: A strategy to eliminate “altered” cells?

We provided evidence that the TLR9 engagement of innate immune cells present in the tumor microenvironment by CpG-oligodeoxynucleotide (CpG-ODN) induces down-modulation of DNA repair gene expression in tumor cells, sensitizing cancer cells to DNA-damaging chemotherapy. These findings expand the benefits of CpG-ODN therapy beyond induction of a strong immune response

Differences between kinematic synergies and muscle synergies during two-digit grasping

International audienceThe large number of mechanical degrees of freedom of the hand is not fully exploited during actual movements such as grasping. Usually, angular movements in various joints tend to be coupled, and EMG activities in different hand muscles tend to be correlated. The occurrence of covariation in the former was termed kinematic synergies, in the latter muscle synergies. This study addresses two questions: (i) Whether kinematic and muscle synergies can simultaneously accommodate for kinematic and kinetic constraints. (ii) If so, whether there is an interrelation between kinematic and muscle synergies. We used a reach-grasp-and-pull paradigm and recorded the hand kinematics as well as eight surface EMGs. Subjects had to either perform a precision grip or side grip and had to modify their grip force in order to displace an object against a low or high load. The analysis was subdivided into three epochs: reach, grasp-and-pull, and static hold. Principal component analysis (PCA, temporal or static) was performed separately for all three epochs, in the kinematic and in the EMG domain. PCA revealed that (i) Kinematic-and muscle-synergies can simultaneously accommodate kinematic (grip type) and kinetic task constraints (load condition). (ii) Upcoming grip and load conditions of the grasp are represented in kinematic-and muscle-synergies already during reach. Phase plane plots of the principal muscle-synergy against the principal kinematic synergy revealed (iii) that the muscle-synergy is linked (correlated, and in phase advance) to the kinematic synergy during reach and during grasp-and-pull. Furthermore (iv), pair-wise correlations of EMGs during hold suggest that muscle-synergies are (in part) implemented by coactivation of muscles through common input. Together, these results suggest that kinematic synergies have (at least in part) their origin not just in muscular activation, but in synergistic muscle activation. In short: kinematic synergies may result from muscle synergies

How Tilting the Head Interferes With Eye-Hand Coordination: The Role of Gravity in Visuo-Proprioceptive, Cross-Modal Sensory Transformations

To correctly position the hand with respect to the spatial location and orientation of an object to be reached/grasped, visual information about the target and proprioceptive information from the hand must be compared. Since visual and proprioceptive sensory modalities are inherently encoded in a retinal and musculo-skeletal reference frame, respectively, this comparison requires cross-modal sensory transformations. Previous studies have shown that lateral tilts of the head interfere with the visuo-proprioceptive transformations. It is unclear, however, whether this phenomenon is related to the neck flexion or to the head-gravity misalignment. To answer to this question, we performed three virtual reality experiments in which we compared a grasping-like movement with lateral neck flexions executed in an upright seated position and while lying supine. In the main experiment, the task requires cross-modal transformations, because the target information is visually acquired, and the hand is sensed through proprioception only. In the other two control experiments, the task is unimodal, because both target and hand are sensed through one, and the same, sensory channel (vision and proprioception, respectively), and, hence, cross-modal processing is unnecessary. The results show that lateral neck flexions have considerably different effects in the seated and supine posture, but only for the cross-modal task. More precisely, the subjects’ response variability and the importance associated to the visual encoding of the information significantly increased when supine. We show that these findings are consistent with the idea that head-gravity misalignment interferes with the visuo-proprioceptive cross-modal processing. Indeed, the principle of statistical optimality in multisensory integration predicts the observed results if the noise associated to the visuo-proprioceptive transformations is assumed to be affected by gravitational signals, and not by neck proprioceptive signals per se. This finding is also consistent with the observation of otolithic projections in the posterior parietal cortex, which is involved in the visuo-proprioceptive processing. Altogether these findings represent a clear evidence of the theorized central role of gravity in spatial perception. More precisely, otolithic signals would contribute to reciprocally align the reference frames in which the available sensory information can be encoded.This work was supported by the Centre National d’Etudes Spatiales (DAR 2017/4800000906, DAR 2018/4800000948, 2019/4800001041). JB-E was supported by a Ph.D. fellowship of the École Doctorale Cerveau-Cognition-Comportement (ED3C, n°158, Sorbonne Université and Université de Paris). The research team is supported by the Centre National de la Recherche Scientifique and the Université de Paris. This study contributes to the IdEx Université de Paris ANR-18-IDEX-0001

No Gain No Pain: Relations Between Vestibulo-Ocular Reflexes and Motion Sickness in Mice

Motion sickness occurs when the vestibular system is subjected to conflicting sensory information or overstimulation. Despite the lack of knowledge about the actual underlying mechanisms, several drugs, among which scopolamine, are known to prevent or alleviate the symptoms. Here, we aim at better understanding how motion sickness affects the vestibular system, as well as how scopolamine prevents motion sickness at the behavioral and cellular levels. We induced motion sickness in adult mice and tested the vestibulo-ocular responses to specific stimulations of the semi-circular canals and of the otoliths, with or without scopolamine, as well as the effects of scopolamine and muscarine on central vestibular neurons recorded on brainstem slices. We found that both motion sickness and scopolamine decrease the efficacy of the vestibulo-ocular reflexes and propose that this decrease in efficacy might be a protective mechanism to prevent later occurrences of motion sickness. To test this hypothesis, we used a behavioral paradigm based on visuo-vestibular interactions which reduces the efficacy of the vestibulo-ocular reflexes. This paradigm also offers protection against motion sickness, without requiring any drug. At the cellular level, we find that depending on the neuron, scopolamine can have opposite effects on the polarization level and firing frequency, indicating the presence of at least two types of muscarinic receptors in the medial vestibular nucleus. The present results set the basis for future studies of motion sickness counter-measures in the mouse model and offers translational perspectives for improving the treatment of affected patients

Multisensory gaze stabilization in response to subchronic alteration of vestibular type I hair cells

The functional complementarity of the vestibulo-ocular reflex (VOR) and optokinetic reflex (OKR) allows for optimal combined gaze stabilization responses (CGR) in light. While sensory substitution has been reported following complete vestibular loss, the capacity of the central vestibular system to compensate for partial peripheral vestibular loss remains to be determined. Here, we first demonstrate the efficacy of a 6-week subchronic ototoxic protocol in inducing transient and partial vestibular loss which equally affects the canal- and otolith-dependent VORs. Immunostaining of hair cells in the vestibular sensory epithelia revealed that organ-specific alteration of type I, but not type II, hair cells correlates with functional impairments. The decrease in VOR performance is paralleled with an increase in the gain of the OKR occurring in a specific range of frequencies where VOR normally dominates gaze stabilization, compatible with a sensory substitution process. Comparison of unimodal OKR or VOR versus bimodal CGR revealed that visuo-vestibular interactions remain reduced despite a significant recovery in the VOR. Modeling and sweep-based analysis revealed that the differential capacity to optimally combine OKR and VOR correlates with the reproducibility of the VOR responses. Overall, these results shed light on the multisensory reweighting occurring in pathologies with fluctuating peripheral vestibular malfunction

Streptococcus pneumoniae colonisation in children and adolescents with asthma: Impact of the heptavalent pneumococcal conjugate vaccine and evaluation of potential effect of thirteen-valent pneumococcal conjugate vaccine

none14noBackground: The main aim of this study was to evaluate Streptococcus pneumoniae carriage in a group of school-aged children and adolescents with asthma because these results might indicate the theoretical risk of invasive pneumococcal disease (IPD) of such patients and the potential protective efficacy of the 13-valent pneumococcal conjugate vaccine (PCV13). Methods: Oropharyngeal samples were obtained from 423 children with documented asthma (300 males, 70.9 %), and tested for the autolysin-A-encoding (lytA) and the wzg (cpsA) gene of S. pneumoniae by means of real-time polymerase chain reaction. Results: S. pneumoniae was identified in the swabs of 192 subjects (45.4 %): 48.4 % of whom were aged = 15 years (p < 0.001). Carriage was significantly less frequent among the children who had received recent antibiotic therapy (odds ratio [OR 0.41]; 95 % confidence interval [95 % CI] 0.22-0.76). Multivariate analyses showed no association between carriage and vaccination status, with ORs of 1.05 (95 % CI 0.70-1.58) for carriers of any pneumococcal serotype, 1.08 (95 % CI 0.72-1.62) for carriers of any of the serotypes included in 7-valent pneumococcal conjugate vaccine (PCV7), and 0.76 (95 % CI 0.45-1.28) for carriers of any of the six additional serotypes of PCV13. Serotypes 19 F, 4 and 9 V were the most frequently identified serotypes in vaccinated subjects. Conclusions: These results showed that carriage of S. pneumoniae is relatively common in all school-aged children and adolescents with asthma, regardless of the severity of disease and the administration of PCV7 in the first years of life. This highlights the problem of the duration of the protection against colonisation provided by pneumococcal conjugate vaccine, and the importance of re-colonization by the same pneumococcal serotypes included in the previously used vaccine.Esposito, Susanna; Terranova, Leonardo; Patria, Maria Francesca; Marseglia, Gian Luigi; Miraglia del Giudice, Michele; Bodini, Alessandro; Martelli, Alberto; Baraldi, Eugenio; Mazzina, Oscar; Tagliabue, Claudia; Licari, Amelia; Ierardi, Valentina; Lelii, Mara; Principi, NicolaEsposito, Susanna; Terranova, Leonardo; Patria, Maria Francesca; Marseglia, GIAN LUIGI; Miraglia del Giudice, Michele; Bodini, Alessandro; Martelli, Alberto; Baraldi, Eugenio; Mazzina, Oscar; Tagliabue, Claudia; Licari, Amelia; Ierardi, Valentina; Lelii, Mara; Principi, Nicol

Curr Biol

Efference copies are neural replicas of motor outputs used to anticipate the sensory consequences of a self-generated motor action or to coordinate neural networks involved in distinct motor behaviors. An established example of this motor-to-motor coupling is the efference copy of the propulsive motor command, which supplements classical visuo-vestibular reflexes to ensure gaze stabilization during amphibian larval locomotion. Such feedforward replica of spinal pattern-generating circuits produces a spino-extraocular motor coupled activity that evokes eye movements, spatiotemporally coordinated to tail undulation independently of any sensory signal. Exploiting the developmental stages of the frog, studies in metamorphing Xenopus demonstrated the persistence of this spino-extraocular motor command in adults and its developmental adaptation to tetrapodal locomotion. Here, we demonstrate for the first time the existence of a comparable locomotor-to-ocular motor coupling in the mouse. In neonates, ex vivo nerve recordings of brainstem-spinal cord preparations reveal a spino-extraocular motor coupled activity similar to the one described in Xenopus. In adult mice, trans-synaptic rabies virus injections in lateral rectus eye muscle label cervical spinal cord neurons closely connected to abducens motor neurons. Finally, treadmill-elicited locomotion in decerebrated preparations evokes rhythmic eye movements in synchrony with the limb gait pattern. Overall, our data are evidence for the conservation of locomotor-induced eye movements in vertebrate lineages. Thus, in mammals as in amphibians, CPG-efference copy feedforward signals might interact with sensory feedback to ensure efficient gaze control during locomotion.Corrélats neurophysiologiques de l'évolution et du développement des stratégies de stabilisation du regard pendant la locomotion chez les vertébrésUniversité de Pari