Laboratoire de Neurobiologie Cellulaire et Moléculaire

A recent information processing model of two-choice RT situations (Servant et al., 2015), suggests that conditions which reduce the duration of peripheral motor processes, should also reduce the efficiency of the action monitoring system, because letting no time enough for correction of partial errors (i.e. subthreshold transient muscle activity of the agonists of the incorrect response preceding the correct response). A physiological situation, namely sustained physical exercise, has repeatedly been reported to reduce the duration of response execution. Therefore, in order to test the prediction of the model, we compared action monitoring efficiency between a sustained exercise (59.42% of MAP) and a control (15 W) condition in the same subjects while they were performing a Simon task. Electromyographic (EMG) recordings of muscles implicated in the response allowed to measure premotor time (time interval between the stimulus and the onset of the EMG burst) and motor time (MT, time interval between the onset of the EMG burst and the mechanical response, which gives access to response execution processes). Electromyogram further permitted to unmask partial errors. Correction ratio was calculated by dividing the number of partial errors by the number of incorrect activations (partial errors + errors). As expected, exercise decreased MT. In addition, exercise reduced the correction ratio. Furthermore, there was a positive inter-subject correlation between these two dependent variables. In line with Servant et al.'s model (2015), we propose that the drop in the efficiency of cognitive control was due to insufficient MT available for action monitoring to operate when incorrect activations were produced.

The quantitative and systematic analysis of embryonic cell dynamics from in vivo 3D+time image data sets is a major challenge at the forefront of developmental biology. Despite recent breakthroughs in the microscopy imaging of living systems, producing an accurate cell lineage tree for any developing organism remains a difficult task. We present here the BioEmergences workflow integrating all reconstruction steps from image acquisition and processing to the interactive visualization of reconstructed data. Original mathematical methods and algorithms underlie image filtering, nucleus centre detection, nucleus and membrane segmentation, and cell tracking. They are demonstrated on zebrafish, ascidian and sea urchin embryos with stained nuclei and membranes. Subsequent validation and annotations are carried out using Mov-IT, a custom-made graphical interface. Compared with eight other software tools, our workflow achieved the best lineage score. Delivered in standalone or web service mode, BioEmergences and Mov-IT offer a unique set of tools for in silico experimental embryology.

Despite legislative advances in terms of workplace equality for sexual and gender minorities (SGM), available data ascertains the persistence of workplace discrimination of lesbian, gay, bisexual, and especially of transgender/transsexual employees. This article, based on an extensive literature review, explores the relationship between different types of workplace discrimination experiences and their impacts on the mental health of SGM and of different sub-populations: men who have sex with men, non-heterosexual women, lesbian and gay parents, and trans people. Furthermore, the article explores certain individual and systemic protection and risk factors that have an impact on this relationship, such as coming-out at work and organisational support. Finally, the existing literature on workplace discrimination and mental health of sexual and gender minorities highlights the importance, in the current legal and social context, of intersectional approaches and of research on homo- and trans-negative microaggressions. The article ends with a discussion on the implications for practice, research, and workplace settings, as well as with several recommendations for these settings.

Protein-coding mutations in the transcription factor-encoding gene ARX cause various forms of intellectual disability (ID) and epilepsy. In contrast, variations in surrounding non-coding sequences are correlated with milder forms of non-syndromic ID and autism and had suggested the importance of ARX gene regulation in the etiology of these disorders. We compile data on several novel and some already identified patients with or without ID that carry duplications of ARX genomic region and consider likely genetic mechanisms underlying the neurodevelopmental defects. We establish the long-range regulatory domain of ARX and identify its brain region-specific autoregulation. We conclude that neurodevelopmental disturbances in the patients may not simply arise from increased dosage due to ARX duplication. This is further exemplified by a small duplication involving a non-functional ARX copy, but with duplicated enhancers. ARX enhancers are located within a 504-kb region and regulate expression specifically in the forebrain in developing and adult zebrafish. Transgenic enhancer-reporter lines were used as in vivo tools to delineate a brain region-specific negative and positive autoregulation of ARX. We find autorepression of ARX in the telencephalon and autoactivation in the ventral thalamus. Fluorescently labeled brain regions in the transgenic lines facilitated the identification of neuronal outgrowth and pathfinding disturbances in the ventral thalamus and telencephalon that occur when arxa dosage is diminished. In summary, we have established a model for how breakpoints in long-range gene regulation alter the expression levels of a target gene brain region-specifically, and how this can cause subtle neuronal phenotypes relating to the etiology of associated neuropsychiatric disease.