Dominant ACO2 mutations are a frequent cause of isolated optic atrophy.

Biallelic mutations in ACO2, encoding the mitochondrial aconitase 2, have been identified in individuals with neurodegenerative syndromes, including infantile cerebellar retinal degeneration and recessive optic neuropathies (locus OPA9). By screening European cohorts of individuals with genetically unsolved inherited optic neuropathies, we identified 61 cases harbouring variants in ACO2, among whom 50 carried dominant mutations, emphasizing for the first time the important contribution of ACO2 monoallelic pathogenic variants to dominant optic atrophy. Analysis of the ophthalmological and clinical data revealed that recessive cases are affected more severely than dominant cases, while not significantly earlier. In addition, 27% of the recessive cases and 11% of the dominant cases manifested with extraocular features in addition to optic atrophy. In silico analyses of ACO2 variants predicted their deleterious impacts on ACO2 biophysical properties. Skin derived fibroblasts from patients harbouring dominant and recessive ACO2 mutations revealed a reduction of ACO2 abundance and enzymatic activity, and the impairment of the mitochondrial respiration using citrate and pyruvate as substrates, while the addition of other Krebs cycle intermediates restored a normal respiration, suggesting a possible short-cut adaptation of the tricarboxylic citric acid cycle. Analysis of the mitochondrial genome abundance disclosed a significant reduction of the mitochondrial DNA amount in all ACO2 fibroblasts. Overall, our data position ACO2 as the third most frequently mutated gene in autosomal inherited optic neuropathies, after OPA1 and WFS1, and emphasize the crucial involvement of the first steps of the Krebs cycle in the maintenance and survival of retinal ganglion cells

Polyethylene composites made from below-ground miscanthus biomass

International audienceMiscanthus is a perennial grass which may be interesting for the composite industrial sector. When the cycle of the crop comes to the end, the biomass below ground need to be valorized. One never-studied topic is to evaluate its potential valorization as composites. Below-ground (rhizomes plus roots) biomass of Miscanthus × giganteus cultivated on three different blocks with three different nitrogen fertilization levels were collected, ground, sieved and used as fillers in a polyethylene matrix. Miscanthus rhizome plus roots fragments have a very low axial ratio around two, in contrast with stem fragments which are three to four times more elongated. The mechanical properties of composites filed with rhizome plus roots fragments are much below the ones of the composites filled with stem fragments. The tensile strength is about half the values of stem composites (7.4 MPa for rhizomes compared with 13 MPa for stems) and there is a very large drop of the Young’s modulus, down to 260 MPa compared with 900–1000 MPa for stems. Only impact strength has good values (6–7 kJ/m2). The very low aspect ratio of the rhizome fragments combined with the fact that there are twice more cellulose in stems than in rhizomes with a non cellulosic polysaccharides-cellulose ratio being twice larger for rhizomes (about 1 for rhizomes and 0.45 for stems) are both acting in the same direction of lowering the mechanical properties of rhizome fragment-based polymer composites. These low mechanical properties are restricting the use of such composites to applications were the low cost is the main factor of choice

MEG evidence for dynamic amygdala modulations by gaze and facial emotions.

Amygdala is a key brain region for face perception. While the role of amygdala in the perception of facial emotion and gaze has been extensively highlighted with fMRI, the unfolding in time of amydgala responses to emotional versus neutral faces with different gaze directions is scarcely known.Here we addressed this question in healthy subjects using MEG combined with an original source imaging method based on individual amygdala volume segmentation and the localization of sources in the amygdala volume. We found an early peak of amygdala activity that was enhanced for fearful relative to neutral faces between 130 and 170 ms. The effect of emotion was again significant in a later time range (310-350 ms). Moreover, the amygdala response was greater for direct relative averted gaze between 190 and 350 ms, and this effect was selective of fearful faces in the right amygdala.Altogether, our results show that the amygdala is involved in the processing and integration of emotion and gaze cues from faces in different time ranges, thus underlining its role in multiple stages of face perception

Cortical sources of activity.

<p>A) Mean cortical current maps between 130 and 170 ms. The colour-coded activity of cortical dipole sources (in z-score units), averaged across all subjects and conditions, is superimposed on the ventral, back, right and left lateral views of an inflated template brain. Only sources with amplitude above 60% of the scale maximum activity are displayed. B) Time course of cortical source activity in fusiform regions under each experimental condition. The cortical source activity averaged across all subjects over the right and left fusiform clusters respectively (displayed in red on a ventral view of the brain, in a small inset) is presented. C) Time course of cortical source activity in lateral occipital regions under each experimental condition. The cortical source activity averaged across all subjects over the right and left lateral occipital clusters respectively (displayed in red on lateral views of the template brain, in small insets) is presented. The time windows where the mean amplitude of cortical source activity was measured are shaded in grey.</p

Event-related magnetic fields (ERFs) in response to faces.

<p>On the top: Maps (top-view of the head) of the ERFs at 80, 106 and 144 ms, averaged across all subjects and conditions. Below: Superimposed time courses of the ERFs over the 151 sensors, averaged across all subjects and conditions.</p

Illustration of the anatomical segmentation of the amygdala and the hippocampus from the individual T1 MRI scan of a typical subject.

<p>On the left: Amygdala (in green) and hippocampus (in red) segmentation masks obtained with the method of Chupin and coll. (2007) are visualized on a horizontal view of the participant’s anatomical MRI. On the right: Top view of the tessellated surfaces of the amygdala (in green) and the hippocampus (in red) merged with the tessellated cortical surface (obtained with BrainVisa) from the same individual’s MRI scan.</p

Mean number of sources (±SEM) distributed in the amygdala volume and over the cortical surface across subjects.

<p>Mean number of sources (±SEM) distributed in the amygdala volume and over the cortical surface across subjects.</p

Amygdala responses to the faces.

<p>A) Time course of the right and left amygdala responses to the fearful (in red) and neutral (in black) faces with direct (plain line) and averted gaze (dashed line). The amygdala activity averaged across the 15 subjects is presented. The time windows where the mean amplitude of amygdala activity was measured are shaded in grey. B) Plots of the effect of emotion and gaze on amygdala activity between 130 and 170 ms and between 190 and 350 ms. On the left: A main effect of the emotion conveyed by the face was observed between 130 and 170 ms. On the middle and right: A main effect of gaze direction qualified by an interaction with emotion and hemisphere was observed between 190 and 350 ms. This reflected a significantly greater response to fearful faces with direct gaze than to fearful faces with averted gaze and to neutral faces with direct gaze in the right amygdala. On every plot, the error bars represent the standard errors of the means across subjects (SEM). C) Correlation between the amygdala activity and the participants’ anxiety score (STAI). This correlation was observed in both time ranges of amygdala activity measurement (130–170 ms and 190–350 ms).</p

Metabolomics reveals highly regional specificity of cerebral sexual dimorphism in mice

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