Mouse Studies to Shape Clinical Trials for Mitochondrial Diseases: High Fat Diet in Harlequin Mice

BACKGROUND: Therapeutic options in human mitochondrial oxidative phosphorylation (OXPHOS) diseases have been poorly evaluated mostly because of the scarcity of cohorts and the inter-individual variability of disease progression. Thus, while a high fat diet (HFD) is often recommended, data regarding efficacy are limited. Our objectives were 1) to determine our ability to evaluate therapeutic options in the Harlequin OXPHOS complex I (CI)-deficient mice, in the context of a mitochondrial disease with human hallmarks and 2) to assess the effects of a HFD. METHODS AND FINDINGS: Before launching long and expensive animal studies, we showed that palmitate afforded long-term death-protection in 3 CI-mutant human fibroblasts cell lines. We next demonstrated that using the Harlequin mouse, it was possible to draw solid conclusions on the efficacy of a 5-month-HFD on neurodegenerative symptoms. Moreover, we could identify a group of highly responsive animals, echoing the high variability of the disease progression in Harlequin mice. CONCLUSIONS: These results suggest that a reduced number of patients with identical genetic disease should be sufficient to reach firm conclusions as far as the potential existence of responders and non responders is recognized. They also positively prefigure HFD-trials in OXPHOS-deficient patients

Methane production from anaerobic co-digestion of orange peel waste and organic fraction of municipal solid waste in batch and semi-continuous reactors

A large amount of orange peel waste (OPW) is yearly generated due to the high production of oranges all over the world. A high percentage of this waste is dumped every year without any proper treatment, thus causing environmental issues as a consequence of dispersion of biological degradation by-products (i.e. biogas and leachate) into the environment. An effective, suitable and environmentally friendly treatment for OPW is therefore required. Biogas production under controlled conditions by an anaerobic digestion (AD) process is highly recommendable and it has been demonstrated to be potentially high efficient when OPW is used as substrate. However, the high content of essential oils, mainly composed of limonene, a well-known antioxidant, can cause the inhibition of the biological activity. A low limonene concentration inside the anaerobic digester can be effective to avoid this inhibition. Therefore, anaerobic co-digestion of OPW with organic fraction of municipal solid waste (OFMSW) was carried out in order to reduce limonene concentration, by dilution, in the organic mixture. Three different mass ratios of the two substrates (i.e. 1:3, 2:2, 3:1) were considered (each of them with different limonene concentrations) and used in two separate experiments: batch and semi continuous. The content of limonene inside the digester is directly related to the organic loading rate (OLR). The maximum OLR that resulted in stable anaerobic co-digestion process performance was 2 gVS(L−1·day−1) corresponding to 26.7 mgLimonene(Ldigester−1·day−1) of limonene dosage. The highest methane production obtained from such an OLR was around 0.70 ± 0.05 LCH4(Ldigester−1·day−1)

Progress in fabrication of long transparent YAG:Ce and YAG:Ce,Mg single crystalline fibers for HEP applications

International audienceA significant enhancement in the light attenuation length in 22 cm long YAG:Ce and YAG:Ce,Mg fibers grown by the micro-pulling-down method has been reported. This progress has been achieved by the introduction of Al excess into the melt, optimization of thermal conditions of crystallization and post growth annealing. Attenuation length clearly correlates with surface roughness of the fibers. Al excess addition over the stoichiometric composition enhances the fiber surface smoothness. An increase in axial thermal gradient and melt pressure in the crucible capillary die improves the crystallization process stability. Mg codoping provides a Ce3+ scintillation decay time decrease down to 80 ns

La paradoxe du Sahel est il toujours paradoxal ?

International audienc

Seed orientation and pulling rate effects on bubbles and strain distribution on a sapphire crystal grown by the micro-pulling down method

International audienceUndoped sapphire rod crystals (ϕ = 3 mm, length ≈ 170 mm) along different crystallographic orientations (a [11[2 with combining macron]0], m [10[1 with combining macron]0], c [0001] and c [0001] shifted 30° off axis) were successfully grown by the micro-pulling down (μ-PD) method. The bubble defect distribution was investigated as a function of the thermal gradient and pulling rates. It is observed that sapphire rods grown at a low pulling rate (v < 200 μm min−1) were bubble-free. A homogeneous temperature distribution around the capillary die will limit the bubble propagation. Pulling sapphire rods along the c-axis is a good way to minimize the bubble propagation. The effects of growth parameters on bubble and strain distribution in sapphire rods grown from μ-PD rods were discussed