Measuring the effects of trade liberalization: multilevel analysis tool for agriculture

Bien que la globalisation et la libéralisation du commerce international soient maintenant largement acceptées dans le monde, la plupart des pays en voie de développement et de nombreuses économies de transition n'ont pas encore créé de systèmes de libres marchés. La représentation du monde économique réel avec la diversité des conditions économiques limite la spécialisation, l'investissement et l'adoption de nouvelles technologies. Les progrès en modélisation permettent maintenant la représentation de décisions économiques complexes. Dans cet ouvrage, un modèle pour le secteur agricole dans les bas-fonds de Java est présenté. Afin de représenter de façon pragmatique la complexité des décisions et les imperfections du marché, les occasions et les contraintes sont listées, les prix et les risques sont évalués. La description de l'agriculture vivrière en Indonésie a conduit à l'élaboration d'un modèle économique MATA développé pour estimer les impacts de diverses politiques. L'intérêt de ce projet est de fournir un outil de décision politique. La lecture du manuel MATA permettra d'étendre le modèle à d'autres zone

: Maurocalcine transduction into cells

International audienceMaurocalcine (MCa) is a 33-amino-acid residue peptide toxin isolated from the scorpion Scorpio maurus palmatus. External application of MCa to cultured myotubes is known to produce Ca2+ release from intracellular stores. MCa binds directly to the skeletal muscle isoform of the ryanodine receptor, an intracellular channel target of the endoplasmic reticulum, and induces long lasting channel openings in a mode of smaller conductance. Here we investigated the way MCa proceeds to cross biological membranes to reach its target. A biotinylated derivative of MCa was produced (MCa(b)) and complexed with a fluorescent indicator (streptavidine-cyanine 3) to follow the cell penetration of the toxin. The toxin complex efficiently penetrated into various cell types without requiring metabolic energy (low temperature) or implicating an endocytosis mechanism. MCa appeared to share the same features as the so-called cell-penetrating peptides. Our results provide evidence that MCa has the ability to act as a molecular carrier and to cross cell membranes in a rapid manner (1-2 min), making this toxin the first demonstrated example of a scorpion toxin that translocates into cells

Exon skipping as a therapeutic strategy applied to an RYR1 mutation with pseudo-exon inclusion causing a severe core myopathy.

International audienceCentral core disease is a myopathy often arising from mutations in the type 1 ryanodine receptor (RYR1) gene, encoding the sarcoplasmic reticulum calcium release channel RyR1. No treatment is currently available for this disease. We studied the pathological situation of a severely affected child with two recessive mutations, which resulted in a massive reduction in the amount of RyR1. The paternal mutation induced the inclusion of a new in-frame pseudo-exon in RyR1 mRNA that resulted in the insertion of additional amino acids leading to the instability of the protein. We hypothesized that skipping this additional exon would be sufficient to restore RyR1 expression and to normalize calcium releases. We therefore developed U7-AON lentiviral vectors to force exon skipping on affected primary muscle cells. The efficiency of the exon skipping was evaluated at the mRNA level, at the protein level, and at the functional level using calcium imaging. In these affected cells, we observed a decreased inclusion of the pseudo-exon, an increased RyR1 protein expression, and a restoration of calcium releases of normal amplitude either upon direct RyR1 stimulation or in response to membrane depolarization. This study is the first demonstration of the potential of exon-skipping strategy for the therapy of central core disease, from the molecular to the functional level

Addressing the problem of plastic waste: Development of an enzymatic process for PET recycling

Every day, media and NGOs describe the society\u27s disaffection for plastics accused of polluting the planet. All major brand-owners made commitments to solve this problem (e.g. Coca-Cola, Nestlé, Danone, PepsiCo, Suntory, Unilever, L’Oréal, Nike) and announced a future with less plastic waste by 2025. Nevertheless, only 6 years before the announced term, no effective solution is yet available to meet these goals. Indeed, existing technologies like thermo-mechanical recycling leads to loss in mechanical properties of the polymer and even if several chemical recycling processes are under development, they suffer from the disadvantages of using organic solvents, high reaction temperatures and the need of an intensive waste sorting. Consequently, enzymatic recycling appears as a pertinent solution notably because the enzyme selectivity avoids a drastic sorting of waste and enables the recycling of complex plastics (multi-layers construction in some bottles of sparkling water for instance), it is an eco-friendly reaction in water and because of savings in energy consumption due to a low temperature of reaction. Using a computer-aided engineering strategy, we drastically improved the depolymerizing performance of the best identified enzyme candidate. Utilizing site-directed mutagenesis targeted at the active site, combined with three-dimensional fold stabilization, we engineered an enzyme variant, demonstrating an astounding increase in thermostability combined with a high activity. This enzyme is able to depolymerize 90% of PET waste (200g/kg) into monomers, terephthalic acid and ethylene glycol, in less than 10 hours. The downstream processing was developed and optimized leading to the demonstration that this enzymatic technology could enable the use of an industrial plastic waste to produce again PET monomers and ultimately a bottle from this recycled PET. We hope to demonstrate the strong potential of the enzymatic technology jointly developed by CARBIOS and LISBP to provide a breakthrough solution to help solve society’s growing plastic waste problem

FIREBall-2: advancing TRL while doing proof-of-concept astrophysics on a suborbital platform

Here we discuss advances in UV technology over the last decade, with an emphasis on photon counting, low noise, high efficiency detectors in sub-orbital programs. We focus on the use of innovative UV detectors in a NASA astrophysics balloon telescope, FIREBall-2, which successfully flew in the Fall of 2018. The FIREBall-2 telescope is designed to make observations of distant galaxies to understand more about how they evolve by looking for diffuse hydrogen in the galactic halo. The payload utilizes a 1.0-meter class telescope with an ultraviolet multi-object spectrograph and is a joint collaboration between Caltech, JPL, LAM, CNES, Columbia, the University of Arizona, and NASA. The improved detector technology that was tested on FIREBall-2 can be applied to any UV mission. We discuss the results of the flight and detector performance. We will also discuss the utility of sub-orbital platforms (both balloon payloads and rockets) for testing new technologies and proof-of-concept scientific ideasComment: Submitted to the Proceedings of SPIE, Defense + Commercial Sensing (SI19

Recessive RYR1 mutations cause unusual congenital myopathy with prominent nuclear internalization and large areas of myofibrillar disorganization.

International audienceAIMS: To report the clinical, pathological and genetic findings in a group of patients with a previously not described phenotype of congenital myopathy due to recessive mutations in the gene encoding the type 1 muscle ryanodine receptor channel (RYR1). METHODS: Seven unrelated patients shared a predominant axial and proximal weakness of varying severity, with onset during the neonatal period, associated with bilateral ptosis and ophthalmoparesis, and unusual muscle biopsy features at light and electron microscopic levels. RESULTS: Muscle biopsy histochemistry revealed a peculiar morphological pattern characterized by numerous internalized myonuclei in up to 51% of fibres and large areas of myofibrillar disorganization with undefined borders. Ultrastructurally, such areas frequently occupied the whole myofibre cross section and extended to a moderate number of sarcomeres in length. Molecular genetic investigations identified recessive mutations in the ryanodine receptor (RYR1) gene in six compound heterozygous patients and one homozygous patient. Nine mutations are novel and four have already been reported either as pathogenic recessive mutations or as changes affecting a residue associated with dominant malignant hyperthermia susceptibility. Only two mutations were located in the C-terminal transmembrane domain whereas the others were distributed throughout the cytoplasmic region of RyR1. CONCLUSION: Our data enlarge the spectrum of RYR1 mutations and highlight their clinical and morphological heterogeneity. A congenital myopathy featuring ptosis and external ophthalmoplegia, concomitant with the novel histopathological phenotype showing fibres with large, poorly delimited areas of myofibrillar disorganization and internal nuclei, is highly suggestive of an RYR1-related congenital myopathy

Cardiomyocyte overexpression of neuronal nitric oxide synthase delays transition toward heart failure in response to pressure overload by preserving calcium cycling.

International audienceBACKGROUND: Defects in cardiomyocyte Ca(2+) cycling are a signature feature of heart failure (HF) that occurs in response to sustained hemodynamic overload, and they largely account for contractile dysfunction. Neuronal nitric oxide synthase (NOS1) influences myocyte excitation-contraction coupling through modulation of Ca(2+) cycling, but the potential relevance of this in HF is unknown. METHODS AND RESULTS: We generated a transgenic mouse with conditional, cardiomyocyte-specific NOS1 overexpression (double-transgenic [DT]) and studied cardiac remodeling, myocardial Ca(2+) handling, and contractility in DT and control mice subjected to transverse aortic constriction (TAC). After TAC, control mice developed eccentric hypertrophy with evolution toward HF as revealed by a significantly reduced fractional shortening. In contrast, DT mice developed a greater increase in wall thickness (P<0.0001 versus control+TAC) and less left ventricular dilatation than control+TAC mice (P<0.0001 for both end-systolic and end-diastolic dimensions). Thus, DT mice displayed concentric hypertrophy with fully preserved fractional shortening (43.7+/-0.6% versus 30.3+/-2.6% in control+TAC mice, P<0.05). Isolated cardiomyocytes from DT+TAC mice had greater shortening, intracellular Ca(2+) transients, and sarcoplasmic reticulum Ca(2+) load (P<0.05 versus control+TAC for all parameters). These effects could be explained, at least in part, through modulation of phospholamban phosphorylation status. CONCLUSIONS: Cardiomyocyte NOS1 may be a useful target against cardiac deterioration during chronic pressure-overload-induced HF through modulation of calcium cycling

Pet recycling: From enzyme and process optimization to an industrial plant

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Genome analysis of the necrotrophic fungal pathogens Sclerotinia sclerotiorum and Botrytis cinerea

Sclerotinia sclerotiorum and Botrytis cinerea are closely related necrotrophic plant pathogenic fungi notable for their wide host ranges and environmental persistence. These attributes have made these species models for understanding the complexity of necrotrophic, broad host-range pathogenicity. Despite their similarities, the two species differ in mating behaviour and the ability to produce asexual spores. We have sequenced the genomes of one strain of S. sclerotiorum and two strains of B. cinerea. The comparative analysis of these genomes relative to one another and to other sequenced fungal genomes is provided here. Their 38–39 Mb genomes include 11,860–14,270 predicted genes, which share 83% amino acid identity on average between the two species. We have mapped the S. sclerotiorum assembly to 16 chromosomes and found large-scale co-linearity with the B. cinerea genomes. Seven percent of the S. sclerotiorum genome comprises transposable elements compared t

Highly-multiplexed SNP genotyping for genetic mapping and germplasm diversity studies in pea

Background: Single Nucleotide Polymorphisms (SNPs) can be used as genetic markers for applications such as genetic diversity studies or genetic mapping. New technologies now allow genotyping hundreds to thousands of SNPs in a single reaction. In order to evaluate the potential of these technologies in pea, we selected a custom 384-SNP set using SNPs discovered in Pisum through the resequencing of gene fragments in different genotypes and by compiling genomic sequence data present in databases. We then designed an Illumina GoldenGate assay to genotype both a Pisum germplasm collection and a genetic mapping population with the SNP set. Results: We obtained clear allelic data for more than 92% of the SNPs (356 out of 384). Interestingly, the technique was successful for all the genotypes present in the germplasm collection, including those from species or subspecies different from the P. sativum ssp sativum used to generate sequences. By genotyping the mapping population with the SNP set, we obtained a genetic map and map positions for 37 new gene markers. Conclusion: Our results show that the Illumina GoldenGate assay can be used successfully for high-throughput SNP genotyping of diverse germplasm in pea. This genotyping approach will simplify genotyping procedures for association mapping or diversity studies purposes and open new perspectives in legume genomics