Bone Marrow Transplant

Mucopolysaccharidosis type I-H (MPS I-H) is a rare lysosomal storage disorder caused by α-L-Iduronidase deficiency. Early haematopoietic stem cell transplantation (HSCT) is the sole available therapeutic option to preserve neurocognitive functions. We report long-term follow-up (median 9 years, interquartile range 8-16.5) for 51 MPS I-H patients who underwent HSCT between 1986 and 2018 in France. 4 patients died from complications of HSCT and one from disease progression. Complete chimerism and normal α-L-Iduronidase activity were obtained in 84% and 71% of patients respectively. No difference of outcomes was observed between bone marrow and cord blood stem cell sources. All patients acquired independent walking and 91% and 78% acquired intelligible language or reading and writing. Intelligence Quotient evaluation (n = 23) showed that 69% had IQ ≥ 70 at last follow-up. 58% of patients had normal or remedial schooling and 62% of the 13 adults had good socio-professional insertion. Skeletal dysplasia as well as vision and hearing impairments progressed despite HSCT, with significant disability. These results provide a long-term assessment of HSCT efficacy in MPS I-H and could be useful in the evaluation of novel promising treatments such as gene therapy

Characterisation of the Viral Community Associated with the Alfalfa Weevil (Hypera postica) and Its Host Plant, Alfalfa (Medicago sativa)

International audienceAdvances in viral metagenomics have paved the way of virus discovery by making the exploration of viruses in any ecosystem possible. Applied to agroecosystems, such an approach opens new possibilities to explore how viruses circulate between insects and plants, which may help to optimise their management. It could also lead to identifying novel entomopathogenic viral resources potentially suitable for biocontrol strategies. We sampled the larvae of a natural population of alfalfa weevils (Hypera postica), a major herbivorous pest feeding on legumes, and its host plant alfalfa (Medicago sativa). Insect and plant samples were collected from a crop field and an adjacent meadow. We characterised the diversity and abundance of viruses associated with weevils and alfalfa, and described nine putative new virus species, including four associated with alfalfa and five with weevils. In addition, we found that trophic accumulation may result in a higher diversity of plant viruses in phytophagous pests compared to host plants

Novel Intronic Mutation in VMA21 Causing Severe Phenotype of X-Linked Myopathy with Excessive Autophagy—Case Report

X-linked Myopathy with Excessive Autophagy (XMEA) is a rare autophagic vacuolar myopathy caused by mutations in the Vacuolar ATPase assembly factor VMA21 gene; onset usually occurs during childhood and rarely occurs during adulthood. We described a 22-year-old patient with XMEA, whose onset was declared at 11 through gait disorder. He had severe four-limb proximal weakness and amyotrophy, and his proximal muscle MRC score was between 2 and 3/5 in four limbs; creatine kinase levels were elevated (1385 IU/L), and electroneuromyography and muscle MRI were suggestive of myopathy. Muscle biopsy showed abnormalities typical of autophagic vacuolar myopathy. We detected a hemizygous, unreported, intronic, single-nucleotide substitution c.164-20T>A (NM_001017980.4) in intron 2 of the VMA21 gene. Fibroblasts derived from this patient displayed a reduced level of VMA21 transcripts (at 40% of normal) and protein, suggesting a pathogenicity related to an alteration of the splicing efficiency associated with an intron retention. This patient with XMEA displayed a severe phenotype (rapid weakness of upper and lower limbs) due to a new intronic variant of VMA21, related to an alteration in the splicing efficiency associated with intron retention, suggesting that phenotype severity is closely related to the residual expression of the VMA21 protein

Methylprednisolone-induced immune thrombocytopenia

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Methylprednisolone‐induced immune thrombocytopenia

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Gene Editing Corrects In Vitro a G > A GLB1 Transition from a GM1 Gangliosidosis Patient

International audienceGanglioside-monosialic acid (GM1) gangliosidosis, a rare autosomal recessive disorder, is frequently caused by deleterious single nucleotide variants (SNVs) in GLB1 gene. These variants result in reduced β-galactosidase (β-gal) activity, leading to neurodegeneration associated with premature death. Currently, no effective therapy for GM1 gangliosidosis is available. Three ongoing clinical trials aim to deliver a functional copy of the GLB1 gene to stop disease progression. In this study, we show that 41% of GLB1 pathogenic SNVs can be replaced by adenine base editors (ABEs). Our results demonstrate that ABE efficiently corrects the pathogenic allele in patient-derived fibroblasts, restoring therapeutic levels of β-gal activity. Off-target DNA analysis did not detect off-target editing activity in treated patient’s cells, except a bystander edit without consequences on β-gal activity based on 3D structure bioinformatics predictions. Altogether, our results suggest that gene editing might be an alternative strategy to cure GM1 gangliosidosis

L'État et l'enseignement privé

Il y a cinquante ans était votée, dans des circonstances difficiles, la loi dite « Debré » qui régit encore les rapports entre les établissements d'enseignement privés et l'État. Un bilan de l'application de cette loi fondatrice à tous égards s'imposait, réalisé par des chercheurs en sciences de l'éducation, droit, histoire et sociologie, mais également grâce à des témoins et des acteurs ayant eu ou ayant des responsabilités au plus haut niveau dans le déroulement des évènements. Quatre moments ordonnent le contenu de cet ouvrage : un bilan historique confronté à la mémoire de grands témoins des évènements depuis le vote de la loi Debré jusqu'à l'échec de sa transformation par la loi Savary ; un bilan centré sur la question très sensible du statut des maîtres contractuels : caractère propre, rapport aux congrégations, gestion et formation initiale et continue des enseignants ; un bilan sur l'espace occupé par les établissements privés sur le territoire français : sociologie des élèves, choix des parents, rapports aux questions économiques et développement d'un secteur marchand aux frontières de l'école sous le regard croisé des acteurs que sont les parents d'élèves ; et un bilan enfin sur l'identité même des établissements privés : établissements juifs, musulmans, nouvelles écoles catholiques, rapport au marché et au service public. Cinquante après la loi Debré où en sommes-nous ? Cet ouvrage tente d'y répondre et de dresser un bilan aussi nuancé et rigoureux que possible de l'application d'une loi qui a fait débat et continue à le faire parce qu'elle se prête à de multiples interprétations. La loi Debré participe-t-elle de cette « composition française » dont parle Mona Ozouf ou au contraire a-t-elle dressé une barrière entre des cultures éducatives différentes ? Rapprochement et séparation constituent bien le paradoxe actuel des établissements privés par rapport aux établissements publics

The <i>Bal des Ardents</i> (1393), Thomas of Woodstock (1397) and Richard II (1400): Three Medieval Conspiracy Rumours and the Scots’ Mine Play (1608).

Assassination vehicles in Elizabethan and Jacobean tragedies sometimes involve meta-theatrical court festival massacres: court performances embedded within full-length drama, resulting in violent death or trauma to characters in the play. During his career as a playwright (c. 1600–08), John Marston pioneered the masquerade-within as a popular sub-category of court festival massacre. Were such underhand festival appropriations wholly inspired by stage precedents? Or did they also occur in real life? Whether its deaths were accidental or resulted from a botched assassination plot, the 1393 Bal des Ardents was hugely culturally and politically influential. Its continuing cultural afterlives bear witness to the geographical, chronological and social shockwaves of a medieval event whose impact illuminates the persistent collective trauma generated by extreme modern assassinations. My researches identify the conspiracy rumours encouraged in the wake of the 1393 Paris disaster and two English conspiracies of 1397 and 1400 linked to court festivals, as key to a fresh approach to the meta-theatrical court festival massacre, and to interpretation of two plays traditionally discussed together, which refer to these English conspiracies, Shakespeare’s Richard II and the anonymous Thomas of Woodstock. My analysis supports a post-Elizabethan dating of Woodstock, and encourages the hypothesis that it could be the so-called Scots’ Mine Play of 1608, the lost Jacobean play thought by some to have ended Marston’s career as a playwright