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To evaluate sensitivity to change and discriminant validity of the 20-item Motor Function Measure (MFM-20) in 2-7-year-old patients with spinal muscular atrophy types 1 (SMA1) or 2 (SMA2) treated with nusinersen.Children aged 2 to 7 years old with SMA1 or SMA2 treated with nusinersen were assessed at least three times using the MFM-20 over an average follow-up time of 17 months. Evolution of 4-month-standardized MFM-20 scores was calculated for each MFM-20 domain (D1 standing and transfers, D2 axial and proximal, D3 distal) and for the total score (TS).Included in the study were 22 SMA1 subjects and 19 SMA2 subjects. Baseline MFM scores were significantly lower in patients with SMA1 than SMA2 (TS 29.5% vs. 48.3%, D1 4.5% vs. 10.6%, D2 43.6% vs. 72.6%, D3 51.2% vs. 75.0%). When considering the mean change during nusinersen treatment, standardized over a 4-month period, TS was improved for both SMA1 (+ 4.1%, SRM 1.5) and SMA2 (+ 2.8%, SRM 0.89) patients. For SMA1 patients, considerable changes were observed in D2 (+ 6.2%, SRM 0.89) and D3 (+ 6.0%, SRM 0.72), whereas the change in D1 was small (+ 0.5%, SRM 0.44). In SMA2 2 subjects, D3 was improved to a larger extent (+ 4.2%, SRM 0.53) than D1 (+ 1.8% SRM 0.63) or D2 (+ 3.2%, SRM 0.69).Our results validate use of MFM-20 to monitor function of young SMA1 and SMA2 subjects treated with nusinersen. Significant motor function improvements following treatment were observed in both SMA1 and SMA2 patients.

AgroSup Dijon is a French public Institution of Higher Education for agronomic sciences, food and the environment. It is the only French public institution accredited to issue graduate level (Master and Doctoral degrees) in Agricultural Machinery and Precision Farming with a team of academics specialised in agricultural equipment and innovative technologies dedicated to Precision Agriculture. Close ties to industry offer our graduates the opportunity to develop their professional skills. Our programs combine hands-on learning with relevant classroom work. However, times are changing for the agricultural machinery branch. International trade is an everyday fact, for most companies. Companies need to upgrade new skills on digital farming, AgTech and agroecology. A double revolution, digital and agroecology, is underway and so, a broad cross-section of new skills is required to train future leaders, managers, teachers, doctors and other professionals. OBJECTIVES. AN INDUSTRIAL CHAIR DEDICATED TO TRAINING To meet this new challenge and consolidate its leadership position, AgroSup Dijon must constantly renew its educational strategy by exploring innovative pedagogical practices while remaining close to industrial companies including recruitment and training. Thus, we have started to develop a new educational tool; an industrial chair called ‘Tech Agro Sup’ and dedicated to training; that is the aim of this presentation. Nevertheless, the success of AgroSup Dijon depends on the availability of private funds through the support of industrial partners. Action plan: let us work together to promote the most up-to-date training requirements. The 3 topics addressed by the chair are: 1. A showcase to highlight our higher educational map based on the development of precision agriculture combining agro-ecological transition with digital revolution. This allows companies to work with us to attract new graduates and researchers in agricultural engineering and related sectors, as well as to improve the skills of those working in the industry through ongoing professional development and the most upto- date technical training. 2. A partnership with agricultural equipment firms. These firms decide to support the project via a sponsorship. These firms have a key role to play in the success of this ambitious project to attract and train young people in emerging technology by knowledge sharing. 3. A sharing of our International networks. Our relationship with universities in Italy, Ireland and more recently Germany (Rhineland-Palatinate Land) means the corporate contributors (Fig. 1) can recruit young talent from other countries that they may export their product to. Working with industrial companies and foreign universities, the ambition is to become a European leader of training, exchanges and expertise in agricultural equipment and precision agriculture in 5 years. Various proposals have been explored and the most relevant is presented below (Fig. 1). 73 Figure 1: Launched in 2018, the Tech Agro Sup Chair encourages industrial partnership in the agricultural machinery branch and sharing knowledge between corporate contributors and international academic partners to train and recruit young talents Ongoing action: Postgraduate programme in international agricultural engineering. The Institute of Technology of Chalon-sur-Saône, Vesoul Agrocampus and Agrosup Dijon in France, the Institute of Technology of Tralee in Ireland as well as the University of Bologna in Italy will offer as an add-on to the current level 7 degree in international agricultural engineering. It will begin in September 2019 and the course is 1 year in total, with an initial intake of 15 students. The main objective is to equip students with highly specialized competences and solid transversal skills all embedded in an international dimension. The classes will be in English. Students will originate from a bachelor degree in Agriculture Equipment or a BSc in Agricultural Mechanization. They will have skills in agriculture, mechanical engineering, agriculture equipment science and techniques. Students will move across the three countries rotating each quarter in one of the Partner Institutions, including a 3 months internship experience. The 1st quarter will take place in Ireland (Module 1: design & Control), followed by Italy (Module 2: Performances & testing) and France (Precision farming &Agribotics). The final quarter will be work placement. At the end of the programme, students will get the necessary professional qualifications for playing important roles in the main industries operating in the sector. CONCLUSION To promote the agricultural machinery branch, its activities and its occupations, it is necessary to attract more young people in our higher education and to work in close collaboration with industrialists who require continually updating their skills and competencies. Thus, AgroSup Dijon developed the Tech Agro Sup Chair, based on sponsorship. Whether you are a manufacturer, a research institute or a university and if you are interesting to contribute to train future international leaders in innovative technologies for agricultural equipment, do not hesitate: JOIN US!

Congenital nephron number varies widely in the human population and individuals with low nephron number are at risk of developing hypertension and chronic kidney disease. The development of the kidney occurs via an orchestrated morphogenetic process where metanephric mesenchyme and ureteric bud reciprocally interact to induce nephron formation. The genetic networks that modulate the extent of this process and set the final nephron number are mostly unknown. Here, we identified a specific isoform of MITF (MITF-A), a bHLH-Zip transcription factor, as a novel regulator of the final nephron number. We showed that overexpression of MITF-A leads to a substantial increase of nephron number and bigger kidneys, whereas Mitfa deficiency results in reduced nephron number. Furthermore, we demonstrated that MITF-A triggers ureteric bud branching, a phenotype that is associated with increased ureteric bud cell proliferation. Molecular studies associated with an in silico analyses revealed that amongst the putative MITF-A targets, Ret was significantly modulated by MITF-A. Consistent with the key role of this network in kidney morphogenesis, Ret heterozygosis prevented the increase of nephron number in mice overexpressing MITF-A. Collectively, these results uncover a novel transcriptional network that controls branching morphogenesis during kidney development and identifies one of the first modifier genes of nephron endowment., Author summary The number of nephrons, the functional unit of kidney, varies widely among humans. Indeed, it has been shown that kidneys may contain from 0.3 to more than 2 million of nephrons. Nephrons are formed during development via a coordinated morphogenetic program in which the metanephric mesenchyme reciprocally and recursively interacts with the ureteric bud. The fine-tuning of this cross-talk determines the final number of nephrons. Strong evidence indicates that suboptimal nephron endowment is associated with an increased risk of hypertension and chronic kidney disease, a major healthcare burden. Indeed, chronic kidney disease is characterized by the progressive decline of renal function towards end stage renal disease, which occurs once a critical number of nephrons has been lost. Elucidating the molecular mechanisms that control nephron endowment is, therefore, a critical issue for public health. However, little is known about the factors that determine the final number of nephrons in the healthy population. Our data showed that nephron endowment is genetically predetermined and identified Mitfa, a bHLH transcription factor, as one of the first modifiers of nephron formation during kidney development. By generating an allelic series of transgenic mice expressing different levels of MITF-A, we discovered that MITF-A promotes final nephron endowment. In addition, we elucidated the molecular mechanisms by which MITF-A promotes nephron formation and identified RET as one of the critical effectors.

The molecular networks that control the progression of chronic kidney diseases (CKD) are poorly defined. We have recently shown that the susceptibility to development of renal lesions after nephron reduction is controlled by a locus on mouse chromosome 6 and requires epidermal growth factor receptor (EGFR) activation. Here, we identified microphthalmia-associated transcription factor A (MITF-A), a bHLH-Zip transcription factor, as a modifier of CKD progression. Sequence analysis revealed a strain-specific mutation in the 5′ UTR that decreases MITF-A protein synthesis in lesion-prone friend virus B NIH (FVB/N) mice. More importantly, we dissected the molecular pathway by which MITF-A modulates CKD progression. MITF-A interacts with histone deacetylases to repress the transcription of TGF-α, a ligand of EGFR, and antagonizes transactivation by its related partner, transcription factor E3 (TFE3). Consistent with the key role of this network in CKD, Tgfa gene inactivation protected FVB/N mice from renal deterioration after nephron reduction. These data are relevant to human CKD, as we found that the TFE3/MITF-A ratio was increased in patients with damaged kidneys. Our study uncovers a novel transcriptional network and unveils novel potential prognostic and therapeutic targets for preventing human CKD progression.

Signaling of all-trans retinoic acid (ATRA) through nuclear retinoid acid (RA) receptors regulates several biological functions in airway epithelial cells, eosinophils, and immune cells, yet its impact on different in vivo aspects of pulmonary allergic reaction remains elusive. We compared the effect of a treatment with liposomally encapsulated ATRA (Lipo-ATRA) in a mouse model of ovalbumin (OVA)-induced T helper (Th) 2-type responses and airway remodeling. Daily intraperitoneal injections of 10 mg/kg Lipo-ATRA, at the time of each of the 2 systemic sensitizing injections, increased OVA-induced Immunoglobulin E synthesis, bronchoalveolar lavage (BAL) eosinophilia, and accumulation of IL-5, transforming-growth factor b1, fibronectin, eotaxin/chemokine (C-C motif) ligand 11 (eotaxin/CCL11) and regulated upon activation, normal T expressed and secreted chemokine (C-C motif) ligand 5. In contrast, Lipo-ATRA, administered during each of the 4 intranasal OVA challenges, did not affect these variables. Regardless of the treatment regimen, Lipo-ATRA augmented mucin levels in BAL fluid and reduced lung total collagen content. In vitro incubation of mouse splenocytes or purified spleen cluster of differentiation (CD) 4-positive T lymphocytes, with ATRA, increased, respectively, OVA- and anti-CD 3 antibody-induced IL-4 and IL-5 production and inhibited IFNg release. These findings demonstrate that, when given during systemic sensitization, Lipo-ATRA exacerbates allergic immune and inflammatory responses, most likely by promoting Th2 development. J. Nutr. 137: 2730‐2736, 2007.

Gamma aminobutyric acid (GABA)-mediated synapses and the oscillations they orchestrate are altered in autism. GABA-acting benzodiazepines exert in some patients with autism paradoxical effects, raising the possibility that like in epilepsies, GABA excites neurons because of elevated intracellular concentrations of chloride. Following a successful pilot study,(1) we have now performed a double-blind clinical trial using the diuretic, chloride-importer antagonist bumetanide that reduces intracellular chloride reinforcing GABAergic inhibition. Sixty children with autism or Asperger syndrome (3-11 years old) received for 3 months placebo or bumetanide (1 mg daily), followed by 1-month wash out. Determination of the severity of autism was made with video films at day 0 (D0) and D90 by blind, independent evaluators. Bumetanide reduced significantly the Childhood Autism Rating Scale (CARS) (D90 - D0; P

Hairy root formation was induced by inoculating epicotyl, cotyledon and hypocotyl of Allocasuarina verticillata with two strains of Agrobacterium rhizogenes, A4 (agropine type) or 2659 (cucumopine type). Shoot regeneration from hairy roots induced by strain A4, and from control roots excised from untreated seedlings, required a hormone-enriched medium, whereas roots induced by strain 2659 spontaneously regenerated shoots on hormone-free medium. Newly formed shoots were multiplied and rooted to produce transgenic plants that developed unusually extensive, ageotropic root systems. The transformation was demonstrated by the presence of specific opines and by Southern blot analysis.

SummaryAllocasuarina verticillata, a N2-fixing tree (actinorhizal plant) reknowned for its tolerance to fire and salinity, is used for fuel wood production, land reclamation, shelter belts and for ornamental purposes. Root explants from seedlings were used for micropropagation. Biomass of regenerated shoots was increased by adding maltose (3 to 6%) instead of sucrose to Murashige and Skoog (1962) basal medium. This treatment reduced callogenesis and increased shoot number and chlorophyll content. The very high rate of shoot multiplication makes this species of Casuarinaceae a promising candidate for reforestation of arid soils in subtropical and mediterranean countries.

Gamma aminobutyric acid (GABA)-mediated synapses and the oscillations they orchestrate are altered in autism. GABA-acting benzodiazepines exert in some patients with autism paradoxical effects, raising the possibility that like in epilepsies, GABA excites neurons because of elevated intracellular concentrations of chloride. Following a successful pilot study,(1) we have now performed a double-blind clinical trial using the diuretic, chloride-importer antagonist bumetanide that reduces intracellular chloride reinforcing GABAergic inhibition. Sixty children with autism or Asperger syndrome (3-11 years old) received for 3 months placebo or bumetanide (1 mg daily), followed by 1-month wash out. Determination of the severity of autism was made with video films at day 0 (D0) and D90 by blind, independent evaluators. Bumetanide reduced significantly the Childhood Autism Rating Scale (CARS) (D90-D0; P0.004 treated vs placebo), Clinical Global Impressions (P0.017 treated vs placebo) and Autism Diagnostic Observation Schedule values when the most severe cases (CARS values above the mean ± s.d.; n=9) were removed (Wilcoxon test: P-value=0.031; Student's t-test: P-value=0.017). Side effects were restricted to an occasional mild hypokalaemia (3.0-3.5 mM l(-1) K(+)) that was treated with supplemental potassium. In a companion study, chronic bumetanide treatment significantly improved accuracy in facial emotional labelling, and increased brain activation in areas involved in social and emotional perception (Hadjikhani et al., submitted). Therefore, bumetanide is a promising novel therapeutic agent to treat autism. Larger trials are warranted to better determine the population best suited for this treatment.

The Casuarinaceae family includes about 80 species of shrubs and trees belonging to four genera, Allocasuarina,Casuarina, Ceuthostoma, and Gymnostoma. Casuarinaceae are primarily native to the Southern Hemisphere, mostly to Australia, where they occur in tropical, subtropical, and temperate coastal regions as well as in arid regions. A few species are native to the Indo-Pacific areas from Malaysia to Polynesia. All members of the family are characterized by highly reduced leaves and photosynthetic deciduous branchlets (Midgley et al. 1983; National Research Council 1984).

Acacia and Casuarina are symbiotic nitrogen-fixing tropical tree species which play a major role in large-scale afforestation programs due to their performing growth on poor soils. Genetic improvement through gene transfert technology is a valuable tool to acccelerate the production of improved tree species: long breeding cycles can be by-passed and beneficial traits such as pathogen resistance can be introduced directly. Transgenic Allocasuarina verticillata were obtained after transformation with the Agrobacterium rhizogenes strains A4 (agropine type) and 2659 (cucumopine type) (Phelep et al., 1991). Shoot regeneration occured spontaneously from roots induced by strain 2659. These transformed plants were propagated at a very high rate of shoot multiplication as described by Cao et al. (1990). Transformation of Casuarina glauca, Acacia mangium and Acacia albida has been recently initiated using wild type A. tumefaciens strain 82139 (Brasileiro et al., 1991). Both Casuarina and Acacia species were found to develop tumors after inoculation with the oncogenic Agrobacterium strain. Coinoculation experiments with 82139 and disarmed A. tumefaciens strains containing binary vectors are in progress. (Texte intégral)

To improve N, fixation in trees it is necessary not only to increase the amount of N2-fixed by the host plant in association with its symbiotic micro-organism, but also to improve the tolerance of the whole N2-fixing system to environmental stresses. This goal can be achieved through two main approaches. The first approach (clonal selection) is based on the exploitation of natural genetic variability. The selected phenotypes, vegetatively propagated by in vitro techniques and explants as diverse as young shoots, young roots, and immature female inflorescences, were succcssfull) used for micropropagation. Appropriate nutritional conditions were developed to obtain true-to-type copies of Casuarina equisetifolia, Allocasuasarina verticillata, Acacia mangi m and Acacia albida. With these species it was shown that host plant and microsymbiont strains could be selected separately. The second approach is based on genetic transformation. Transgenic plants of A. verticillata were produced using wild strains (A 4 and 2659) of Agrobacteruim rhi.zogenes. Allocasuarina verticillata is the first N2-fixing tree that has been transformed. Further studies are required to introduce genes of agronomic value into this new system. The preliminary results concerning Casuarinaceae and acacias suggest that in vitro methods are useful tools in improving other N2-fixing trees such as Prosopis spp.

Introduction Les retinoides regulent de nombreuses fonctions au niveau de l’epithelium respiratoire et des cellules impliquees dans la reaction immuno-inflammatoire allergique (lymphocytes T, cellules dendritiques, eosinophiles). Cependant, leur capacite a moduler in vivo les manifestations de l’asthme n’a pas ete etudiee. Methodes Des souris mâles de la lignee Balb/c ont ete immunisees par voie intraperitonale avec de l’ovalbumine (OVA) et provoquees 4 fois par voie intra-nasale avec du serum physiologique ou de l’OVA. Les animaux ont ete traites par voie intraperitoneale avec 10 mg/kg/jour de Lipo-ATRA, ou avec des liposomes vides, soit de facon aigue (avant chaque provocation intra-nasale), soit chronique (pendant la periode necessaire a l’immunisation et aux provocations antigeniques). Vingt-quatre heures apres la derniere provocation, l’hyperreactivite bronchique (HBR) en reponse a la metacholine, la reaction immuno-inflammatoire (IgE seriques, eosinophilie pulmonaire, liberation d’IL-4, IL-5, IL-13, eotaxine, dans le lavage bronchoalveolaire - LBA -), et le remodelage bronchique (taux de fibronectine et mucines et activites MMP-2 et MM-9 dans le LBA, contenu du collagene dans le poumon) ont ete analyses. Resultats Le Lipo-ATRA, administre de facon aigue, augmente la BHR, l’eosinophilie du LBA et du tissu, les taux seriques d’IgE et la liberation d’IL-4, IL-5, d’IL-13 et de fibronectine dans le LBA. De facon opposee, le traitement chronique avec du Lipo-ATRA inhibe l’ensemble de ces reponses. Independamment du protocole de traitement (aigu ou chronique), le Lipo-ATRA supprime la liberation d’eotaxine et augmente celle des mucines dans le LBA, mais ne modifie pas le depot pulmonaire de collagene et l’activite MMP-2 et MMP-9 dans le LBA. Conclusion Le Lipo-ATRA module positivement ou negativement l’HRB et la reponse immuno-inflammatoire allergique en fonction du moment et de la duree du traitement, suggerant une action sur des cibles cellulaires distinctes. Les effets du Lipo-ATRA au niveau de l’epithelium respiratoire (inhibition de l’eotaxine et augmentation des mucines) sont independants de ses actions opposees vis-a-vis de la reaction immuno-allergique. Enfin, dans ce modele, l’HRB et la reponse immuno-inflammatoire sont associees, mais independantes du remodelage tissulaire.

L'objectif du travail est de transformer un certain nombre d'arbres tropicaux intéressants pour le reboisement en zone sahélienne. Susceptibilité d'un vecteur biologique (Agrobacterium rhizogenes) à transformer trois arbres tropicaux fixateurs d'azote : Allocasuarina stricta, Casuarina equisetifolia, Acacia mangium. Rappel de la technique de transfert de gène (ADN exogène). Deux souches de A. rhizogenes ont été testées : une souche à agropine A4 et une souche à cucumopine NCPP2659, appelée par la suite 2659. Deux sortes d'inoculum ont été utilisées; inoculum S et inoculum L. Méthodes d'inoculation (cotylédons, hypocotyles, épicotyles). Apparition de cals et de racines sur les plants inoculés. La réponse à l'inoculation varie selon le type de souche utilisée, la nature de l'organe de la plantule inoculé, la nature liquide ou solide de la culture de Agrobacterium servant à la préparation de l'inoculum, l'addition de saccharose ou d'auxine dans le milieu de culture de l'explant