Rabies immunoglobulin: brief history and recent experiences in Côte D'Ivoire

Rabies is a fatal viral zoonosis mainly transmitted via dog bites. The estimated 59'000 annual deaths caused by the disease are preventable through correct and timely administration of post-exposure prophylaxis (PEP). PEP should be initiated as soon as possible after an exposure to a rabies suspected animal and consists of a course of active vaccinations and administration of rabies immunoglobulin (RIG) in case of severe exposure. However, RIG is not accessible in most rabies endemic countries and its impact on survival in combination with modern vaccines and its cost-effectiveness is unclear. We examined the effect of equine RIG (eRIG) in a field-trial in Côte d'Ivoire, a developing country with low but chronic rabies burden and persistent lack of RIG, similar to a majority of rabies endemic countries attempting elimination of the disease.; Data from 3367 patients attending anti-rabies centers (Centres Anti-Rabiques, CARs) of the National Institute for Public Hygiene (Institut National d'Hygiène Publique, INHP) in the departments of Bouaké and San Pédro in Côte d'Ivoire was prospectively collected between April 2016 and March 2018. We identified 1594 patients at risk of rabies infection as eligible for RIG administration. Depending on local availability of eRIG and vaccination protocol applied, PEP consisted of active immunization only (non-eRIG group, n = 1145) or active and passive immunization (eRIG group, n = 449). Patients were followed-up by phone interviews at least 15 months after their exposure to assess for rabies suspected deaths.; Follow-up data was available for 641 patients in the non-eRIG group (56%) and 242 in the eRIG group (54%). Three suspected or possible rabies deaths occurred in each of the two groups, corresponding to a possible rabies mortality of 1.2% (95% CI 0.3-3.6%) in the eRIG group and 0.5% (95% CI 0.1-1.4%) in the non-eRIG group. The difference in proportions was small and not statistically significant (0.7%, p = 0.21). Deaths in both groups were associated with treatment delay after exposure and non-compliance to PEP protocol. No death occurred after correct and timely active immunization independent of eRIG administration.; The provision of eRIG did not lead to a measurable reduction of rabies burden in our study population. This underlines that improved access to active vaccines will be effective in reducing rabies deaths even if access to eRIG remains difficult in developing countries. A possible benefit of eRIG administration for severely exposed patients cannot be excluded based on these results

Estimation of dog population and dog bite risk factors in departments of San Pedro and Bouake in Côte d'Ivoire

Rabies is endemic in Côte d'Ivoire and was identified in January 2017 as a priority zoonosis by all stakeholders in public health. A well-designed integrated national rabies control is essential to attain the objective of zero human deaths from dog rabies by 2030. The current study describes the complementary elements of dog bite risk factors and the dog population estimate that are relevant for planning sustainable interventions. We conducted a transverse survey in 8'004 households in the departments of San Pedro (4'002) and Bouaké (4'002), covering both rural and urban areas. The dog-household ratio was estimated at one dog for three households (0.33) or one dog for 20 people (0.05). The owned canine population on a national level was estimated at 1'400'654 dogs (range 1'276'331 to 1'535'681). The main dog bite risk factors were dog ownership, being male, and living in urban San Pedro Department. The results lay a foundation for public engagement and further steps for mass vaccination of the household dog population to reach vaccination coverage of at least 80%. Stakeholders further recommend raising awareness of dog owners, reinforcing knowledge in school children and young boys, and behavior changes towards domestic animals

De novo variants predicting haploinsufficiency for DIP2C are associated with expressive speech delay.

The disconnected (disco)-interacting protein 2 (DIP2) gene was first identified in D. melanogaster and contains a DNA methyltransferase-associated protein 1 (DMAP1) binding domain, Acyl-CoA synthetase domain and AMP-binding sites. DIP2 regulates axonal bifurcation of the mushroom body neurons in D. melanogaster and is required for axonal regeneration in the neurons of C. elegans. The DIP2 homologues in vertebrates, Disco-interacting protein 2 homolog A (DIP2A), Disco-interacting protein 2 homolog B (DIP2B), and Disco-interacting protein 2 homolog C (DIP2C), are highly conserved and expressed widely in the central nervous system. Although there is evidence that DIP2C plays a role in cognition, reports of pathogenic variants in these genes are rare and their significance is uncertain. We present 23 individuals with heterozygous DIP2C variants, all manifesting developmental delays that primarily affect expressive language and speech articulation. Eight patients had de novo variants predicting loss-of-function in the DIP2C gene, two patients had de novo missense variants, three had paternally inherited loss of function variants and six had maternally inherited loss-of-function variants, while inheritance was unknown for four variants. Four patients had cardiac defects (hypertrophic cardiomyopathy, atrial septal defects, and bicuspid aortic valve). Minor facial anomalies were inconsistent but included a high anterior hairline with a long forehead, broad nasal tip, and ear anomalies. Brainspan analysis showed elevated DIP2C expression in the human neocortex at 10-24 weeks after conception. With the cases presented herein, we provide phenotypic and genotypic data supporting the association between loss-of-function variants in DIP2C with a neurocognitive phenotype

Yeast Mitochondrial Biogenesis: A Role for the PUF RNA-Binding Protein Puf3p in mRNA Localization

The asymmetric localization of mRNA plays an important role in coordinating posttranscriptional events in eukaryotic cells. We investigated the peripheral mitochondrial localization of nuclear-encoded mRNAs (MLR) in various conditions in which the mRNA binding protein context and the translation efficiency were altered. We identified Puf3p, a Pumilio family RNA-binding protein, as the first trans-acting factor controlling the MLR phenomenon. This allowed the characterization of two classes of genes whose mRNAs are translated to the vicinity of mitochondria. Class I mRNAs (256 genes) have a Puf3p binding motif in their 3'UTR region and many of them have their MLR properties deeply affected by PUF3 deletion. Conversely, mutations in the Puf3p binding motif alter the mitochondrial localization of BCS1 mRNA. Class II mRNAs (224 genes) have no Puf3p binding site and their asymmetric localization is not affected by the absence of PUF3. In agreement with a co-translational import process, we observed that the presence of puromycin loosens the interactions between most of the MLR-mRNAs and mitochondria. Unexpectedly, cycloheximide, supposed to solidify translational complexes, turned out to destabilize a class of mRNA-mitochondria interactions. Classes I and II mRNAs, which are therefore transported to the mitochondria through different pathways, correlated with different functional modules. Indeed, Class I genes code principally for the assembly factors of respiratory chain complexes and the mitochondrial translation machinery (ribosomes and translation regulators). Class II genes encode proteins of the respiratory chain or proteins involved in metabolic pathways. Thus, MLR, which is intimately linked to translation control, and the activity of mRNA-binding proteins like Puf3p, may provide the conditions for a fine spatiotemporal control of mitochondrial protein import and mitochondrial protein complex assembly. This work therefore provides new openings for the global study of mitochondria biogenesis

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Stratégies de travail du sol économes en énergie dans les systèmes de culture en agriculture biologique : détection, élaboration, évaluation multicritères a priori

Les agriculteurs évoquent des besoins en matière de recherches scientifiques sur la question du travail du sol sans labour en agriculture biologique pour des raisons agronomiques, environnementales (limitation de gaz à effet de serre) et économiques (limitation de la consommation énergétique). Cette étude a consisté à (i) détecter des stratégies de travail du sol innovantes économes en énergie par le biais d'enquêtes chez les agriculteurs, (ii) réaliser une typologie de ces stratégies, (iii) élaborer des stratégies à évaluer a priori, selon 3 critères (la consommation énergétique, l'impact sur la population de vulpins des champs et sur la structure du sol) à l'aide de modèles dans les conditions pédo-climatiques lorraines et (iv) classer ces stratégies sur la base d'une évaluation a priori multicritères (gestion des adventices, stabilité structurale, consommation énergétique). A partir des enquêtes, nous pouvons dire qu'il existe une diversité de pratiques de travail du sol dans les systèmes de grandes cultures biologiques. Nous avons établis 4 types de stratégies de travail du sol pour décrire cette diversité, à savoir deux stratégies "biologiques" et deux stratégies "mécaniques", correspondant à un remplacement progressif d'un travail du sol naturel, par la faune qu'il héberge, par un travail du sol mécanique d'intensité croissante... Partant de cette typologie, 5 stratégies "mécaniques" ont ensuite été conçues à l'aide d'un groupe d'experts lorrains et évaluées a priori à l'aide de modèles dans les conditions pédo-climatiques lorraines (labour systématique, non labour avec travail du sol à profondeur de travail constante, non labour avec travail du sol à profondeur croissante, non labour avec travail du sol à profondeur décroissante et non labour avec fréquence de travail du sol élevée). La stratégie de travail du sol non labour avec augmentation de la profondeur de travail du sol au cours des passages s'est révélée être la stratégie la plus pertinente lorsque nous accordons une importance égale à l'économie d'énergie, le salissement de la parcelle par les vulpins des champs et la structure du sol. Il est maintenant nécessaire de vérifier cette affirmation par le test de cette stratégie en parcelle expérimental

Up-Regulation of Astrocytic Fgfr4 Expression in Adult Mice after Spinal Cord Injury

Spinal cord injury (SCI) leads to persistent neurological deficits without available curative treatment. After SCI astrocytes within the lesion vicinity become reactive, these undergo major morphological, and molecular transformations. Previously, we reported that following SCI, over 10% of resident astrocytes surrounding the lesion spontaneously transdifferentiate towards a neuronal phenotype. Moreover, this conversion is associated with an increased expression of fibroblast growth factor receptor 4 (Fgfr4), a neural stem cell marker, in astrocytes. Here, we evaluate the therapeutic potential of gene therapy upon Fgfr4 over-expression in mature astrocytes following SCI in adult mice. We found that Fgfr4 over-expression in astrocytes immediately after SCI improves motor function recovery; however, it may display sexual dimorphism. Improved functional recovery is associated with a decrease in spinal cord lesion volume and reduced glial reactivity. Cell-specific transcriptomic profiling revealed concomitant downregulation of Notch signaling, and up-regulation of neurogenic pathways in converting astrocytes. Our findings suggest that gene therapy targeting Fgfr4 over-expression in astrocytes after injury is a feasible therapeutic approach to improve recovery following traumatism of the spinal cord. Moreover, we stress that a sex-dependent response to astrocytic modulation should be considered for the development of effective translational strategies in other neurological disorders

Le modèle Dexi-SH* pour une évaluation multicritère de la durabilité agro-écologique des systèmes d’élevage bovins laitiers herbagers

Le modèle Dexi-SH* est un modèle d'évaluation multicritère ex ante de la durabilité agro-écologique des systèmes d'élevage bovins laitiers herbagers. La structuration de l'arbre hiérarchique s'est inspiré de celui du modèle Masc (Sadok et al., 2007). L'objectif de la durabilité agro-écologique a été désagrégé en trois sous-objectifs : la durabilité des ressources biotiques, la durabilité des ressources abiotiques et les risques sur l'environnement. Ces sous-objectifs ont été déclinés en critères d'évaluation, renseignés par (i) des indicateurs issus de connaissances scientifiques ou (ii) des critères établis par la consultation d'experts. Le choix des critères d'évaluation et leurs modalités d'agrégation ont été discutés au sein d'un groupe pluridisciplinaire de scientifiques. Le modèle permet d'évaluer ex ante les systèmes d'élevage dans de nombreuses situations pédo-climatiques. La vision de la durabilité peut être modulée par l'utilisateur du modèle en modifiant les pondérations

Le modèle Dexi-SH* pour une évaluation multicritère de la durabilité agro-écologique des systèmes d'élevage laitier herbager

Format du poster : A0absen