78 research outputs found
Capacity building efforts for rabies diagnosis in resource-limited countries in Sub-Saharan Africa: a case report of the central veterinary laboratory in Benin (Parakou)
Rabies has been listed as a priority zoonotic disease in many African countries and the countdown to reach the goal of eliminating dog-mediated human rabies deaths by 2030 means that disease control measures need to be applied fast. In this context, an essential pillar of any national plan to control rabies is the implementation of reliable diagnostic techniques to ensure the success of field surveillance systems. Although many African countries have received international support for the control of rabies-some countries, like Benin, have not received a similar level of support. Indeed, until 2018, Benin was not able to diagnose rabies and rabies diagnosis in animals as well as humans relied solely on observed clinical symptoms. Although the Central Veterinary Laboratory (CVL) of Parakou had the equipment to implement two recommended tests, the lack of specific reagents and skills prevented the implementation of a rabies diagnostic service. Here we present the joint efforts of the national authorities in Benin, intergovernmental agencies, and non-governmental organizations to assess the strengths and weaknesses of the government's rabies control efforts. We have applied the Stepwise Approach toward Rabies Elimination (SARE) analysis, implemented rabies diagnostic capacities at the CVL of Parakou, characterized strains of rabies virus circulating in Benin, and finally integrated an inter-laboratory comparison program
CO adsorption on neutral iridium clusters
The adsorption of carbon monoxide on neutral iridium clusters in the size
range of n = 3 to 21 atoms is investigated with infrared multiple photon
dissociation spectroscopy. For each cluster size only a single v(CO) band is
present with frequencies in the range between 1962 cm-1 (n = 8) and 1985 cm-1
(n = 18) which can be attributed to an atop binding geometry. This behaviour is
compared to the CO binding geometries on clusters of other group 9 and 10
transition metals as well as to that on extended surfaces. The preference of Ir
for atop binding is rationalized by relativistic effects on the electronic
structure of the later 5d metals
Pairing-up viologen cations and dications: a microscopic investigation of van der Waals interactions
Tritopic NHC Precursors: Unusual Nickel Reactivity and Ethylene Insertion into a C(sp3)-H Bond
Quantum Chemical Interpretation of Ultrafast Luminescence Decay and Intersystem Crossings in Rhenium(I) Carbonyl Bipyridine Complexes
Deciphering the molecular basis of ferroportin resistance to hepcidin: Structure/function analysis of rare SLC40A1 missense mutations found in suspected hemochromatosis type 4 patients
International audienceGenetic medicine applied to the study of hemochromatosis has identified the systemic loop controlling iron homeostasis, centered on hepcidin-ferroportin interaction. Current challenges are to dissect the molecular pathways underlying liver hepcidin synthesis in response to circulatory iron, HFE, TFR2, HJV, TMPRSS6 and BMP6 functions, and to define the major structural elements of hepcidin-ferroportin interaction. We built a first 3D model of human ferroportin structure, using the crystal structure of EmrD, a bacterial drug efflux transporter of the Major Facilitator Superfamily, as template. The model enabled study of disease-associated mutations, and guided mutagenesis experiments to determine the role of conserved residues in protein stability and iron transport. Results revealed novel amino acids that are critical for the iron export function and the hepcidin-mediated inhibition mechanism: for example, tryptophan 42, localized in the extracellular end of the ferroportin pore and involved in both biological functions. Here, we propose a strategy that is not limited to structure analysis, but integrates information from different sources, including human disease-associated mutations and functional in vitro assays. The first major hypothesis of this PhD thesis is that ferroportin resistance to hepcidin relies on different molecular mechanisms that are critical for ferroportin endocytosis, and include at least three fundamental steps: (i) hepcidin binding to ferroportin, (ii) structural reorganization of the N- and C-ter ferroportin lobes, and (iii) ferroportin ubiquitination.L’étude des formes rares d’hémochromatose a contribué à une meilleure connaissance des mécanismes cellulaires et systémiques qui participent au maintien de l’homéostasie du fer et qui dépendent de l’axe hepcidine-ferroportine. Des questions fondamentales majeures restent posées sur les voies d’activation de la synthèse d’hepcidine en fonction de la quantité de fer plasmatique et de l’action à la surface des hépatocytes des protéines HFE, TFR2, HJV, TMPRSS6 et BMP6, ainsi que sur les bases structurales de l’interaction hepcidine-ferroportine. Nous avons construit un premier modèle tridimensionnel de la ferroportine humaine à partir de la structure cristallographiée d’EmrD, un exportateur de drogues bactérien qui appartient à la famille des transporteurs secondaires MFS (« Major Facilitator Superfamily »). Cette modélisation a permis, en lien avec l’étude fonctionnelle de mutations faux-sens identifiées chez des patients présentant des phénotypes typiques d’hémochromatose de type 4, d’identifier des acides aminés qui ont une fonction critique dans la stabilité de la ferroportine, la fonction d’export du fer, ou la régulation par l’hepcidine. Le tryptophane en position 42 s’est, par exemple, révélé important à la fois pour la prise en charge du fer et l’endocytose de la ferroportine à la suite de la fixation de l’hepcidine. Nous proposons ici une stratégie qui combine analyses structurales, corrélations génotype/phénotype et tests fonctionnels in vitro. Ce travail de thèse vise à révéler les différents mécanismes moléculaires qui sous-tendent le processus de dégradation de la ferroportine. Ce processus semble comprendre trois étapes essentielles : (i) fixation de l’hepcidine à la ferroportine, (ii) réorganisation structurale des lobes N et C-terminaux de la ferroportine, et (iii) ubiquitination et internalisation du transporteur
Proton dynamics in titanium(IV) sulfide-ammonia: a new model for ammoniated transition metal dichalcogenides
Critical Analysis of Association Constants between Calixarenes and Nitroaromatic Compounds Obtained by Fluorescence. Implications for Explosives Sensing
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