80 research outputs found
Die antivirale Rolle von USP10 in Reaktion auf Chikungunya- und Mayaro-Virusinfektionen
No full textMosquito-borne alphaviruses like Chikungunya virus (CHIKV) and Mayaro virus (MAYV), which caused endemic outbreaks involving millions of patients over the past decades, pose an emerging threat due to climate-driven expansion of the virus vectors. Recently, the first vaccine against CHIKV was approved by the FDA, however, the lack of antiviral treatments underscores the need for a deeper understanding of virus-host interactions, potentially leading to the development of novel antiviral strategies.
In this thesis, we investigate the role of ubiquitin-specific protease 10 (USP10) in the context of CHIKV and MAYV. Our findings demonstrate that USP10 overexpression significantly reduces infection rates for both alphaviruses. This antiviral effect is independent of USP10's deubiquitinase activity and instead relies on its interaction with the stress granule protein G3BP, mediated by a specific motif (FGDF) within USP10. Notably, USP10 overexpression disrupts the formation of stress granules during CHIKV infection, likely by sequestering G3BP and preventing its aggregation.
Exploring the impact of USP10 on different stages of the viral replication cycle, our findings suggest that USP10 primarily targets the later stages, inhibiting the formation and release of new virus particles. In contrast, CHIKV glycoprotein-mediated entry and viral RNA replication are not significantly affected by USP10. Analogously to USP10, CHIKV nonstructural protein 3 (nsP3) binds G3BP via two FGDF motifs. Cells infected with G3BP binding-deficient mutants displayed no reduction in viral infection upon USP10 overexpression, underlining a critical role of the G3BP-nsP3 interaction in the antiviral effect of USP10.
Finally, we explored the emergence of potential escape variants after serial passaging of CHIKV under selection pressure by USP10 overexpression. Notably, mutations were observed in the nsP2 and E2 proteins, suggesting potential rescue mutations in these proteins counteracting the antiviral activity of USP10. This highlights the selective pressure exerted by USP10, highlighting its importance as an antiviral factor.
In conclusion, this thesis establishes USP10 as a potent cellular inhibitor of alphavirus infection. By targeting the G3BP-nsP3 interaction, USP10 offers a promising path for the development of novel antiviral strategies
Mechanistic Elucidation of Protease–Substrate and Protein–Protein Interactions for Targeting Viral Infections
No full textViral infections represent an old threat to global health, with multiple epidemics and pandemics in the history of mankind. Despite several advances in the development of antiviral substances and vaccines, many viral species are still not targeted. Additionally, new viral species emerge, posing a menace without precedent to humans and animals and causing fatalities, disabilities, environmental harm, and economic losses.
In this thesis, we present rational modeling approaches for targeting specific protease-substrate and protein-protein interactions pivotal for the viral replication cycle. Over the course of this work, antiviral research is supported beginning with the development of small molecular antiviral substances, going through the modeling of a potential immunogenic epitope for vaccine development, towards the establishment of descriptors for susceptibility of animals to a viral infection. Notably, all the research was done under scarce data availability, highlighting the predictive power of computational methods and complementarity between in-silico and in-vitro or in-vivo methods
A revised checklist of Hawaiian mosses
No full textA revised and updated literature-based checklist of Hawaiian mosses is presented. Geographic coverage includes the eight main Hawaiian Islands; the Northwestern Hawaiian Islands are excluded. The checklist is alphabetically ordered by scientific names; the family is noted for each genus. Synonyms and misapplied names are cross-referenced to the accepted names. A bibliography of supporting references is included
Distribution et importance quantitative de la chitine dans les coquilles de mollusques
No full textpeer reviewed1. The wide distribution of chitin in the shells of Molluscs was confirmed thanks to the application of a quantitative and specific enzymatic method. Chitin was found not only in Cephalopod shells, but also in mother-of-pearl, pseudonacreous layers, and in many cases, in periostracum and prismatic layers of Gastropod and Bivalve shells. 2. The presence and the proportion of chitin are highly variable in the periostracum of the Bivalve species studied so far. On the Contrary, its permanent presence in the organic matrix, associated with mother-of-pearl, emphasizes the homology of this structure in the whole phylum nof Mollusca. 3. The more or less important participation of chitin in the vbuilding of the organic matrix of the different shell structures may be related to taxonomic and/or ecological characteristics. From a taxonomical point of view, on the one hand, chitin distribution is in good agreement with the classification grouping Arcidae and Glycimeridae among the Filibranchia Taxodonta and isolating Nuculidae in the Protobranchia. On the other hand, the lower rate of chitin observed in the inner calcified shell layers of seven species of Anisomyaria and the high chitin rate in those of four species of Adapedonta may be a further indication of the homogeneity of both taxa. From an ecological point of view, chitin constitutes an important fraction of the shell organic matter in burrowing species, while this polysaccharide is practically lacking or in very low proportions in the shells of fixed or free species.1. Au moyen d'une méthode enzymatique hautement spécifique, la chitine a été mise en évidence et dosée chez toute une série de Mollusques, non seulement chez les Céphalopodes et au niveau de structures où sa présence était déjà connue, mais aussi dans la nacre d'autres types de strates calcifiées de la coquille de diverses espèces de Lamellibranches et de Gastéropodes ainsi que, dans certains cas, au niveau des couches de prismes et du périostracum. 2. Le périostracum diffère considérablement, chez les espèces étudiées, sous le rapport de la présence de chitine et de son importance quantitative relative. Par contre, la chitine est toujours présente dans la matrice organique de la nacre, ce qui pourrait confirmer le caractère d'homologie de cette structure à travers le phylum des Mollusques. 3. La participation de la chitine à la constitution de la matrice organique des coquilles de Bivalves peut être interprétée sous l'angle taxonomique ou écologique. D'un point de vue taxonomique, la constitution chimique du périostracum d'une part est en bon accord avec l'isolement des Nuculidae au sein des Protobranchiés, et avec le regroupement des Arcidae et des Glycimeridae parmi les Filibranchiés Taxodontes. D'autre cpart, les Adapédontes se caractérisent par une plus forte proportion de chitine dans les strates calcifiées de la coquille que chez les Anisomyaires. D'un point de vue écologique, c'est chez les espèces fuisseuses (Adapédontes, mais aussi Venus, Arca, Glycimeris) que la chitine est un constituant quantitativement important de la matrice organique du périostracum et/ou des strates calcifiées internes. Chez les espèces fixées ou libres, au contraire, la chitine manque ou n'est présente qu'en faible proportion
Ultrastructural shape and three-dimensional organization of the intracuticular canal systems in the mineralized cuticule of the green crab Carcinus maenas
No full textpeer reviewedTwo main self-contained canal systems are present in the crab mineralized cuticle. The first, or fibre canal system, is constituted by simple, unbranched vertical canals containing axially running fibres in close association with myoepidermal junctions. The second, or pore canal system, is composed of procuticular pore canals and epicuticular channels that prolong the procuticular canals. In opposition to widespread opinion, pore canals make up a three-dimensional branched system extending from the apical plasma membrane of the epidermis up to the epicuticle. Branching occurs by projections of lateral horizontal from the vertical canals at the lower level of the pigmented layer and by innumerable ramifications of epicuticular canals. In agreement with Neville's model for insects, vertical procuticular pore canals of crustacean mineralized cuticle, and also fibre canals, exhibit a twisted ribbon structure reflecting the helicoidal arrangement of the horizontal chitin-protein microfibrils. © 1987
Elaboration and ultrastructural changes of the pore canal system in the mineralized cuticle of Carcinus maenas during the molting cycle
No full textpeer reviewedTwo basic structural components are concerned in the elaboration of the pore canal system in the mineralized cuticle of the decapod crab Carcinus maenas: tubular cytoplasmic extensions originating from epidermis and vertical fibres. These components are present from the moment the first procuticular materials of the new cuticle are laid down but their organization varies according to a precise schedule during the further moult cycle stages. Cytoplasmic extensions form a complicated branching system connecting the epidermal layer with all regions of the cullcular compartment, at least transitorily. During the moult cycle the prolongation of this cellular system appears to result from two concomitant but opposite phenomena. Before ecdysis the growth of cell extensions in the proximal cuticular layers prevails over their regression at the distal level. During the post-moult period these phenomena are reversed in importance so that the pore canal system is without cytoplasmic material as soon as intermoult starts. The depositing of vertical fibres takes place in close contact with the proximal cell extension plasma membrane, which never bears dense plaques. As moult stages progress, they are gradually organized into twisted sheaths that persist throughout the intermoult. Incidentally, some fibres invade the pore canal lumen freed from cell extensions. Some aspects regarding the fine organization, the chemical composition and the functional significance of both epidermal tubular extensions or vertical fibres are also discussed in the light of previous investigations carried out on crustaceans and in other arthropods. © 1987
Organisation tridimentionnnelle et cytochimie de l'épicuticule et des systèmes canaliculaires des sclérites du crabe Carcinus maenas (Crustacé, décapode)
No full textCytochemical demonstration of acid mucopolysaccharides in the epicuticular surface coat of the crab Carcinus maenas (Crustacea, Decapoda)
No full textpeer reviewe
Aspects ultrastructuraux et fonctionnels de diverses régions cuticulaires non minéralisées d'un crustacé décapode, Carcinus maenas
No full textpeer reviewe
Human periodontal ligament fibroblast behavior on chemically conditioned dentine: an in vitro study.
No full textpeer reviewedBACKGROUND: Chemical root conditioning is widely used in an attempt to improve the outcome of regenerative periodontal surgery, but its effect on connective tissue cell proliferation and biosynthetic activity has been poorly studied. The goal of the present study was to test in vitro the consequences of conditioning human dentine by citric acid or minocycline on the behavior of attached human periodontal ligament (HPDL) cells in terms of proliferation, protein synthesis and morphological appearance. METHODS: HPDL cells were seeded on powdered human dentine, either untreated or conditioned for 3 minutes with 3% citric acid or 2.5% minocycline HCI. Scanning (SEM) and transmission (TEM) electron microscopic observations were performed, and 3H-thymidine and 3H-proline incorporation tests were used to evaluate the proliferative and the biosynthetic activities. RESULTS: Cell spreading was already evident and the penetration of cytoplasmic processes into dentinal tubules were frequently observed on all dentine types after 2 hours of attachment. After 24 hours of incubation, citric acid conditioning promoted an intense spreading of the cells, while minocycline HCI conditioning induced the formation of a dense feltwork of cellular processes. HPDL fibrolasts adherent to both types of surface-conditioned dentine exhibited a significantly higher rate of proliferation (P<0.01) as well as a significantly higher level of total protein and of collagen synthesis (P<0.01) than on untreated dentine. CONCLUSIONS: These data suggest that during periodontal surgery a conditioning of the root surface by citric acid or by minocycline HCI could promote the attachment, the proliferation, and the biosynthetic activity of HDPL, prerequisites to periodontal regeneration
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