Добірка наукової літератури з теми "Rat nu des sables"

Abstract In contrast to euthymic adult Fischer rats, immunocompromised Nu/Nu animals develop a lethal infection when inoculated with the RH strain of the protozoan Toxoplasma gondii. However, a significant period of survival is obtained when Nu/Nu rats are passively transferred with sera from 28-day infected Fischer +/+ (euthymic) animals. Specific IgE are involved since IgE-depleted sera are unable to afford such a protection. Only excreted/secreted Ag or living tachyzoites are able to induce a significant protective IgE response in intact animals. In addition, platelets or, to a lesser extent, eosinophil-rich populations from Toxoplasma infected or excreted-secreted Ag-immunized euthymic animals bear surface IgE and are cytotoxic for the parasite in vitro. Also, adoptive transfer of immune platelets confers a significant degree of protection to Toxoplasma-infected Nu/Nu animals. Our results clearly show the key role of Ag present in both living parasites and excreted-secreted Ag to induce, in this model, a protective IgE response. In addition, as in other parasitic infections, platelets and probably eosinophils are the effector cells involved in controlling parasitic dissemination during Toxoplasma infection in immunocompromised rats.

ABSTRACT Human T-cell leukemia virus type 1 (HTLV-1) has been shown to be the etiologic agent of adult T-cell leukemia (ATL), but the in vivo mechanism by which the virus causes the malignant transformation is largely unknown. In order to investigate the mechanisms of HTLV-1 leukemogenesis, we developed a rat model system in which ATL-like disease was reproducibly observed, following inoculation of various rat HTLV-1-immortalized cell lines. When previously established cell lines, F344-S1 and TARS-1, but not TART-1 or W7TM-1, were inoculated, systemic multiple tumor development was observed in adult nude (nu/nu) rats. FPM1 cells, newly established from a heterozygous (nu/+) rat syngeneic to nu/nurats, caused transient tumors only at the injection site in adult nu/nu rats, but could progressively grow in newborn nu/nu rats and metastasize in lymph nodes. The derivative cell line (FPM1-V1AX) serially passed through newbornnu/nu rats acquired the potency to grow in adultnu/nu rats. These results indicated that only some with additional changes but not all of the in vitro HTLV-1-immortalized cell lines possessed in vivo tumorigenicity. Using the syngeneic system, we further showed the inhibition of tumor development by transferring splenic T cells from immunized rats, suggesting the involvement of T cells in the regression of tumors. This novel and reproducible nude rat model of human ATL would be useful for investigation of leukemogenesis and antitumor immune responses in HTLV-1 infection.

Nucleolin is a major nucleolar phosphoprotein and is presumably involved in rDNA transcription and ribosome biosynthesis. This protein is known to be very labile and to be cleaved by endogenous proteases into many small peptides. We found that, when rat liver nucleolar suspension (Nu-1) or nucleolin-rich extract (Nu-2) was incubated under conventional conditions, polyamines and histones interacted with the nucleolin to lead to its preferential degradation to 60 kDa phosphopeptide (p60). The peptide p60 was identified as a peptide containing the N-terminal half of the nucleolin molecule, as judged from peptide-map analysis. Whereas spermine binding to the purified nucleolin was decreased by KCl concentrations above 50 mM, histones (H1, H2B and H3) were able to bind to the nucleolin in the presence of up to 300 mM KCl. A distinct difference between H1 and other histones was found in that H1 could produce p60 from nucleolin in both Nu-1 and Nu-2, whereas H2B and H3 stimulated the degradation of nucleolin to p60 only when Nu-2 was used for the source of nucleolin. A possible relationship between p60 formation and rRNA synthesis is discussed, but its exact role remains to be studied.

Comprendre comment les neurones se développent pour former le schéma organisé des connexions synaptiques reste une question centrale en neurosciences. La grande majorité des synapses excitatrices se forment tôt au cours du développement pendant une fenêtre de synaptogenèse. Les récepteurs N-méthyl-D-aspartate (NMDAR) sont depuis longtemps considérés comme un candidat important pour stimuler la synaptogenèse, car les données in vivo et in vitro montrent un rôle clé des NMDARs pendant cette phase. De plus, le fait que les NMDARs se trouvent dans les synapses « silencieuses », immatures sur le plan développemental, et parmi les premiers récepteurs à s'accumuler et s’agréger au site des synapses naissantes conduit à l'hypothèse que l'agrégation des NMDARs est un point de départ dans la formation des synapses. Cependant, les mécanismes moléculaires précoces sous-tendant l'agrégation des NMDARs en assemblages pro-synaptogéniques restent peu connus. De précédents travaux montrant que les NMDARs peuvent interagir directement avec d'autres protéines de surface, y compris des récepteurs, ont favorisé la possibilité que les interactions protéine-protéine (PPI) à la surface des neurones représentent un moyen puissant pour agréger les récepteurs. En utilisant une combinaison d'imagerie en direct et de microscopie super-résolution, nous avons observé que l'interaction entre les D1R-GluN1-NMDARs était favorisée dans les neurones immatures, pendant la phase de synaptogenèse. Nous avons montré que l'interaction D1R-GluN1-NMDAR façonne directement l'organisation des NMDARs, permettant leur agrégation fonctionnelle et la synaptogenèse. En effet, empêcher l'interaction dans les neurones immatures, et non dans les neurones matures, a altéré la formation des synapses excitatrices. Nous nous sommes ensuite concentrés sur les mécanismes de régulation intracellulaire et extracellulaire de l'interaction. Nous avons démontré un rôle des récepteurs métabotropes du glutamate (mGluR) et de la caséine kinase 1 (CK1) dans la promotion de l'interaction entre les D1Rs et les GluN1-NMDARs. D’autre part, le fait que l'acide hyaluronique (HA), l'un des principaux composants de la matrice extracellulaire (ECM), soit enrichi tôt dans le cerveau immature et régule la diffusion de surface des macromolécules ouvre l'hypothèse que l'ECM régule la capacité des NMDARs à interagir avec d'autres macromolécules de surface, y compris le D1R. Pourtant, les approches classiques se sont principalement concentrées sur la dégradation de l'ECM. Ici, nous avons visé à augmenter le contenu de l'ECM en HA en surexprimant à la fois la forme sauvage de la hyaluronane synthase de type synthase 2 de rat (HAS2) ou une forme portant les deux mutations ponctuelles présentes chez le rat-taupe nu (NMR; N178S et N301S) qui est connu pour produire de l'HA de très haut poids moléculaire (vHMW-HA). Nous avons observé que l'augmentation de la matrice entravait le développement des neurones et modifiait à la fois l'organisation et le trafic de surface des NMDARs. Ces résultats valident notre stratégie et ouvrent de nouvelles voies pour enquêter sur le rôle de l'ECM dans le développement neuronal
Understanding how neurons develop to form the organized pattern of synaptic connections remains a central question in neuroscience. The vast majority of excitatory synapses are formed early in development during a synaptogenesis window. N-methyl-D-aspartate receptors (NMDAR) have long been a strong candidate to drive synaptogenesis as both in vivo and in vitro data show a key role for NMDARs during that phase. Furthermore, the facts that NMDARs are found in the developmentally immature “silent” synapses and among the first receptors to accumulate at the site of nascent synapses together lead to the assumption that NMDAR’s clustering is a nucleation point. Yet, the mechanisms underpinning the early clustering of NMDARs into synaptogenic assemblies remain enigmatic. Evidences that NMDARs can directly interact with other surface proteins, including receptors, has promoted the possibility that surface protein-protein interaction (PPI) represents a potent way to cluster receptors. Using a combination of live imaging and super-resolution microscopy, we observed that the interaction between D1R-GluN1-NMDARs were promoted in immature neurons, during the synaptogenesis phase. We showed that the D1R-GluN1-NMDAR interaction directly shapes the organization of NMDARs, allowing their functional clustering and synaptogenesis. Indeed, preventing the interaction in immature neurons, and not in mature neurons, altered the formation of excitatory post-synapses. We then focused on the intracellular and extracellular regulatory mechanisms of the interaction. We demonstrated a role of metabotropic glutamate receptors (mGluR) and casein kinase 1 (CK1) in promoting the interaction between D1Rs and GluN1-NMDARs. On the other hand, both the fact that the hyaluronic acid (HA), one of the main components of the extracellular matrix (ECM), is enriched early in the immature brain and regulates the surface diffusion of macromolecules opens the hypothesis that the ECM regulates the ability of NMDARs to interact with other surface macromolecules, including D1R. Yet, classical approaches have mainly focused on degrading the ECM. Herein, we aimed at increasing the ECM content in HA by over-expressing both the wild-type form of the rat hyaluronan synthase 2 (HAS2) or one bearing the two point-mutations present in the naked mole rat (NMR; N178S and N301S) which produces very high molecular weight HA (vHMW-HA). We observed that increasing the matrix impaired the development of the neuron and modified both the surface organization and trafficking of NMDARs. These findings validate our strategy, and open new paths for investigating the role of the ECM on neuronal development