TAR DNA-Binding protein 43 (TDP-43) regulates stress granule dynamics via differential regulation of G3BP and TIA-1

TDP-43 est une protéine multifonctionnelle possédant des rôles dans la transcription, l'épissage des pré-ARNm, la stabilité et le transport des ARNm. TDP-43 interagit avec d'autres hnRNP, incluant hnRNP A2, via son extrémité C-terminale. Plusieurs membres de la famille des hnRNP étant impliqués dans la réponse au stress cellulaire, alors nous avons émis l’hypothèse que TDP-43 pouvait y participer aussi. Nos résultats démontrent que TDP-43 et hnRNP A2 sont localisés au niveau des granules de stress, à la suite d’un stress oxydatif, d’un choc thermique, et lors de l’exposition à la thapsigargine. TDP-43 contribue à la fois à l'assemblage et au maintien des granules de stress en réponse au stress oxydatif. TDP-43 régule aussi de façon différentielle les composants clés des granules de stress, notamment TIA-1 et G3BP. L'agrégation contrôlée de TIA-1 est perturbée en l'absence de TDP-43. En outre, TDP-43 régule le niveau d`ARNm de G3BP, un facteur de granule de stress de nucléation. La mutation associée à la sclérose latérale amyotrophique, TDP-43R361S, compromet la formation de granules de stress. Ainsi, la fonction cellulaire de TDP-43 s'étend au-delà de l’épissage; TDP-43 est aussi un composant de la réponse cellulaire au stress central et un acteur actif dans le stockage des ARNs.

Identification and characterization of a new adhesin involved in the binding of Streptococcus suis to the extracellular matrix proteins

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal

Purification and identification of specific RNA-binding protein that binds to the 3'UTR region of cytochrome P450aromatase mRNA in bovine granulosa cells

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

Les substrats neuronaux sous-tendant le binding automatique et contrôlé en mémoire de travail dans la schizophrénie : une étude en IRMf.

Le déficit de mémoire de travail est une des caractéristiques centrales de la schizophrénie et est associé aux problèmes de fonctionnement quotidien des patients. Parmi les différents processus sous-tendus par la mémoire de travail, nous nous intéressons au binding. Le binding est un processus qui permet d’associer plusieurs informations (par exemple, associer le nom d’une personne avec son adresse). En mémoire de travail, les patients schizophrènes ne présentent pas de déficit de binding lorsque les informations sont associées involontairement. Ce type de binding est appelé binding automatique. Cependant, les informations peuvent aussi être associées sous le contrôle volontaire et attentionnel des participants, nous parlons alors de binding contrôlé. À l’heure actuelle, aucune étude n’a été effectuée sur le binding contrôlé en schizophrénie. Notre objectif est de déterminer s'il existe un déficit spécifique de binding contrôlé dans la schizophrénie, et de décrire les substrats neuronaux qui le sous-tendent. Dix-neuf patients schizophrènes et 18 sujets témoins ont effectué une tâche de binding en mémoire de travail dans un scanner IRM. Celle-ci consistait à mémoriser des mots et des positions spatiales dont l’association variait selon deux conditions. Dans la condition de binding contrôlé, les mots et les positions spatiales étaient présentés séparément et les participants devaient faire l’association entre les deux informations eux-mêmes. Dans la condition de binding automatique, les mots étaient d’emblée associés aux positions spatiales. Nos résultats suggèrent que les patients schizophrènes n’auraient pas de déficit de binding automatique alors qu’ils auraient un déficit de binding contrôlé par rapport aux sujets témoins. Le déficit de binding contrôlé serait sous-tendu par des niveaux d’activation plus faibles du cortex préfrontal dorsolatéral. Les processus contrôlés seraient altérés alors que les processus automatiques seraient préservés dans la schizophrénie.

Amino acids substitutions in σ1 and μ1 outer capsid proteins of a Vero cell-adapted mammalian orthoreovirus are required for optimal virus binding and disassembly

In a recent study, the serotype 3 Dearing strain of mammalian orthoreovirus was adapted to Vero cells; cells that exhibit a limited ability to support the early steps of reovirus uncoating and are unable to produce interferon as an antiviral response upon infection. The Vero cell-adapted virus (VeroAV) exhibits amino acids substitutions in both the σ1 and μ1 outer capsid proteins but no changes in the σ3 protein. Accordingly, the virus was shown not to behave as a classical uncoating mutant. In the present study, an increased ability of the virus to bind at the Vero cell surface was observed and is likely associated with an increased ability to bind onto cell-surface sialic acid residues. In addition, the kinetics of μ1 disassembly from the virions appears to be altered. The plasmid-based reverse genetics approach confirmed the importance of σ1 amino acids substitutions in VeroAV's ability to efficiently infect Vero cells, although μ1 co-adaptation appears necessary to optimize viral infection. This approach of combining in vitro selection of reoviruses with reverse genetics to identify pertinent amino acids substitutions appears promising in the context of eventual reovirus modification to increase its potential as an oncolytic virus.

Decreased 5-HT2C receptor binding in the cerebral cortex and brain stem during pancreatic regeneration in rats

The purpose of this study was to investigate the role of central 5-HT2C receptor binding in rat model of pancreatic regeneration using 60-70% pancreatectomy. The 5-HT and 5-HT2c receptor kinetics were studied in cerebral cortex and brain stem of sham operated, 72 h pancreatectomised and 7 days pancreatectomised rats. Scatchard analysis with [3H] mesulergine in cerebral cortex showed a significant decrease (p < 0.05) in maximal binding (B^,ax) without any change in Kd in 72 h pancreatectomised rats compared with sham. The decreased Bmax reversed to sham level by 7 days after pancreatectomy. In brain stem , Scatchard analysis showed a significant decrease (p < 0.01) in Bax with a significant increase (p < 0.01) in Kd. Competition analysis in brain stem showed a shift in affinity towards a low affinity. These parameters were reversed to sham level by 7 days after pancreatectomy. Thus the results suggest that 5-HT through the 5-HT2C receptor in the brain has a functional regulatory role in the pancreatic regeneration. (Mol Cell Biochem 272: 165-170, 2005)

Decreased (x1-Adrenergic Receptor Binding in the Cerebral Cortex and Brain Stem during Pancreatic Regeneration in Rats

purpose of this study was to investigate the role of brain al-adrenergic receptor binding in the rat model of pancreatic regeneration using 60-70% pancre:dectorny. The a, -adrenergic receptors kinetics was studied in the cerebral cor:cx and brain stem of sham operated . 72 It pan- crea(ectoinised and 7 days pancreatectomised rats. Scar chard analysis with I `I I lprazocin in cerebral cartes and brain stein showed a significant decrease (/' < 0.01). (P < 0.05) in maximal binding ( 1),,,,,) with it significant decrease (P < 0.001 ), ( P < 0.01) in the K,,in 72 It pancreatecto- raised rats compared with sham , respectively . Competition analysis in cerebral cortex and brain stem showed it shift in affinity during pancreatic regeneration . The sympathetic activity was decreased as indicated by the significantly de- increased norepinephrine level in the plasma (P < 0.001), cerebral cortex (P < 0.01) and brain stem (P < 0.001) of 72 h pancreatectomised rats compared to sham . Thus, from our results it is suggested that the central a, -adrenergic receptors have a functional role in the pancreatic regenera- Lion mediated through the sympathetic pathway.

Increased 5-HT2C Receptor Binding in the Brain Stem And Cerebral Cortex During Liver Regeneration And Hepatic Neoplasia In Rats

In the present study, serotonin 2C (5-HT2c) receptor binding parameters in the brainstem and cerebral cortex were investigated during liver generation after partial hepatectomy (PH) and N-nitrosodiethylamine (NDEA) induced hepatic neoplasia in male Wistar rats. The serotonin content increased significantly (p<0.01) in the cerebral cortex after PH and in NDEA induced hepatic neoplasia. Brain stem serotonin content increased significantly (p<0.05) after PH and (p<0.001) in NDEA induced hepatic neoplasia. The number and affinity of the 5-HT2c receptors in the crude synaptic membrane preparations of the brain stem showed a significant (p<0.001) increase after PH and in NDEA induced hepatic neoplasia. The number and affinity of 5-HT2c receptors increased significantly (p<0.001) in NDEA induced hepatic neoplasia in the crude synaptic membrane preparations of the cerebral cortex. There was a significant (p<0.01) increase in plasma norepinephrine in PH and (p<0.001) in NDEA induced hepatic neoplasia, indicating sympathetic stimulation. Thus, our results suggest that during active hepatocyte proliferation 5-HT2c receptor in the brain stem and cerebral cortex are up-regulated which in turn induce hepatocyte proliferation mediated through sympathetic stimulation.

Decreased [ 3 H] YM-09151-2 binding to dopamine D2 receptors in the hypothalamus, brainstem and pancreatic islets of streptozotocin -induced diabetic rats

In the present study dopamine was measured in the hypothalamus, brainstem, pancreatic islets and plasma, using HPLC. Dopamine D2 receptor changes in the hypothalamus, brainstem and pancreatic islets were studied using [3H] YM-09151-2 in streptozotocin-induced diabetic and insulintreated diabetic rats. There was a significant decrease in dopatnine content in the hypothalamus (P<0.001), brainstem (P<0.001), pancreatic islets (P<0.001) and plasma (P<0.00I) in diabetic rats when compared to control. Scatchard analysis of [3H] YM-09151-2 in the hypothalamus of diabetic rats showed a significant decrease in Bax (P<0.001) and Kd, showing an increased affinity of D2 receptors when compared to control. Insulin treatment did not completely reverse the changes that occurred during diabetes. There was a significant decrease in B,nax (P<0.01) with decreased affinity in the brainstem of diabetic rats. The islet membrane preparation of diabetic rats showed a significant decrease (P<0.001) in the binding of [3H] YM-09 151-2 with decreased Kd (P<0.001) compared to control. The increase in affinity of D2 receptors in hypothalamus and pancreatic islets and the decreased affinity in brainstem were confirmed by competition analysis. Thus our results suggest that the decreased dopamine D, receptor function in the hypothalamus, brainstem and pancreas affects insulin secretion in diabetic rats, which has immense clinical relevance to the management of diabetes.

Enhancement of [m-methoxy 3H]MDL100907 binding to 5HT 2A receptors in cerebral cortex and brain stem of streptozotocin induced diabetic rats

5-Hydroxytryptamine2A (5-HT2A) receptor kinetics was studied in cerebral cortex and brain stem of streptozotocin (STZ) induced diabetic rats. Scatchard analysis with [3H] (±) 2,3dimethoxyphenyl-l-[2-(4-piperidine)-methanol] ([3H]MDL100907) in cerebral cortex showed no significant change in maximal binding (Bmax) in diabetic rats compared to controls. Dissociation constant (K) of diabetic rats showed a significant decrease (p < 0.05) in cerebral cortex, which was reversed to normal by insulin treatment. Competition studies of [3H]MDL100907 binding in cerebral cortex with ketanserin showed the appearance of an additional low affinity site for 5-HT2A receptors in diabetic state, which was reversed to control pattern by insulin treatment. In brain stem, scatchard analysis showed a significant increase (p < 0.05) in Bmax accompanied by a significant increase (p < 0.05) in Kd. Competition analysis in brain stem also showed a shift in affinity towards a low affinity State for 5-HT2A receptors. All these parameters were reversed to control level by insulin treatment. These results show that in cerebral cortex there is an increase in affinity of 5-HT2A receptors without any change in its number and in the case of brain stem there is an increase in number of 5HT2A receptors accompanied by a decrease in its affinity during diabetes. Thus, from the results we suggest that the increase in affinity of 5-HT2A receptors in cerebral cortex and upregulation of 5-HT2A receptors in brain stem may lead to altered neuronal function in diabetes.

Enhancement Of High Affinity Y-Aminobutyric Acid Receptor Binding In Cerebellum Of Pyridoxine-Deficient Rat

The high-affinity of [3H]y-aminobutyric acid (GABA) to GABAA receptors and [3H]baclofen to GABAB receptors were studied in the cerebellum of pyridoxine-deficient rats and compared to pyridoxine-supplemented controls. There was a significant increase in the maximal binding ( Bmax) of both GABAA and GABAB receptors with no significant difference in their binding affinities (Kd). The changes observed suggest a supersensitivity of GABAA and GABAB receptors which seems to correlate negatively with the concentration of GABA in the cerebellum of pyridoxine-deficient rats.

Studies on Mastication Stage Binding of Antioxidants

Paraphenylenediamine and diphenylamine were chemically attached to natural rubber during mastication . The rubber bound antioxidants were characterized by TLC, 'H-NMR, IR and TGA. The efficiency and permenance of these bound antioxidants were compared with a conventional amine type antioxidant in filled natural rubber vulcanizates . The rubber bound antioxidants were found to be less volatile and less extractable as compared to conventional antioxidants. The vulcanizates showed improved ageing resistance as compared to vulcanizates containing conventional antioxidants. This semisolid rubber bound antioxidant can reduce the amount of plasticizer required for compounding.

Elastic Constants And Structural Parameters Of Selected Polycrystalline Ceramics By Ultrasonic Technique

The present work is an attempt to probe the elastic properties in some dielectric ceramics, by using ultrasonic pulse echo overlap technique. The base Ba6-xSm8+2xTi18O54 and Ca5Nb2TiO12 are very important dielectrics ceramics used for microwave communication as well as for substrate materials. Ultrasonic is one of the most widely used and powerful techniques to measure elastic properties of solids. The ultrasonic technique is nondestructive in nature and the measurements are relatively straightforward to perform. One unique advantantage of the ultrasonic technique is that both static and dynamic properties can be measured simultaneously. The velocity and attenuation coefficients of the ultrasonic waves propagating through a medium are related to the microscopic structure of the material and they provide valuable information about the structural changes in the system. Among the various ultrasonic techniques, the pulse echo overlap method is the most accurate and precise one. In the present case the decreased elastic properties of Cas-XMg,Nb2TiO12 and Cas-,ZnNb2TiO12 ceramics can be attributed to their mixture phases beyond x = 1. Moreover, the abrupt change in elastic properties observed for x >1 can also be correlated to the structural transformation of the materials from their phase pure form to mixture phases for higher extent of substitution of the concerned material . Ca4(ANb2Ti)012 (A = Mg, Zn) is the strongest compound with the maximum values for elastic properties . This could be due to the possible substitution of Mg/Zn ions with lesser radius [25] than Ca2+ in perovskite B-site of Ca(Cali4Nb2i4Tili4) O3 material to contribute more ordering and symmetry to the system [20]. All other compositions (x > 1) contain mixed-phases and for such mixed-phase samples, the mechanical properties are difficult to explain.

Ultrasonic measurement of the elastic constants of selected nonlinear optical /semiorganic crystals with orthorhombic symmetry

Ultrasonic is a good tool to investigate the elastic properties of crystals. It enables one to determine all the elastic constants, Poisson’s ratios, volume compressibility and bulk modulus of crystals from velocity measurements. It also enables one to demonstrate the anisotropy of elastic properties by plotting sections of the surfaces of phase velocity, slowness, group velocity, Young’s modulus and linear compressibility along the a-b, b-c and a-c planes. They also help one to understand more about phonon amplification and help to interpret various phenomena associated with ultrasonic wave propagation, thermal conductivity, phonon transport etc. Study of nonlinear optical crystals is very important from an application point of view. Hundreds of new NLO materials are synthesized to meet the requirements for various applications. Inorganic, organic and organometallic or semiorganic classes of compounds have been studied for several reasons. Semiorganic compounds have some advantages over their inorganic and inorganic counterparts with regard to their mechanical properties. High damage resistance, high melting point, good transparency and non-hygroscopy are some of the basic requirements for a material to be suitable for device fabrication. New NLO materials are being synthesized and investigation of the mechanical and elastic properties of these crystals is very important to test the suitability of these materials for technological applications