86 resultados para Uriburu, José Félix, 1930-1932


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5 cartas (manuscritas y mecanografiadas) ; 215x160mm. Ubicación: Caja 1 - Carpeta 12

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Pannexin1 (Panx1) is a plasma membrane channel permeable to relatively large molecules, such as ATP. In the central nervous system (CNS) Panx1 is found in neurons and glia and in the immune system in macrophages and T-cells. We tested the hypothesis that Panx1-mediated ATP release contributes to expression of Experimental Autoimmune Encephalomyelitis (EAE), an animal model for multiple sclerosis, using wild-type (WT) and Panx1 knockout (KO) mice. Panx1 KO mice displayed a delayed onset of clinical signs of EAE and decreased mortality compared to WT mice, but developed as severe symptoms as the surviving WT mice. Spinal cord inflammatory lesions were also reduced in Panx1 KO EAE mice during acute disease. Additionally, pharmacologic inhibition of Panx1 channels with mefloquine (MFQ) reduced severity of acute and chronic EAE when administered before or after onset of clinical signs. ATP release and YoPro uptake were significantly increased in WT mice with EAE as compared to WT non-EAE and reduced in tissues of EAE Panx1 KO mice. Interestingly, we found that the P2X7 receptor was upregulated in the chronic phase of EAE in both WT and Panx1 KO spinal cords. Such increase in receptor expression is likely to counterbalance the decrease in ATP release recorded from Panx1 KO mice and thus contribute to the development of EAE symptoms in these mice. The present study shows that a Panx1 dependent mechanism (ATP release and/or inflammasome activation) contributes to disease progression, and that inhibition of Panx1 using pharmacology or gene disruption delays and attenuates clinical signs of EAE.

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Proteolytic enzymes have evolved several mechanisms to cleave peptide bonds. These distinct types have been systematically categorized in the MEROPS database. While a BLAST search on these proteases identifies homologous proteins, sequence alignment methods often fail to identify relationships arising from convergent evolution, exon shuffling, and modular reuse of catalytic units. We have previously established a computational method to detect functions in proteins based on the spatial and electrostatic properties of the catalytic residues (CLASP). CLASP identified a promiscuous serine protease scaffold in alkaline phosphatases (AP) and a scaffold recognizing a beta-lactam (imipenem) in a cold-active Vibrio AP. Subsequently, we defined a methodology to quantify promiscuous activities in a wide range of proteins. Here, we assemble a module which encapsulates the multifarious motifs used by protease families listed in the MEROPS database. Since APs and proteases are an integral component of outer membrane vesicles (OMV), we sought to query other OMV proteins, like phospholipase C (PLC), using this search module. Our analysis indicated that phosphoinositide-specific PLC from Bacillus cereus is a serine protease. This was validated by protease assays, mass spectrometry and by inhibition of the native phospholipase activity of PI-PLC by the well-known serine protease inhibitor AEBSF (IC50 = 0.018 mM). Edman degradation analysis linked the specificity of the protease activity to a proline in the amino terminal, suggesting that the PI-PLC is a prolyl peptidase. Thus, we propose a computational method of extending protein families based on the spatial and electrostatic congruence of active site residues.

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1 tarjeta y 1 carta (manuscritas y mecanografiadas) ; entre 146x92mm y 135x215mm. Ubicación: Caja 1 - Carpeta 31

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10 cartas (manuscritas y mecanografiadas) ; entre 208x124mm y 213x275mm. Ubicación: Caja 1 - Carpeta 33

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8 cartas y 1 tarjeta postal (manuscritas y mecanografiadas) ; entre 335x227mm y 135x90mm. Ubicación: Caja 1 - Carpeta 33

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9 cartas (mecanografiadas) ; 207x300mm. Ubicación: Caja 1 - Carpeta 36

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1 carta (manuscrita) ; 270x180mm. Ubicación: Caja 1 - Carpeta 37

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8 cartas (manuscritas) y 1 carta (manuscrita y mecanografiada) ; entre 160x180mm y 320x200mm. Ubicación: Caja 1 - Carpeta 40

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1 carta (mecanografiada) ; 213x165mm. Ubicación: Caja 1 - Carpeta 43

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1 carta (mecanografiada) ; 215x135mm. Ubicación: Caja 1 - Carpeta 51

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1 carta (mecanografiada) ; 340x165mm. Ubicación: Caja 1 - Carpeta 61