ABSTRACT
Cyclophilin A (CyPA, also known as PPIA) is an abundant and ubiquitously expressed protein belonging to the immunophilin family, which has intrinsic peptidyl-prolyl-(cis/trans)-isomerase enzymatic activity. CyPA mediates immunosuppressive action of the cyclic undecapeptide cyclosporine A and is also involved in multiple cellular processes, such as protein folding, intracellular trafficking, signal transduction and transcriptional regulation. CyPA is abundantly expressed in cancer cells, and, owing to its chaperone nature, its expression is induced upon the onset of stress. In this study, we demonstrated that a significant pool of this immunophilin is primarily an intramitochondrial factor that migrates to the nucleus when cells are stimulated with stressors. CyPA shows anti-apoptotic action per se and the capability of forming ternary complexes with cytochrome c and the small acidic co-chaperone p23, the latter interaction being independent of the usual association of p23 with the heat-shock protein of 90â kDa, Hsp90. These CyPAâ¢p23 complexes enhance the anti-apoptotic response of the cell, suggesting that both proteins form a functional unit, the high level of expression of which plays a significant role in cell survival.
Subject(s)
Apoptosis , Cyclophilin A , Cyclosporine , 3T3 Cells , Animals , Carrier Proteins , Cyclophilin A/genetics , Cyclophilin A/metabolism , HeLa Cells , Humans , Mice , Peptidylprolyl Isomerase , Protein Folding , RatsABSTRACT
El manejo clínico y epidemiológico de los pacientes con fibrosis quística (FQ) con exacerbaciones pulmonares agudas o infecciones pulmonares crónicas demanda una actualización permanente de procedimientos médicos y microbiológicos, estos se asocian con la constante evolución de los agentes patógenos durante la colonización de su hospedador. Para poder monitorear la dinámica de estos procesos es fundamental disponer de sistemas expertos que permitan almacenar, extraer y utilizar la información generada a partir de estudios realizados sobre el paciente y los microorganismos aislados de aquel. En este trabajo hemos diseñado y desarrollado una base de datos on-line basada en un sistema informático que permite el almacenamiento, el manejo y la visualización de la información proveniente de estudios clínicos y de análisis microbiológicos de bacterias obtenidas del tracto respiratorio del paciente con FQ. Este sistema informático fue designado como Cystic Fibrosis Cloud database (CFC database) y está disponible en el sitio http://servoy.infocomsa.com/cfc_database. Está compuesto por una base de datos principal y una interfaz on-line, la cual emplea la arquitectura de productos Servoy basada en tecnología Java. Si bien el sistema CFC database puede ser implementado como un programa local de uso privado en los centros de asistencia a pacientes con FQ, admite también la posibilidad de ser empleado, actualizado y compartido por diferentes usuarios, quienes pueden acceder a la información almacenada de manera ordenada, práctica y segura. La implementación del CFC database podría tener una gran impacto en la monitorización de las infecciones respiratorias, la prevención de exacerbaciones, la detección de organismos emergentes y la adecuación de las estrategias de control de infecciones pulmonares en pacientes con FQ
The epidemiological and clinical management of cystic fibrosis (CF) patients suffering from acute pulmonary exacerbations or chronic lung infections demands continuous updating of medical and microbiological processes associated with the constant evolution of pathogens during host colonization. In order to monitor the dynamics of these processes, it is essential to have expert systems capable of storing and subsequently extracting the information generated from different studies of the patients and microorganisms isolated from them. In this work we have designed and developed an on-line database based on an information system that allows to store, manage and visualize data from clinical studies and microbiological analysis of bacteria obtained from the respiratory tract of patients suffering from cystic fibrosis. The information system, named Cystic Fibrosis Cloud database is available on the http://servoy.infocomsa.com/cfc_database site and is composed of a main database and a web-based interface, which uses Servoy's product architecture based on Java technology. Although the CFC database system can be implemented as a local program for private use in CF centers, it can also be used, updated and shared by different users who can access the stored information in a systematic, practical and safe manner. The implementation of the CFC database could have a significant impact on the monitoring of respiratory infections, the prevention of exacerbations, the detection of emerging organisms, and the adequacy of control strategies for lung infections in CF patients
Subject(s)
Information Storage and Retrieval/methods , Cystic Fibrosis/physiopathology , Cystic Fibrosis/microbiology , Data Visualization , Database , Data Management/organization & administration , Monitoring, Physiologic/methodsABSTRACT
The epidemiological and clinical management of cystic fibrosis (CF) patients suffering from acute pulmonary exacerbations or chronic lung infections demands continuous updating of medical and microbiological processes associated with the constant evolution of pathogens during host colonization. In order to monitor the dynamics of these processes, it is essential to have expert systems capable of storing and subsequently extracting the information generated from different studies of the patients and microorganisms isolated from them. In this work we have designed and developed an on-line database based on an information system that allows to store, manage and visualize data from clinical studies and microbiological analysis of bacteria obtained from the respiratory tract of patients suffering from cystic fibrosis. The information system, named Cystic Fibrosis Cloud database is available on the http://servoy.infocomsa.com/cfc_database site and is composed of a main database and a web-based interface, which uses Servoy's product architecture based on Java technology. Although the CFC database system can be implemented as a local program for private use in CF centers, it can also be used, updated and shared by different users who can access the stored information in a systematic, practical and safe manner. The implementation of the CFC database could have a significant impact on the monitoring of respiratory infections, the prevention of exacerbations, the detection of emerging organisms, and the adequacy of control strategies for lung infections in CF patients.
Subject(s)
Cloud Computing , Cystic Fibrosis , Databases, Factual , Cystic Fibrosis/complications , Humans , Respiratory Tract Infections/etiologyABSTRACT
The aim of this study was to determine whether early demyelination can impact behavior in young adulthood. For this purpose, albino Wistar rats of either sex were exposed to cuprizone (CPZ) in two different intoxication protocols: one group was intoxicated before weaning (CPZ-BW), from postnatal day 7 (P7) to P21, through maternal milk, whereas the other group was intoxicated after weaning (CPZ-AW), from P21 to P35. After treatment, rats were returned to a normal diet until P90 when behavioral studies were performed. Both treatments produced marked demyelination in the corpus callosum and retraction of cortical myelin fibers. The subsequent normal diet allowed for effective remyelination at P90. Interestingly, CPZ-AW correlated with significant behavioral and neurochemical changes in a gender-dependent manner. CPZ-AW treatment altered both the number of social activities and the latency to the first social interaction in males, while also highly compromising recognition-related activities. In addition, only P90 males treated AW showed a hyperdopaminergic striatum, confirmed by an increase in tyrosine hydroxylase expression and in dopamine levels. Our results suggest that the timing of demyelination significantly influences the development of altered behavior, particularly in adult males.