RESUMO
Entamoeba histolytica is a protozoan parasite that belongs to the Amoebozoa supergroup whose study related to the nucleocytoplasmic transport of proteins through the nucleus is poorly studied. In this work, we have performed in silico predictions of the potential nuclear localization signals (NLS) corresponding to the proteome of 8201 proteins from Entamoeba histolytica annotated in the AmoebaDB database. We have found the presence of monopartite nuclear localization signals (MNLSs), bipartite nuclear localization signals (BNLSs), and non-canonical monopartite NLSs with lengths exceeding 20 amino acid residues. Additionally, we detected a new type of NLS consisting of multiple juxtaposed bipartite NLSs (JNLSs) that have not been described in any eukaryotic organism. Also, we have generated consensus sequences for the nuclear import of proteins with the NLSs obtained. Docking experiments between EhImportin α and an MNLS, BNLS, and JNLS outlined the interacting residues between the Importin and cargo proteins, emphasizing their putative roles in nuclear import. By transfecting HA-tagged protein constructs, we assessed the nuclear localization of MNLS (U1A and U2AF1), JMNLS (U2AF2), and non-canonical NLS (N-terminus of Pol ll) in vivo. Our data provide the basis for understanding the nuclear transport process in E. histolytica.
RESUMO
Entamoeba histolytica, the causative agent of amebiasis, is the third leading cause of death among parasitic diseases globally. Its life cycle includes encystation, which has been mostly studied in Entamoeba invadens, responsible for reptilian amebiasis. However, the molecular mechanisms underlying this process are not fully understood. Therefore, we focused on the identification and characterization of Myb proteins, which regulate the expression of encystation-related genes in various protozoan parasites. Through bioinformatic analysis, we identified 48 genes in E. invadens encoding MYB-domain-containing proteins. These were classified into single-repeat 1R (20), 2R-MYB proteins (27), and one 4R-MYB protein. The in-silico analysis suggests that these proteins are multifunctional, participating in transcriptional regulation, chromatin remodeling, telomere maintenance, and splicing. Transcriptomic data analysis revealed expression signatures of eimyb genes, suggesting a potential orchestration in the regulation of early and late encystation-excystation genes. Furthermore, we identified probable target genes associated with reproduction, the meiotic cell cycle, ubiquitin-dependent protein catabolism, and endosomal transport. In conclusion, our findings suggest that E. invadens Myb proteins regulate stage-specific proteins and a wide array of cellular processes. This study provides a foundation for further exploration of the molecular mechanisms governing encystation and unveils potential targets for therapeutic intervention in amebiasis.
Assuntos
Amebíase , Entamoeba histolytica , Entamoeba , Humanos , Entamoeba/genética , Entamoeba/metabolismo , Entamoeba histolytica/genética , Perfilação da Expressão Gênica , Regulação da Expressão GênicaRESUMO
El objetivo del trabajo es medir los costos reales asociados a las patologías tratadas en las Unidades de Cuidados Intensivos Adulto de los Hospitales Públicos de la Región del Maule, y compararlos con el costo asignado por Fonasa al día cama para el año 2011. Materiales y métodos: Se trata de un estudio prospectivo, aplicando el Sistema de Costos Basado en Actividades (ABC). Se incluyó 469 pacientes, 222 pacientes de la Unidad de Cuidados Intensivos del Hospital de Curicó y 247 pacientes la Unidad de Cuidados Intensivos del Hospital de Talca entre el 01 de enero y 30 de agosto de 2011, los que de acuerdo a edad y APACHE, representan los niveles de complejidad de pacientes de Unidades de Cuidados Intensivos a nivel nacional. Los pacientes se clasificaron según las patologías: sepsis, cardiovascular, respiratorias, neurológicas, trauma, digestivos, renales y otros. Resultados: Las patologías que presentan mayor mediana de costos por día cama son: sepsis ($362.115), respiratorias ($352.793), trauma ($348.442), renales ($341.928) y cardiovascular ($291.061). La estructura de costos del día cama está conformada principalmente por el costo asociado al recurso humano, cuyo valor máximo asciende a 64 por ciento, seguido del costo asociado a los medicamentos con un valor máximo de 15 por ciento. Los pacientes con sepsis y trauma absorben la mayor proporción de recursos en la Unidad de Cuidados Intensivos en estudio; 35 por ciento y 19 por ciento respectivamente y una proporción significativa de dichos costos es utilizada por pacientes que fallecen (34 por ciento y 19 por ciento) respectivamente. Conclusión: Todas las patologías en estudio tienen desviación desfavorable de costos, con respecto al arancel fijado por Fonasa, que sólo asciende a $192.160, para el año 2011.
The aim of the study is measures the real costs associated with the pathologies treated in the of Intensive Care Unid (ICU) Adults of the Public Hospitals of the region of the Maule, and to compare them with the cost assigned by Fonasa to the bed/day for the year 2011. Materials and methods: it is a question of a market study, applying the Activity-based costing (ABC). There was included 469 patients, 222 patients of the ICU of the Curicós Hospital and 247 patients the ICU of the Talcas Hospital between January 01 and August 30, 2011, which in agreement to age and APACHE II, represent the levels of patients complexity of ICU to national level. The patients qualified according to the pathologies: sepsis, cardiovascular, respiratory, neurological, trauma, digestive, renal and others. Results: The pathologies that present major median of costs per day bed are: sepsis ($362.115), respiratory ($352.793),trauma ($348.442), renal ($341.928) and cardiovascular ($291.061). The structure of costs of the day bed is shaped principally by the cost associated with the human resource, which maximum value promotes 64 percent, followed by the cost associated with the medicines with a maximum value of 15 percent. The patients with sepsis and trauma absorbed the major proportion of resources in the ICU in our study; 35 percent and 19 percent respectively and a significant proportion of the abovementioned costs is used by patients who die (34 percent and 19 percent)respectively. Conclusion: All the pathologies in study have unfavorable diversion of costs, with regard to the duty fixed by Fonasa, which only promotes to $192.160, for the year2011.