Nitric Oxide Destabilizes Pias3 and Regulates Sumoylation

Small ubiquitin-related protein modifiers (SUMO) modification is an important mechanism for posttranslational regulation of protein function. However, it is largely unknown how the sumoylation pathway is regulated. Here, we report that nitric oxide (NO) causes global hyposumoylation in mammalian cells. Both SUMO E2 conjugating enzyme Ubc9 and E3 ligase protein inhibitor of activated STAT3 (Pias3) were targets for S-nitrosation. S-nitrosation did not interfere with the SUMO conjugating activity of Ubc9, but promoted Pias3 degradation by facilitating its interaction with tripartite motif-containing 32 (Trim32), a ubiquitin E3 ligase. On the one hand, NO promoted Trim32-mediated Pias3 ubiquitination. On the other hand, NO enhanced the stimulatory effect of Pias3 on Trim32 autoubiquitination. The residue Cys459 of Pias3 was identified as a target site for S-nitrosation. Mutation of Cys459 abolished the stimulatory effect of NO on the Pias3-Trim32 interaction, indicating a requirement of S-nitrosation at Cys459 for positive regulation of the Pias3-Trim32 interplay. This study reveals a novel crosstalk between S-nitrosation, ubiquitination, and sumoylation, which may be crucial for NO-related physiological and pathological processes

Is family medicine responsive to current health problems and people’s needs?

Family medicine in Chile was initially introduced in the early eighties. From then on, roughly 500 family doctors have been trained in seven universities. The Chilean Family Medicine Society was founded in the early nineties and became a reference point for family doctors, thus setting the stage to position family medicine in the broader national context. Just like in other countries, this has been a arduous task

Dépression post-natale : évaluation d'un outil de dépistage l'Edinburgh Postnatal Depression Scale

Notre étude s’est intéressée à l’insuffisance de dépistage de la dépression post-natale (DPN), problème de santé publique actuel, puisque cette pathologie est trop souvent banalisée, sous-diagnostiquée et donc non traitée. En s’appuyant sur une revue de la littérature, nous avons décidé de réaliser une évaluation de l’Edinburgh Postnatal Depression Scale (EPDS), outil de dépistage validé de la dépression post-natale, utilisé de façon systématique par les sages-femmes durant la visite post-natale. Notre méthodologie était basée sur trois phases : l’évaluation des connaissances des sages-femmes au sujet de la DPN et de son dépistage, l’utilisation par ces sages-femmes de l’EPDS et enfin l’évaluation de l’outil. 18 sages-femmes de Haute-Normandie se sont prêtées à l’exercice et nous ont permis d’aboutir aux résultats suivants : les connaissances au sujet de la dépression post-natale sont parfois insuffisantes, quant à l’EPDS il n’est que trop peu connu par les sages-femmes, pourtant notre enquête a démontré que 15 des professionnels interrogés ont manifesté la volonté de le réutiliser, car il a été jugé efficace et utile pour aborder le sujet de la DPN avec les patientes qui l’ont plutôt bien accepté. Véritable réflexion autour de la DPN, les résultats de cette étude démontrent que pour une meilleure prise en charge des patientes confrontées à cette pathologie, l’ensemble des professionnels de la périnatalité doivent être sensibilisés à son dépistage notamment grâce à l’utilisation de l’EPDS

¿Qué se espera de los docentes en la Innovación Curricular?

This article first rewiews the basis and principles that support curriculum innovation. Keeping this in mind, the role teachers must play in this process, becomes clear almost spontaneously

Régulation des complexes d'ubiquitinylation et de sumoylation par la ligase E3 hSIAH2

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Dimerization of hSiah proteins regulates their stability

International audienc

The death-associated protein DAXX is a novel histone chaperone involved in the replication-independent deposition of H3.3

The histone variant H3.3 marks active chromatin by replacing the conventional histone H3.1. In this study, we investigate the detailed mechanism of H3.3 replication-independent deposition. We found that the death domain-associated protein DAXX and the chromatin remodeling factor ATRX (α-thalassemia/mental retardation syndrome protein) are specifically associated with the H3.3 deposition machinery. Bacterially expressed DAXX has a marked binding preference for H3.3 and assists the deposition of (H3.3–H4)2 tetramers on naked DNA, thus showing that DAXX is a H3.3 histone chaperone. In DAXX-depleted cells, a fraction of H3.3 was found associated with the replication-dependent machinery of deposition, suggesting that cells adapt to the depletion. The reintroduced DAXX in these cells colocalizes with H3.3 into the promyelocytic leukemia protein (PML) bodies. Moreover, DAXX associates with pericentric DNA repeats, and modulates the transcription from these repeats through assembly of H3.3 nucleosomes. These findings establish a new link between the PML bodies and the regulation of pericentric DNA repeat chromatin structure. Taken together, our data demonstrate that DAXX functions as a bona fide histone chaperone involved in the replication-independent deposition of H3.3

Metodología para la evaluación de la relación costo-efectividad en centros de atención primaria de Chile Methodology for evaluating cost-effectiveness in primary health care centers in Chile

OBJETIVO: Presentar una metodología para la evaluación de la relación costo-efectividad en centros de atención primaria de salud (APS) a partir del modelo de atención familiar promovido en Chile y evaluar los resultados de los dos primeros años de funcionamiento del primer centro piloto que funciona bajo este nuevo modelo de atención primaria. MÉTODOS. Se realizó un estudio de costo-efectividad, con una perspectiva social y un horizonte temporal de un año. Para comparar el centro intervenido (universitario) con el centro de control (municipal) se construyó el índice compuesto de calidad de los centros de salud familiar (ICCESFAM), que combina indicadores técnicos y la percepción de los usuarios de los centros en seis dimensiones: accesibilidad, continuidad de la atención médica, enfoque clínico preventivo y promocional, resolutividad, participación, y enfoque biopsicosocial y familiar. Para calcular los costos se tomó en cuenta el gasto en los centros, el ahorro producido al resto del sistema sanitario y el gasto de bolsillo de los pacientes. Se estimó la razón costo-efectividad incremental (RCEI) y se realizó un análisis de sensibilidad. RESULTADOS: El centro de salud universitario resultó 13,4% más caro (US$8,93 anuales adicionales por inscrito) y más efectivo (ICCESFAM 13,3$ 0,67 por cada punto porcentual adicional que aumenta el ICCESFAM. CONCLUSIONES: Según el modelo elaborado de evaluación de centros de APS, los centros que siguen el modelo de salud familiar chileno son más efectivos, tanto por sus indicadores técnicos como por la valoración de sus usuarios, que los centros de APS tradicionales.OBJECTIVE: Present a methodology for evaluating cost-effectiveness in primary health care centers (PHCs) in Chile based on the family health care model promoted in Chile and evaluate the results of the first two years of operation of the first pilot center to work under this new primary-care model. METHODS: A cost-effectiveness study with a social perspective and a one-year time frame was conducted. In order to compare the university health center in question with the control (a municipal health center), a Family Health Center Composite Quality Index (FHCCQI) was devised. It combines technical indicators and user perceptions of the health centers in six areas: access, continuity of medical care, a preventive and promotional clinical approach, problem-solving capability, participation, and a biopsychosocial and family approach. In order to calculate the costs, the centers' expenses, the savings realized in the rest of the health system, and patients' out-of-pocket expenditures were considered. The incremental cost-effectiveness ratio (ICR) was estimated and a sensitivity analysis was performed. RESULTS: The university health center was 13.4% more expensive (an additional US$8.93 per annum per enrollee) and was more effective (FHCCQI 13.3$ 0.67 for each additional percentage point of FHCCQI increase. CONCLUSIONS: According to the PHC evaluation model that was implemented, the centers that follow the Chilean family health care model are more effective than traditional PHC centers, as measured by both technical indicators and user ratings