Components of Intraflagellar Transport Complex A Function Independently of the Cilium to Regulate Canonical Wnt Signaling in Drosophila.

The development of multicellular organisms requires the precisely coordinated regulation of an evolutionarily conserved group of signaling pathways. Temporal and spatial control of these signaling cascades is achieved through networks of regulatory proteins, segregation of pathway components in specific subcellular compartments, or both. In vertebrates, dysregulation of primary cilia function has been strongly linked to developmental signaling defects, yet it remains unclear whether cilia sequester pathway components to regulate their activation or cilia-associated proteins directly modulate developmental signaling events. To elucidate this question, we conducted an RNAi-based screen in Drosophila non-ciliated cells to test for cilium-independent loss-of-function phenotypes of ciliary proteins in developmental signaling pathways. Our results show no effect on Hedgehog signaling. In contrast, our screen identified several cilia-associated proteins as functioning in canonical Wnt signaling. Further characterization of specific components of Intraflagellar Transport complex A uncovered a cilia-independent function in potentiating Wnt signals by promoting ß-catenin/Armadillo activity.

Biomarcadores en los síndromes coronarios agudos con y sin elevación del ST / Biomarkers in acute coronary syndromes with and without ST elevation

Introducción y objetivos. En el síndrome coronario agudo se produce un fenómeno inflamatorio con alteración de diversos marcadores analíticos. Su conocimiento podría ayudarnos a estratificar mejor el riesgo y a elegir el tratamiento más adecuado. Métodos. Se estudió a 151 pacientes consecutivos ingresados con síndrome coronario agudo sin elevación del ST (SCASEST) y síndrome coronario agudo con elevación del ST (SCACEST). Se determinaron los factores de riesgo cardiovascular clásicos (diabetes mellitus, hipertensión arterial, hipercolesterolemia, antecedentes familiares y personales de cardiopatía isquémica y tabaquismo) y diversos marcadores analíticos entre los que se incluyeron la insulinemia, el fibrinógeno, la proteína C reactiva, la lipoproteína (a) y la velocidad de sedimentación globular. Resultados. Del total de pacientes, 88 (58,3%) presentaron SCASEST y 63 (41,7%), SCACEST. Los pacientes con SCASEST tuvieron de forma significativa una incidencia mayor de diabetes mellitus y de antecedentes personales de cardiopatía isquémica que los que presentaron SCACEST. En los pacientes con SCACEST se obtuvieron de forma significativa cifras más elevadas de fibrinógeno, proteína C reactiva, transaminasa glutamicoxalacética y transaminasa glutámico pirúvica. El análisis multivariante mostró que la diabetes mellitus y los antecedentes personales eran más frecuentes en pacientes con SCASEST, mientras que los valores de fibrinógeno eran más elevados en pacientes con SCACEST. Conclusiones. Los pacientes diabéticos y con antecedentes personales de cardiopatía isquémica presentaron SCASEST de forma más frecuente. De los parámetros estudiados, el fibrinógeno se encontró de forma significativa más elevado en los pacientes con SCACEST (AU)

Introduction and objectives. Acute coronary syndrome involves an inflammatory process which has several analytical markers. Knowledge of those could help us improve the risk classification and choose the most appropriate treatment. Methods. A total of 151 consecutive patients with STE-ACS and NSTE-ACS (ST elevated and non-ST elevated acute coronary syndrome) were studied. The classic cardiovascular risk factors (diabetes mellitus, high blood pressure, family and personal history and smoking habits) were determined along with several analytical markers, among which were included insulin, fibrinogen, C-reactive protein, Lp(a) and erythrocyte sedimentation rate. Results. Of the total pateints, 88 (58.3%) had NSTE-ACS and 63 (41.7%) with STE-ACS . Patients with NSTE-ACS had a significantly higher incidence of diabetes mellitus and personal history of ischaemic heart disease than those who had a STE-ACS. Significantly higher levels of fibrinogen, C-reactive protein, GoT and GPT were obtained in patients with STE-ACS. The multivariate analysis showed that diabetes mellitus and a personal history were more frequent in NSTE-ACS, while fibrinogen levels were higher in those who had STE-ACS. Conclusions. NSTE-ACS is more frequent in patients with diabetes and those with a personal history of ischaemic heart disease. Of the parameters studied, fibrinogen was found to be significantly higher in patients with STE-ACS (AU)

Lines is required for normal operation of Wingless, Hedgehog and Notch pathways during wing development.

The regulatory Lines/Drumstick/Bowl gene network is implicated in the integration of patterning information at several stages during development. Here, we show that during Drosophila wing development, Lines prevents Bowl accumulation in the wing primordium, confining its expression to the peripodial epithelium. In cells that lack lines or over-expressing Drumstick, Bowl stabilization is responsible for alterations such as dramatic overgrowths and cell identity changes in the proximodistal patterning owing to aberrant responses to signaling pathways. The complex phenotypes are explained by Bowl repressing the Wingless pathway, the earliest effect seen. In addition, Bowl sequesters the general co-repressor Groucho from repressor complexes functioning in the Notch pathway and in Hedgehog expression, leading to ectopic activity of their targets. Supporting this model, elimination of the Groucho interaction domain in Bowl prevents the activation of the Notch and Hedgehog pathways, although not the repression of the Wingless pathway. Similarly, the effects of ectopic Bowl are partially rescued by co-expression of either Hairless or Master of thickveins, co-repressors that act with Groucho in the Notch and Hedgehog pathways, respectively. We conclude that by preventing Bowl accumulation in the wing, primordial Lines permits the correct balance of nuclear co-repressors that control the activity of the Wingless, Notch and Hedgehog pathways.