A yeast three-hybrid system that reconstitutes mammalian hypoxia inducible factor regulatory machinery

Background: Several human pathologies, including neoplasia and ischemic cardiovascular diseases, course with an unbalance between oxygen supply and demand ( hypoxia). Cells within hypoxic regions respond with the induction of a specific genetic program, under the control of the Hypoxia Inducible Factor (HIF), that mediates their adaptation to the lack of oxygen. The activity of HIF is mainly regulated by the EGL-nine homolog (EGLN) enzymes that hydroxylate the alpha subunit of this transcription factor in an oxygen-dependent reaction. Hydroxylated HIF is then recognized and ubiquitinilated by the product of the tumor suppressor gene, pVHL, leading to its proteosomal degradation. Under hypoxia, the hydroxylation of HIF by the EGLNs is compromised due to the lack of oxygen, which is a reaction cosubstrate. Thus, HIF escapes degradation and drives the transcription of its target genes. Since the progression of the aforementioned pathologies might be influenced by activation of HIF-target genes, development of small molecules with the ability to interfere with the HIF-regulatory machinery is of great interest.Results: Herein we describe a yeast three-hybrid system that reconstitutes mammalian HIF regulation by the EGLNs and VHL. In this system, yeast growth, under specific nutrient restrictions, is driven by the interaction between the beta domain of VHL and a hydroxyproline-containing HIF alpha peptide. In turn, this interaction is strictly dependent on EGLN activity that hydroxylates the HIFa peptide. Importantly, this system accurately preserves the specificity of the hydroxylation reaction toward specific substrates. We propose that this system, in combination with a matched control, can be used as a simple and inexpensive assay to identify molecules that specifically modulate EGLN activity. As a proof of principle we show that two known EGLN inhibitors, dimethyloxaloylglycine (DMOG) and 6-chlor-3-hydroxychinolin-2-carbonic acid-N-carboxymethylamide (S956711), have a profound and specific effect on the yeast HIF/EGLN/VHL system.Conclusion: The system described in this work accurately reconstitutes HIF regulation while preserving EGLN substrate specificity. Thus, it is a valuable tool to study HIF regulation, and particularly EGLN biochemistry, in a cellular context. In addition, we demonstrate that this system can be used to identify specific inhibitors of the EGLN enzymes

Blockchain Technology Facing Socioeconomic Challenges. Promise versus Probability

This paper has the main purpose to make a critical and balanced analysis about the potential of blockchain technology to face some of the great current socioeconomic challenges, being focus on impact assessment point of view, analyzing the disruptive potential of blockchain to provide solutions at level of different challenges as example, climate change, migrant movements, gender equality, financial inclusion or the cost opportunity of the management of data science

La formación universitaria del profesorado de enseñanza secundaria ante el reto del proceso de convergencia europea

La formación inicial del profesorado de enseñanza secundaria en España se basa en un modelo que tuvo su origen en un contexto educativo y social distinto al actual y presenta numerosas deficiencias ya que, entre otras cosas, no proporciona a los futuros profesores los instrumentos psicopedagógicos y didácticos adecuados para enfrentarse a los retos de la nueva educación secundaria. En este trabajo presentamos un análisis crítico y una revisión histórica de los distintos marcos normativos que han regulado la formación docente inicial en nuestro país, durante las últimas décadas, con objeto de formular algunas propuestas de mejora de la situación actual, relacionadas con el proceso de convergencia hacia el Espacio Europeo de Educación Superior

Nature-inspired synthesis of rational protocols

Proceedings of: 10th International Conference on Parallel Problem Solving from Nature (PPSN 2008), Dortmund, Germany, September 13-17, 2008.Rational cryptography is an emerging field which combines aspects traditionally related to security with concepts described in economic theoretical frameworks. For example, it applies game theory concepts to address security problems arising when executing cryptographic protocols. The aim is to replace the assumption of a worst-case attacker by the notion of rational agents that try to maximize their payoffs. In this work, we define a formal framework and a meta--heuristic technique for the automated synthesis of multi-party rational exchange security (M-RES) protocols. We provide experimental results for a simple scenario where a 3-party rational exchange protocol is automatically designed.Publicad

Migración intrapélvica (cut-in) en un clavo Gamma. Caso Clínico

Una de las complicaciones de los clavos intramedulares es sin duda la implantación central del tornillo cérvico-cefálico. Aún así, la confluencia de diversos factores (osteoporosis, trazo de la fractura, reducción insuficiente del foco, motorización reiterada, etc.) pueden precipitar la salida de éste (cut-out) que viene a evidenciar una prevalencia del 2 al 4% de las diversas series y, ulterior aflojamiento del montaje. La presencia del cut-in, supone una eventualidad muy ocasional por debajo del 0,3% de la literatura. En este caso se ilustra una consolidación definitiva afortunada, tras un abanico de factores mecánicos y estructurales que encaminaron a una doble cirugía terapéutica. Se analizan los factores biomecánicos implicados en la génesis del cut-in.One common complication of intramedullary nails is the central implantation of the cervico-cephalic screw. However, the confluence of some factors (osteoporosis, fracture line, inadequate focus reduction, repeated motorizing, etc.) can hasten a cut-out, showing a prevalence of 2 to 4% of the diverse series, and further assembly loosening. The presence of cut-in is an infrequent eventuality under the 0.3% of literature. The present case illustrates a fortunate definite consolidation, after a range of mechanical an structural factors leading to a double therapeutic surgery. The biomechanical factors affecting the cut-in origin are analysed.Peer Reviewe

The mediterranean biotypes of Tylenchulus semipenetrans in Spanish citrus orchards

Les capacités de reproduction de quatorze populations du nématode des citrus (#Tylenchulus semipenetrans$) collectées dans la principale zone de citriculture de l'Espagne ont été comparées sur oranger amer et citrange Carrizo. Toutes les populations ont été identifiées comme appartenant au biotype méditerranéen. La capacité de reproduction varie considérablement en fonction des populations. Le pouvoir infestant et le taux de reproduction des populations collectées dans la rhizosphère des porte-greffes citranges Troyer ou Carrizo sont plus élevés (P supérieur ou égal à 0,05) que ceux des populations collectées sur oranger amer. (Résumé d'auteur

Modificaciones técnicas en fermentadores de flujo continuo: efectos sobre la población de protozoos y la fermentación

Los sistemas in vitro de simulación de la fermentación ruminal constituyen herramientas muy útiles para el estudio de la función ruminal. El mantenimiento de poblaciones microbianas representativas de las existentes en el rumen de los animales es uno de los requisitos que deberían cumplir los sistemas in vitro, pero la disminución del número de protozoos en los fermentadores es un hecho bien constatado (Moumen et al., 2009; Martínez et al., 2011). Dado el importante papel que los protozoos desempeñan en la función ruminal, el diseño de modificaciones técnicas que permitan mantener estas poblaciones en fermentadores supondría un importante avance para su utilización en el estudio del ecosistema ruminal. El objetivo del presente trabajo fue analizar dos modificaciones técnicas para mejorar la retención de los protozoos en fermentadores de flujo continuo