Quick and Simple Detection Technique to Assess the Binding of Antimicrotubule Agents to the Colchicine-Binding Site

Development of antimitotic binding to the colchicine-binding site for the treatment of cancer is rapidly expanding. Numerous antimicrotubule agents are prepared every year, and the determination of their binding affinity to tubulin requires the use of purified tubulins and radiolabeled ligands. Such a procedure is costly and time-consuming and therefore is limited to the most promising candidates. Here, we report a quick and inexpensive method that requires only usual laboratory resources to assess the binding of antimicrotubules to colchicine-binding site. The method is based on the ability of N,N'-ethylene-bis(iodoacetamide) (EBI) to crosslink in living cells the cysteine residues at position 239 and 354 of β-tubulin, residues which are involved in the colchicine-binding site. The β-tubulin adduct formed by EBI is easily detectable by Western blot as a second immunoreacting band of β-tubulin that migrates faster than β-tubulin. The occupancy of colchicine-binding site by pertinent antimitotics inhibits the formation of the EBI: β-tubulin adduct, resulting in an assay that allows the screening of new molecules targeting this binding site

Economía circular del conocimiento

Este Trabajo de Fin Máster está desarrollado considerando una aproximación teórico-conceptual donde se analiza, argumenta y reflexiona sobre la práctica de la actividad docente desde un punto de vista empírico y pragmático. Luego se realiza una aproximación práctica diseñando una concreción de esta teoría mediante la elaboración de una unidad didáctica para la asignatura de Tecnología de 2º de la ESO. “Economía circular del conocimiento” es el nombre elegido para esta teoría conceptual, fundamentada básicamente en el intercambio de roles docente/alumno en el proceso de enseñanza-aprendizaje, y en el aprovechamiento eficiente de los variados e innumerables recursos intangibles que poseen alumnos y docentes. Algunos elementos en los que nos basamos para elaborar esta teoría son, por ejemplo, metodologías de enseñanza tales como tutoría entre iguales, aprender enseñando, aprender para enseñar, aprendizaje cooperativo y colaborativo, etc.; y conceptos pedagógicos contrastados como: aprender a aprender, aprendizaje significativo, aprendizaje a lo largo de la vida, aprendizaje centrado en el alumno, etc. “Aprendiendo Google Classroom” es la unidad didáctica diseñada basada en algunos de los principios metodológicos y conceptos pedagógicos citados previamente, y que intenta ejemplificar como podemos apoyarnos en la teoría de “Economía circular de conocimiento” al momento de realizar una intervención educativa.<br /

Characterization of rice husk-based catalyst prepared via conventional and microwave carbonisation

© 2017 Elsevier Ltd. Carbon-based sulphonated catalysts (CBSCs) were made from rice husk for biodiesel production. The CBSCs were prepared by microwave (MW) and conventional heating processes from the same feedstock. In both heating systems, the preparation was a two-step process: carbonisation and sulphonation. The aim of this study was to use MW heating to reduce the conventional CBSC preparation time and enhance the -SO 3 H group attachment to the solid catalyst. The biomass based solid acid catalysts from the two systems were characterised and compared in terms of physicochemical properties including: sulphonation, morphology, surface area and structure. The reaction times for MW assisted carbonisation and for sulphonation were significantly reduced compared to the conventional heating system; these were 30 min vs 4 h and 20 min vs 12 h, respectively. The MW prepared catalyst showed higher sulphur content (4.91%) as compared to the conventional catalyst (2.10%). The FTIR analysis showed well distinguished peaks for -SO 3 H for the MW prepared catalyst suggesting the solid catalyst was successfully sulphonated, while these peaks were very weak for the conventional catalyst. SEM analysis revealed a highly porous structure in the MW prepared catalyst, whilst a denser solid resulted for its conventionally prepared analogue, owing to the higher temperatures applied and longer sulphonation time. The surface area for the MW was higher than the conventionally prepared catalysts (43.63 m 2 /g and 37.01 m 2 /g, respectively). The structure of the samples was identified as amorphous for both catalysts as confirmed by XRD. The prepared CBSC is expected to catalyse biodiesel production reaction as evidenced by its total acidity and surface area

Quantitative analysis of the effect of tubulin isotype expression on sensitivity of cancer cell lines to a set of novel colchicine derivatives

<p>Abstract</p> <p>Background</p> <p>A maximum entropy approach is proposed to predict the cytotoxic effects of a panel of colchicine derivatives in several human cancer cell lines. Data was obtained from cytotoxicity assays performed with 21 drug molecules from the same family of colchicine compounds and correlate these results with independent tubulin isoform expression measurements for several cancer cell lines. The maximum entropy method is then used in conjunction with computed relative binding energy values for each of the drug molecules against tubulin isotypes to which these compounds bind with different affinities.</p> <p>Results</p> <p>We have found by using our analysis that <it>αβ</it>I and <it>αβ</it>III tubulin isoforms are the most important isoforms in establishing predictive response of cancer cell sensitivity to colchicine derivatives. However, since <it>αβ</it>I tubulin is widely distributed in the human body, targeting it would lead to severe adverse side effects. Consequently, we have identified tubulin isotype <it>αβ</it>III as the most important molecular target for inhibition of microtubule polymerization and hence cancer cell cytotoxicity. Tubulin isotypes <it>αβ</it>I and <it>αβ</it>II are concluded to be secondary targets.</p> <p>Conclusions</p> <p>The benefit of being able to correlate expression levels of specific tubulin isotypes and the resultant cell death effect is that it will enable us to better understand the origin of drug resistance and hence design optimal structures for the elimination of cancer cells. The conclusion of the study described herein identifies tubulin isotype <it>αβ</it>III as a target for optimized chemotherapy drug design.</p

Ab-Initio Molecular Dynamics

Computer simulation methods, such as Monte Carlo or Molecular Dynamics, are very powerful computational techniques that provide detailed and essentially exact information on classical many-body problems. With the advent of ab-initio molecular dynamics, where the forces are computed on-the-fly by accurate electronic structure calculations, the scope of either method has been greatly extended. This new approach, which unifies Newton's and Schr\"odinger's equations, allows for complex simulations without relying on any adjustable parameter. This review is intended to outline the basic principles as well as a survey of the field. Beginning with the derivation of Born-Oppenheimer molecular dynamics, the Car-Parrinello method and the recently devised efficient and accurate Car-Parrinello-like approach to Born-Oppenheimer molecular dynamics, which unifies best of both schemes are discussed. The predictive power of this novel second-generation Car-Parrinello approach is demonstrated by a series of applications ranging from liquid metals, to semiconductors and water. This development allows for ab-initio molecular dynamics simulations on much larger length and time scales than previously thought feasible.Comment: 13 pages, 3 figure

Situacion tecnico productiva y socioeconomica de los pequenos productores vitivinicolas del secano interior en la VII Region: propuesta de soluciones

Resumen (Spanish, English)115 p.Durante años el sector vitivinícola tradicional de la zona de secano interior es sinónimo de una viticultura pobre y en decadencia, muchos estudios de organismos gubernamentales y no gubernamentales en el transcurso de los últimos años han buscado diversas fórmulas y alternativas de reconversión productiva para este sector, sin embargo pocos han sido orientados hacia la capacidad real de adoptar estas nuevas propuestas tomando en consideración aspectos económicos, sociales y perceptivos por parte del pequeño productor. En el presente trabajo se realizó una evaluación económica de dos alternativas de producción para la zona de secano interior distintas a la alternativa productiva tradicional, se utilizaron los parámetros de evaluación del VAN (Valor Actual Neto) y TIR (Tasa interna de Retorno), en donde utilizando como material de apoyo una encuesta realizada a 90 productores de la Comuna de Cauquenes, se estructura un análisis que además de considerar aspectos técnico - económicos, evidencia aspectos sociales y de percepción trascendentales para la puesta en marcha de cualquier intento de reordenamiento productivo. Dicho estudio evidenció el hecho que ante cualquier intento de establecer nuevas alternativas productivas para la zona, se deben considerar aspectos que van mucho mas allá de la factibilidad técnica de dicha alternativa, aspectos como el tradicionalismo establecido, la desconfianza generalizada, la reducida capacidad crediticia, y la falta de oportunidades que enfrentan en su condición de productores tradicionales