The molecular binding interactions of inhibitors and activators of phosphoenolpyruvate carboxylase

We have performed molecular modelling studies of the binding to maize phosphoenolpyruvate carboxylase (PEPC) of phosphoenolpyruvate (PEP) and a number of representative competitive inhibitors. We predict that all these compounds share a common binding mode and that the differences in inhibitory activity of the various inhibitors arise mainly from either increased hydrophobic interactions of cis substituents or small but significant changes in their binding mode arising from steric clashes of trans substituents with the active site. We have also performed molecular modelling studies of glucose-6-phosphate (G6P) and a number of other allosteric activators in their putative allosteric binding site in this enzyme. We predict that these molecules share the same binding mode for their phosphate moiety while some of them engage in a variety of hydrogen bonding interactions with residues from different subunits of the enzyme, and others establish hydrophobic and van der Waals interactions with other regions of the allosteric binding site

The emerging application of ultrasound in lactose crystallisation

Ultrasonic processing is the industrial application of sound waves with a frequency above the upper limit of human hearing. Interest has arisen recently in the effects of ultrasound on the crystallisation of lactose as an innovative technology to improve its recovery and the control over its crystal properties. This not only will increase the financial profit for lactose manufacturers and improve the quality of lactose for specific applications, but will also improve the quality of end products manufactured with lactose as an ingredient

Molecular dynamics simulations of mixed DOPC–β-sitosterol bilayers and their interactions with DMSO

ell membrane phospholipid bilayers can be damaged by the large amounts of dimethyl sulphoxide (DMSO) commonly used in cryopreservation. The interaction of DMSO with model bilayers consisting of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and ß-sitosterol has been studied using molecular dynamics simulations. Initially the effect of sterol concentration and temperature upon bilayers solvated in pure water was determined, and membranes containing ß-sitosterol were compared with membranes containing cholesterol. These simulations showed that the presence of sterols has a condensing effect on the phospholipids, causing a reduction in the area per lipid as the sterol concentration increases, up to a phospholipid–sterol ratio of 2[thin space (1/6-em)]:[thin space (1/6-em)]1. The incorporation of sterols into the bilayer also increased the thickness and order of the phospholipid acyl tails. DOPC–ß-sitosterol bilayers at different relative concentrations were simulated in solutions of 2.5 and 25.0 mol% DMSO. The interaction of DMSO with the bilayers caused the bilayers to expand laterally, while thinning normal to the plane of the bilayer expansion. The same qualitative behaviour has been shown to occur in pure phosphocholine bilayers. However, the presence of sterols made the membranes more resistant to the effects of DMSO, to the extent that the membranes where able to maintain their integrity in 25.0 mol% DMSO, a concentration that would otherwise cause the destruction of a pure DOPC bilayer. Increasing the concentration of ß-sitosterol within the bilayers reduced the rate of DMSO diffusion across the bilayer and, if the concentration was large enough, caused the diffusion mechanism to change. DMSO was observed to disorder the membranes enough to cause an increase in the number of sterol “flip–flops”. The findings of this work provide a more realistic description of how DMSO interacts with cell membranes and the role of the composition of the membrane

Electrochemistry of proteins at the interface between two immiscible electrolyte solutions

The electrochemistry of proteins at the interface between two immiscible electrolyte solutions (ITIES) is discussed, with detection capabilities based on protein-facilitated anion transfer, and which has enabled protein detection via adsorptive stripping voltammetry. Targeting an enzymatic biomarker has achieved detection at picomolar concentrations, whilst studies into structural aspects of proteins at the ITIES have revealed formation of oligomers (cytochrome c) and unfolded protein (lysozyme) together with alterations to the protein secondary structures

Molecular dynamics simulation of the phosphorylation-induced conformational changes of a tau peptide fragment

Aggregation of the microtubule associated protein tau (MAPT) within neurons of the brain is the leading cause of tauopathies such as Alzheimer's disease. MAPT is a phospho-protein that is selectively phosphorylated by a number of kinases in vivo to perform its biological function. However, it may become pathogenically hyperphosphorylated, causing aggregation into paired helical filaments and neurofibrillary tangles. The phosphorylation induced conformational change on a peptide of MAPT (htau225-250) was investigated by performing molecular dynamics simulations with different phosphorylation patterns of the peptide (pThr231 and/or pSer235) in different simulation conditions to determine the effect of ionic strength and phosphate charge. All phosphorylation patterns were found to disrupt a nascent terminal ß-sheet pattern (226VAVVR230 and 244QTAPVP249), replacing it with a range of structures. The double pThr231/pSer235 phosphorylation pattern at experimental ionic strength resulted in the best agreement with NMR structural characterization, with the observation of a transient α-helix (239AKSRLQT245). PPII helical conformations were only found sporadically throughout the simulations

The Biological and Biophysical Properties of the Spider Peptide Gomesin

This review summarises the current knowledge of Gomesin (Gm), an 18-residue long, cationic anti-microbial peptide originally isolated from the haemocytes of the Brazilian tarantula Acanthoscurria gomesiana. The peptide shows potent cytotoxic activity against clinically relevant microbes including Gram-positive and Gram-negative bacteria, fungi, and parasites. In addition, Gm shows in-vitro and in-vivo anti-cancer activities against several human and murine cancers. The peptide exerts its cytotoxic activity by permeabilising cell membranes, but the underlying molecular mechanism of action is still unclear. Due to its potential as a therapeutic agent, the structure and membrane-binding properties, as well as the leakage and cytotoxic activities of Gm have been studied using a range of techniques. This review provides a summary of these studies, with a particular focus on biophysical characterisation studies of peptide variants that have attempted to establish a structure-activity relationship. Future studies are still needed to rationalise the binding affinity and cell-type-specific selectivity of Gm and its variants, while more pre-clinical studies are required to develop Gm into a therapeutically useful peptide

Kinetics of the crystallisation of Ni-Zn ferrite powders prepared by the hydrothermal method

Recently published data on the precipitation of Ni-Zn ferrite powders prepared by the hydrothermal method have been analysed in a manner consistent with Avrami theory. The results indicate that the value of the time exponent is due to the growth of spherical particles in a solution which becomes progressively depleted of reactants. The analysis also indicates that the process can be considered to be one in which the particles all start growth from the initiation of the reaction

Evaluación de imágenes de radar Sentinel- 1A e imágenes multiespectrales Sentinel-2A en la clasificación de cobertura del suelo en diferentes niveles de detalle

En este proyecto se evaluó el potencial de imágenes capturadas por Sentinel-1A y Sentinel-2A para la generación de cartografía temática de cobertura del suelo en tres niveles de detalle: exploratorio, de reconocimiento y semi-detallado, usando el sistema de clasificación CLCc (Corine Land Cover adaptado para Colombia). Para el efecto, se aplicaron y compararon dos técnicas de clasificación digital de imágenes: (i) basado en pixeles y (ii) orientado a objetos. En los dos casos se usó el algoritmo de aprendizaje automático denominado RandomForest. . La clasificación se realizó en dos zonas de estudio con diferente relieve: una de baja pendiente y otra de alta pendiente. El proyecto permitió identificar los canales de radar Sentinel-1A, las bandas Sentinel-2A y los índices multiespectrales relevantes en la categorización de coberturas. Igualmente se evaluó la exactitud temática mediante matrices de confusión, validación cruzada e índice Kappa usando como referencia los resultados de interpretación visual de las imágenes Sentinel-2A. Se encontró que las variables que aportan mayor información para la discriminación de coberturas son Banda 2 – Banda 3 – Banda 5 – Banda 8A - EVI Banda 5 – EVI Banda 8A de Sentinel-1A y los índices de radar (VH – VV-VH – (VV-VH)/2 de Sentinel-2A. Se comprobó que los valores de exactitud temática disminuyen a medida que el nivel de detalle y el número de clases de interés aumentan. Igualmente, se encontró que las clases que presentaron la mejor exactitud fueron territorios agrícolas para nivel 1, pastos para nivel 2 y pastos limpios para nivel 3. Los resultados obtenidos sugieren que la integración de datos multiespectrales y datos de radar mejora las clasificaciones que se basan en una sola fuente de datos. Igualmente, que la exactitud temática en zonas de baja pendiente es más alta que la obtenida en zonas de alta pendiente. En síntesis, se puede afirmar que las imágenes analizadas tienen un gran potencial para la clasificación de cobertura en diferentes niveles de detalle.Abstract: In this project, the potential of Sentinel-1A and Sentinel-2A images is evaluated for the generation of thematic cartography of soil cover in three levels of detail: that is, exploratory, recognition and semi-detailed, using the Corine Land Cover classification system adapted for Colombia for this, it was applied and compared techniques of image classification: (i) based on pixels; and (ii) object oriented. In both cases the automatic learning algorithm called RandomForest was used. The classification was carried out in two study areas with different aspects. The project allowed the identification of radar channels Sentinel-1A, bands of Sentinel-2A and multispectral indexes are relevant for the categorization of coverage. Likewise, the thematic accuracy was assessed using confusion matrices, cross validation and index. Kappa based on land use obtained by visual interpretation of the Sentinel-2A was found that the bands that provide discriminative information about cover are Band 2 - Band 3 - Band 5 - Band 5 A - EVI Band 5 - EVI Band 8A of Sentinel-1A, and radar indices (VH - VV - VH - (VV - VH) / 2 of Sentinel-2A. It was show that thematic accuracy decrease as the level of detail and the number of interest classes- increase. Also, we find that the classes that present the best results for level 1, pastures for level 2 and pastures clean for level 3. The results multispectral and radar data provide better results than using a single source. The thematic precision in the areas of low slope is higher than the correct one in the zones of high slope. In summary, it can be affirmed that the analyzed images have a great potential for the classification of coverage in different levels of detail.Maestrí

Nobles de papel: a la búsqueda de una identidad perdida

Reseña del libro Nobles de papel. Identidades oscilantes y genealogías borrosas en los descendientes de la realeza inca, de Rocío Quispe Agnoli, Iberoamericana-Vervuert, 2016

El americanismo de Rafael Altamira como puente de una revolución intelectual

This article explores the contributions from Alicante’s historian Rafael Altamira y Crevea, who in 1909 was appointed by the University of Oviedo, institution in which he was a professor, to travel to various educational institutions in Argentina, Chile, Mexico, Peru, Cuba, Uruguay and the United States with the definite intention of establishing academic and intellectual relationships between America and Spain. The transcendence of this visit is stressed, as the intellectual’s ideas were well received by the public opinion as well as the implementation of mechanisms for the interchange of human and material resources between both continents and their influence in the construction of the project of the National Autonomous University of  Mexico.Este artículo explora los aportes del historiador alicantino Rafael Altamira y Crevea, quien en 1909 fue comisionado por la Universidad de Oviedo, institución en la que era catedrático, para realizar un viaje por  instituciones educativas de Argentina, Chile, México, Perú, Cuba, Uruguay y Estados Unidos con el claro objetivo de restablecer las relaciones académicas e intelectuales entre América y España. Se hace hincapiéen la trascendencia de esta visita, que se reflejó en la buena aceptación de las ideas del intelectual por parte de la opinión pública, la implementación de mecanismos para el intercambio de recursos humanos y materiales entre ambos continentes y su influencia en la construcción del proyecto de la Universidad Nacional de México