Prediction of Protein Oxidation Sites

Although reactive oxygen species are best known as damag- ing agents linked to aerobic metabolism, it is now clear that they can also function as messengers in cellular signalling processes. Methionine, one of the two sulphur containing amino acids in proteins, is liable to be oxidized by a well-known reactive oxygen species: hydrogen perox- ide. The awareness that methionine oxidation may provide a mecha- nism to the modulation of a wide range of protein functions and cellular processes has recently encouraged proteomic approaches. However, these experimental studies are considerably time-consuming, labor-intensive and expensive, thus making the development of in silico methods for predicting methionine oxidation sites highly desirable. In the field of pro- tein phosphorylation, computational prediction of phosphorylation sites has emerged as a popular alternative approach. On the other hand, very few in-silico studies for methionine oxidation prediction exist in the lit- erature. In the current study we have addressed this issue by developing predictive models based on machine learning strategies and models— random forests, support vector machines, neural networks and flexible discriminant analysis—, aimed at accurate prediction of methionine oxi- dation sites.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Los átomos de azufre próximos a los anillos de residuos aromáticos son menos susceptibles de ser oxidados

El grupo tioéter de las metioninas confiere, a las proteínas portadoras, una alta vulnerabilidad a la oxidación. Sin embargo, no todos los residuos metionil de una proteína son igualmente susceptibles de oxidación. Aunque la accesibilidad del átomo de azufre al solvente es un factor importante, recientes experimentos ponen de manifiesto que dicho factor es insuficiente para explicar la amplia variabilidad en la reactividad que se observa. Así, pues, en el presente trabajo hemos explorado otros posibles determinantes estructurales que pudieran explicar dicha variabilidad. Para tal propósito, hemos empleado datos derivados de estudios de proteómica llevados a cabo con células humanas tratadas con H2O2. En el presente trabajo presentamos evidencias de que el entorno de aquellos residuos que aparecen oxidados, es claramente distinguible del entorno de aquellos otros residuos de metionina que no se oxidan bajo las mismas condiciones (p-valor = 10-23). El análisis de distancias interatómicas, llevado a cabo con más de un millar de átomos de azufre presentes en proteínas con estructuras conocidas, nos ha permitido desvelar un nuevo e importante determinante de la reactivadad frente a oxidantes. Aquellos átomos de azufre delta que interactúan con el anillo aromático de residuos fenilalanina, tirosina y triptófano, presentan una marcada resistencia a ser oxidados. En esta comunicación presentaremos evidencias de la menor reactividad de las metioninas que forman parte de motivos S-aromáticos tanto in vivo (estudios de proteoma redox) como in vitro (ensayos de oxidación química).Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Morphometric and microstructural characteristics of hippocampal subfields in mesial temporal lobe epilepsy and their correlates with mnemonic discrimination.

Pattern separation (PS) is a fundamental aspect of memory creation that defines the ability to transform similar memory representations into distinct ones, so they do not overlap when storing and retrieving them. Experimental evidence in animal models and the study of other human pathologies have demonstrated the role of the hippocampus in PS, in particular of the dentate gyrus (DG) and CA3. Patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HE) commonly report mnemonic deficits that have been associated with failures in PS. However, the link between these impairments and the integrity of the hippocampal subfields in these patients has not yet been determined. The aim of this work is to explore the association between the ability to perform mnemonic functions and the integrity of hippocampal CA1, CA3, and DG in patients with unilateral MTLE-HE. To reach this goal we evaluated the memory of patients with an improved object mnemonic similarity test. We then analyzed the hippocampal complex structural and microstructural integrity using diffusion weighted imaging. Our results indicate that patients with unilateral MTLE-HE present alterations in both volume and microstructural properties at the level of the hippocampal subfields DG, CA1, CA3, and the subiculum, that sometimes depend on the lateralization of their epileptic focus. However, none of the specific changes was found to be directly related to the performance of the patients in a pattern separation task, which might indicate a contribution of various alterations to the mnemonic deficits or the key contribution of other structures to the function. we established for the first time the alterations in both the volume and the microstructure at the level of the hippocampal subfields in a group of unilateral MTLE patients. We observed that these changes are greater in the DG and CA1 at the macrostructural level, and in CA3 and CA1 in the microstructural level. None of these changes had a direct relation to the performance of the patients in a pattern separation task, which suggests a contribution of various alterations to the loss of function

Aggregating Centrality Rankings: A Novel Approach to Detect Critical Infrastructure Vulnerabilities

Assessing critical infrastructure vulnerabilities is paramount to arrange efficient plans for their protection. Critical infrastructures are network-based systems hence, they are composed of nodes and edges. The literature shows that node criticality, which is the focus of this paper, can be addressed from different metric-based perspectives (e.g., degree, maximal flow, shortest path). However, each metric provides a specific insight while neglecting others. This paper attempts to overcome this pitfall through a methodology based on ranking aggregation. Specifically, we consider several numerical topological descriptors of the nodes’ importance (e.g., degree, betweenness, closeness, etc.) and we convert such descriptors into ratio matrices; then, we extend the Analytic Hierarchy Process problem to the case of multiple ratio matrices and we resort to a Logarithmic Least Squares formulation to identify an aggregated metric that represents a good tradeoff among the different topological descriptors. The procedure is validated considering the Central London Tube network as a case study

La incuestionabilidad del riesgo

Con anterioridad a la década de 1980, la literatura especializada en análisis y gestión del riesgo estaba dominada por la llamada visión tecnocrática o dominante. Esta visión establecía que los desastres naturales eran sucesos físicos extremos, producidos por una naturaleza caprichosa, externos a lo social y que requerían soluciones tecnológicas y de gestión por parte de expertos. Este artículo se centra en desarrollar una nueva explicación para entender la persistencia hegemónica de la visión tecnocrática basada en el concepto de incuestionabilidad del riesgo. Esta propuesta conceptual hace referencia a la incapacidad y desidia de los expertos, científicos y tomadores de decisiones en general (claimmakers) de identificar y actuar sobre las causas profundas de la producción del riesgo ya que ello conllevaría a cuestionar los imperativos normativos, las necesidades de las elites y los estilos de vida del actual sistema socioeconómico globalizado.Before de 1980s, the natural hazard analysis and management specialized literature was dominated by the so called "dominant" or "technocratic" view. Such perspective had established that natural disasters are extreme physical events caused by a whimsical nature and that these events are external to society. These events required technological and management solutions developed by experts. The current article aims at addressing a new explanatory component in the hegemonic persistence of the technocratic view. Such assumption was based on the "unquestionability of the risk" concept. It is stated that the "unquestionability of the risk" is the overall incapacity and neglect of experts, scientists and decision makers to identify and act over the deep causes of risk production, since it would make them question the normative imperatives and the demands from the elite as well as the life style in nowadays globalized socio-economic system