Type III Secretion Effectors with Arginine N-Glycosyltransferase Activity

Type III secretion systems are used by many Gram-negative bacterial pathogens to inject proteins, known as effectors, into the cytosol of host cells. These virulence factors interfere with a diverse array of host signal transduction pathways and cellular processes. Many effectors have catalytic activities to promote post-translational modifications of host proteins. This review focuses on a family of effectors with glycosyltransferase activity that catalyze addition of N-acetyl-d-glucosamine to specific arginine residues in target proteins, leading to reduced NF-κB pathway activation and impaired host cell death. This family includes NleB from Citrobacter rodentium, NleB1 and NleB2 from enteropathogenic and enterohemorrhagic Escherichia coli, and SseK1, SseK2, and SseK3 from Salmonella enterica. First, we place these effectors in the general framework of the glycosyltransferase superfamily and in the particular context of the role of glycosylation in bacterial pathogenesis. Then, we provide detailed information about currently known members of this family, their role in virulence, and their targetsSpanish Ministerio de Economía, Industria y Competitividad , Agencia Estatal de Investigación, and the European Regional Development Fund, grant number SAF2016‐75365‐REuropean Union’s Horizon 2020 e Marie Skłodowska‐Curie grant agreement No 84262

Deep Neural Networks for the Recognition and Classification of Heart Murmurs Using Neuromorphic Auditory Sensors

Auscultation is one of the most used techniques for detecting cardiovascular diseases, which is one of the main causes of death in the world. Heart murmurs are the most common abnormal finding when a patient visits the physician for auscultation. These heart sounds can either be innocent, which are harmless, or abnormal, which may be a sign of a more serious heart condition. However, the accuracy rate of primary care physicians and expert cardiologists when auscultating is not good enough to avoid most of both type-I (healthy patients are sent for echocardiogram) and type-II (pathological patients are sent home without medication or treatment) errors made. In this paper, the authors present a novel convolutional neural network based tool for classifying between healthy people and pathological patients using a neuromorphic auditory sensor for FPGA that is able to decompose the audio into frequency bands in real time. For this purpose, different networks have been trained with the heart murmur information contained in heart sound recordings obtained from nine different heart sound databases sourced from multiple research groups. These samples are segmented and preprocessed using the neuromorphic auditory sensor to decompose their audio information into frequency bands and, after that, sonogram images with the same size are generated. These images have been used to train and test different convolutional neural network architectures. The best results have been obtained with a modified version of the AlexNet model, achieving 97% accuracy (specificity: 95.12%, sensitivity: 93.20%, PhysioNet/CinC Challenge 2016 score: 0.9416). This tool could aid cardiologists and primary care physicians in the auscultation process, improving the decision making task and reducing type-I and type-II errors.Ministerio de Economía y Competitividad TEC2016-77785-

NAVIS: Neuromorphic Auditory VISualizer Tool

This software presents diverse utilities to perform the first post-processing layer taking the neuromorphic auditory sensors (NAS) information. The used NAS implements in FPGA a cascade filters architecture, imitating the behavior of the basilar membrane and inner hair cells and working with the sound information decomposed into its frequency components as spike streams. The well-known neuromorphic hardware interface Address-Event-Representation (AER) is used to propagate auditory information out of the NAS, emulating the auditory vestibular nerve. Using the information packetized into aedat files, which are generated through the jAER software plus an AER to USB computer interface, NAVIS implements a set of graphs that allows to represent the auditory information as cochleograms, histograms, sonograms, etc. It can also split the auditory information into different sets depending on the activity level of the spike streams. The main contribution of this software tool is that it allows complex audio post-processing treatments and representations, which is a novelty for spike-based systems in the neuromorphic community and it will help neuromorphic engineers to build sets for training spiking neural networks (SNN).Ministerio de Economía y Competitividad TEC2012-37868-C04-0

A theoretical structure-affinity relationship study of some cannabinoid derivatives

Indexación: ScieloA ZINDO/1 quantum-chemical structure-affinity relationship study with the KPG model is presented for the in vitro interaction of a group of classical, indole-derived and aminoalkylindole-derived cannabinoids with CB and CB2 receptors. From this work the following conclusions are obtained. CB and CB2 CB2 receptor affinities are regulated by different mechanisms involving orbital and charge control. Nevertheless CB and CB2 classical ligands share three common features: a hydrogen bond to a lysine (for CB ) or serine (for CB), a fully aromatic ring and a branched carbon side chain. In the case of indole-derived and aminoalkylindole-derived cannabinoids orientation and alignment rules have been defined as a basis for the comparison of noncongeneric molecules. In this way it was possible to associate the location of molecular fragments of these systems with known molecular systems such as classical cannabinoids. For aminoalkyhndoles we have proposed the locus with which they bind to a second receptor site that is available to WIN-55212-2 but not to classical cannabinoids. On the basis of our results we propose a new molecule that should help to discriminate between the above two receptor sites.http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-97072008000100013&nrm=is

A Sensor Fusion Horse Gait Classification by a Spiking Neural Network on SpiNNaker

The study and monitoring of the behavior of wildlife has always been a subject of great interest. Although many systems can track animal positions using GPS systems, the behavior classification is not a common task. For this work, a multi-sensory wearable device has been designed and implemented to be used in the Doñana National Park in order to control and monitor wild and semiwild life animals. The data obtained with these sensors is processed using a Spiking Neural Network (SNN), with Address-Event-Representation (AER) coding, and it is classified between some fixed activity behaviors. This works presents the full infrastructure deployed in Doñana to collect the data, the wearable device, the SNN implementation in SpiNNaker and the classification results.Ministerio de Economía y Competitividad TEC2012-37868-C04-02Junta de Andalucía P12-TIC-130

Stereo Matching in Address-Event-Representation (AER) Bio-Inspired Binocular Systems in a Field-Programmable Gate Array (FPGA)

In stereo-vision processing, the image-matching step is essential for results, although it involves a very high computational cost. Moreover, the more information is processed, the more time is spent by the matching algorithm, and the more ine cient it is. Spike-based processing is a relatively new approach that implements processing methods by manipulating spikes one by one at the time they are transmitted, like a human brain. The mammal nervous system can solve much more complex problems, such as visual recognition by manipulating neuron spikes. The spike-based philosophy for visual information processing based on the neuro-inspired address-event-representation (AER) is currently achieving very high performance. The aim of this work was to study the viability of a matching mechanism in stereo-vision systems, using AER codification and its implementation in a field-programmable gate array (FPGA). Some studies have been done before in an AER system with monitored data using a computer; however, this kind of mechanism has not been implemented directly on hardware. To this end, an epipolar geometry basis applied to AER systems was studied and implemented, with other restrictions, in order to achieve good results in a real-time scenario. The results and conclusions are shown, and the viability of its implementation is proven.Ministerio de Economía y Competitividad TEC2016-77785-

System based on inertial sensors for behavioral monitoring of wildlife

Sensors Network is an integration of multiples sensors in a system to collect information about different environment variables. Monitoring systems allow us to determine the current state, to know its behavior and sometimes to predict what it is going to happen. This work presents a monitoring system for semi-wild animals that get their actions using an IMU (inertial measure unit) and a sensor fusion algorithm. Based on an ARM-CortexM4 microcontroller this system sends data using ZigBee technology of different sensor axis in two different operations modes: RAW (logging all information into a SD card) or RT (real-time operation). The sensor fusion algorithm improves both the precision and noise interferences.Junta de Andalucía P12-TIC-130

Perceptions of Self-concept and Self-presentation by Procrastinators: Further Evidence

Two samples of university students completed self-report measures of chronic procrastination and either self-concept variables (Sample 1, n = 233) or self-presentational styles (Sample 2, n = 210). Results indicated that procrastination was significantly related to a self-concept of oneself as dominated by issues related to task performance, and to self presentation strategies that reflected a person as continually justifying and excusing task delays and being “needy” of others’ approval. It seems that men and women procrastinate in order to improve their social standing by making their accomplishments seem greater than they really are.Dos muestras de estudiantes universitarios completaron auto-informes de procrastinación crónica y de variables de auto concepto (Muestra 1, n = 233) o de estilos de autopresentación (Muestra 2, n = 210). Los resultados indicaron que la procrastinación se relaciona significativamente con el auto-concepto de una persona que se siente dominada por los asuntos relacionados con la ejecución de tareas, y con estrategias de autopresentación que reflejan una persona que constantemente justifica y excusa los retrasos en las tareas y necesita la aprobación de los demás. Parece que los hombres y las mujeres procrastinan para mejorar su estatus social haciendo que sus logros parezcan más importantes de lo que realmente son

Morningness-eveningness in adolescents

Individual morningness-eveningness differences explain the rhythmic variations of behavioral and biological patterns. Several studies have corroborated that morningness preference increases over adulthood and aging. Adolescents shift their time of day preferences from morningness to eveningness during puberty. The aims of this study were translate to Spanish the Morningness-Eveningness Scale for Children (MESC) and to analyze age and sex differences. A group of 600 adolescents (aged between 12 and 16 years) participated in the study. Psychometric analysis showed that reliability and factor structure were suitable and similar to previous studies. The results indicated a clear decrease of morningness as of 12 years. Boys were more morningness-oriented than girls in several items of the questionnaire. In view of the results, several educational implications are raised.La tendencia a la matutinidad-vespertinidad permite explicar gran parte de las variaciones rítmicas de patrones biológicos y conductuales. Se ha constatado que con la edad se produce un incremento paulatino de la matutinidad. En población adolescente se ha detectado una mayor tendencia a la vespertinidad. Los objetivos del estudio fueron la traducción y adaptación del Morningness-Eveningness Scale for Children (MESC) a población adolescente, así como el análisis de las diferencias de edad y sexo. En el estudio participaron 600 adolescentes entre 12 y 16 años. Los resultados indicaron que el MESC es un instrumento fiable en población adolescente, siendo su estructura factorial similar a la obtenida en otros estudios. A partir de los 12 años se producía una disminución progresiva de la matutinidad, siendo esta disminución mayor para las mujeres que para los varones en algunos elementos del cuestionario. Se plantean algunas implicaciones educativas a raíz de los resultados obtenidos

Desarrollo de filtros <i>in silico</i> orientados a optimizar el desarrollo de nuevos fármacos destinados al sistema nervioso central

La incidencia y costo socioeconómico de los desórdenes del sistema nervioso central (SNC) se está incrementando de manera alarmante en las últimas décadas. Por otro lado, el descubrimiento y desarrollo de nuevos fármacos destinados al SNC es una de las áreas más riesgosas, con los mayores índices de fracaso. La barrera hematoencefálica (BHE) constituye uno de los principales obstáculos farmacocinéticos para el éxito de la terapia dirigida al SNC, ya que impone serias dificultades para la biodistribución de los fármacos a sus blancos moleculares en el cerebro. Por lo tanto, durante el desarrollo de nuevos fármacos para el tratamiento de trastornos del SNC resulta de suma importancia la evaluación de la capacidad de los mismos para atravesar eficazmente la BHE y así lograr niveles terapéuticos en el cerebro. En el presente trabajo de tesis nos hemos propuesto el desarrollo de modelos computacionales para predecir el parámetro farmacocinético Kp,uu, el cual está asociado al pasaje de fármacos a través de la BHE. El proceso para la generación de los modelos se estructuró en dos etapas bien diferenciadas. En una primera instancia, se compiló un conjunto de datos de compuestos con valores de Kp,uu obtenidos en estado estacionario por cualquiera de las tres metodologías experimentales disponibles para dicho fin: Microdialisis, Slice y Homogenato (conjunto de datos MSH). Dicha base de datos MSH se utilizó para generar modelos clasificatorios mediante el uso de distintos algoritmos, algunos de los cuales lograron discernir adecuadamente entre compuestos de baja y alta biodisponibilidad de fármaco libre en el SNC. Todos los modelos fueron validados computacionalmente y demostraron un buen poder predictivo. Se validó también experimental y prospectivamente el modelo individual seleccionado como el mejor. Para ello se determinó experimentalmente el parámetro Kp,uu mediante la técnica de homogenato de cinco compuestos que no habían formado parte del conjunto de datos original. La tasa de buenas clasificaciones fue de 80,0% (4/5) para la validación experimental prospectiva. Para la segunda etapa de desarrollo de modelos se consideraron únicamente aquellos valores de Kp,uu obtenidos por las técnicas de Microdialisis y/o Slice. Se conformó así un nuevo conjunto de datos (conjunto MS), con el objetivo de disminuir la variabilidad/ruido de la base de datos a utilizar en la obtención de los modelos. La misma metodología de modelado generó modelos con mejor poder predictivo que los obtenidos con el conjunto MSH. En esta oportunidad la validación prospectiva del mejor modelo individual se llevó a cabo desde un enfoque diferente al descripto para el conjunto de datos MSH. Se utilizaron compuestos que no formaron parte del conjunto de datos MS, y cuyos datos observados del parámetro modelado fueron obtenidos de diferentes maneras: datos publicados con posterioridad al armado del conjunto de datos MS y datos proporcionados por la Escuela de Medicina de la Universidad de Indiana (EE. UU.). De esta forma, el conjunto de datos para esta nueva validación prospectiva quedó conformado por 10 compuestos. De éstos, 9 fueron bien clasificados por el mejor modelo, lo que representó una de tasa de buenas clasificaciones del 90,0%. El uso de estos modelos computacionales como filtros in silico durante el desarrollo de nuevos medicamentos para el tratamiento de las enfermedades del SNC, podría optimizar la utilización de recursos y, por ende, disminuir el impacto de la baja en la inversión sufrida en los últimos tiempos en dicha área terapéutica.Facultad de Ciencias Exacta