El proceso de descubrimiento de fármacos en Janssen: Diseño de mGlu2Nams

Susana Conde es actualmente “Principal Scientist” y Team Leader del departamento de Química Médica de Janssen en España. Su trayectoria investigadora ha sido brillante, siendo doctora en Química Orgánica por la Universidad de La Coruña en el año 2000 trabajando en síntesis de fosfono-aminoácidos como antagonistas competitivos del receptor NMDA. Tras su etapa predoctoral, realizó una estancia postdoctoral en el periodo 2000-2002 en el grupo del profesor Julius Rebek en el instituto Scripps en California donde trabajó en síntesis de péptido miméticos helicoidales. Entre 2002 y 2005, trabajó para la empresa Kemia Inc en California sobre varios programas de descubrimiento de fármacos en el área de HIV e inflamación. Finalmente, en 2005, la doctora Conde se unió a Janssen Pharmaceutica en España donde ha sido una persona esencial en la identificación y desarrollo de varios candidatos de los programas mGluR y PDE, relacionados con el tratamiento del Alzheimer. Es coautora de unas 40 contribuciones científicas entre artículos y patentes. La conferencia de la doctora Conde puede ser de gran interés no solo para el personal del departamento, por la relevancia científica de sus trabajos, sino también para los alumnos de grado de últimos cursos que podrán adquirir una visión de cómo es la investigación en el mundo de la empresa farmacéutica. Se programará la conferencia a las 12:30 con el objeto de que los alumnos, a los que se avisarán, puedan asistir.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Engineered MRI nanoprobes based on superparamagnetic iron oxide nanoparticles

This project aimed to engineer new T2 MRI contrast agents for cell labeling based on formulations containing monodisperse iron oxide magnetic nanoparticles (MNP) coated with natural and synthetic polymers. Monodisperse MNP capped with hydrophobic ligands were synthesized by a thermal decomposition method, and further stabilized in aqueous media with citric acid or meso-2,3-dimercaptosuccinic acid (DMSA) through a ligand exchange reaction. Hydrophilic MNP-DMSA, with optimal hydrodynamic size distribution, colloidal stability and magnetic properties, were used for further functionalization with different coating materials. A covalent coupling strategy was devised to bind the biopolymer gum Arabic (GA) onto MNPDMSA and produce an efficient contrast agent, which enhanced cellular uptake in human colorectal carcinoma cells (HCT116 cell line) compared to uncoated MNP-DMSA. A similar protocol was employed to coat MNP-DMSA with a novel biopolymer produced by a biotechnological process, the exopolysaccharide (EPS) Fucopol. Similar to MNP-DMSA-GA, MNP-DMSA-EPS improved cellular uptake in HCT116 cells compared to MNP-DMSA. However, MNP-DMSA-EPS were particularly efficient towards the neural stem/progenitor cell line ReNcell VM, for which a better iron dose-dependent MRI contrast enhancement was obtained at low iron concentrations and short incubation times. A combination of synthetic and biological coating materials was also explored in this project, to design a dynamic tumortargeting nanoprobe activated by the acidic pH of tumors. The pH-dependent affinity pair neutravidin/iminobiotin, was combined in a multilayer architecture with the synthetic polymers poy-L-lysine and poly(ethylene glycol) and yielded an efficient MRI nanoprobe with ability to distinguish cells cultured in acidic pH conditions form cells cultured in physiological pH conditions

Perceptual elements in Penn & Teller’s “Cups and Balls” magic trick

Magic illusions provide the perceptual and cognitive scientist with a toolbox of experimental manipulations and testable hypotheses about the building blocks of conscious experience. Here we studied several sleight-of-hand manipulations in the performance of the classic “Cups and Balls” magic trick (where balls appear and disappear inside upside-down opaque cups). We examined a version inspired by the entertainment duo Penn & Teller, conducted with three opaque and subsequently with three transparent cups. Magician Teller used his right hand to load (i.e. introduce surreptitiously) a small ball inside each of two upside-down cups, one at a time, while using his left hand to remove a different ball from the upside-down bottom of the cup. The sleight at the third cup involved one of six manipulations: (a) standard maneuver, (b) standard maneuver without a third ball, (c) ball placed on the table, (d) ball lifted, (e) ball dropped to the floor, and (f) ball stuck to the cup. Seven subjects watched the videos of the performances while reporting, via button press, whenever balls were removed from the cups/table (button “1”) or placed inside the cups/on the table (button “2”). Subjects’ perception was more accurate with transparent than with opaque cups. Perceptual performance was worse for the conditions where the ball was placed on the table, or stuck to the cup, than for the standard maneuver. The condition in which the ball was lifted displaced the subjects’ gaze position the most, whereas the condition in which there was no ball caused the smallest gaze displacement. Training improved the subjects’ perceptual performance. Occlusion of the magician’s face did not affect the subjects’ perception, suggesting that gaze misdirection does not play a strong role in the Cups and Balls illusion. Our results have implications for how to optimize the performance of this classic magic trick, and for the types of hand and object motion that maximize magic misdirection

Musicoterapia con neonatos prematuros en la nidad de cuidados intensivos neonatales

Estudio del efecto a corto plazo de la musicoterapia aplicada a un grupo de neonatos prematuros ingresados en la Unidad de Cuidados Intensivos Neonatales del Hospital Río Hortega de Valladolid. Se estudiaron variables de los neonatos como frecuencia cardíaca, frecuencia respiratoria, saturación de oxígeno, etc. y también variables de las madres como optimismo disposicional y ansiedad estado, estas últimas para comprobar su implicación en la evolución de los prematuros. Los resultados muestran efectos positivos de la musicoterapia a corto plazo. Estos resultados deberán comprobarse con muestras más amplias. Actualmente la musicoterapia en nuestro país es una ciencia en desarrollo, por ello, la investigación es escasa y muy variada en su temática. Sin embargo, en otros países la figura del musicoterapeuta dentro de las Unidades de Cuidados Intensivos Neonatales está implantada y su labor es importante en la evolución de los pacientes ingresados y sus familiares. La llegada de un nuevo hijo es un momento de crisis que altera la funcionalidad de la familia, esta crisis es aún mayor cuando el neonato está enfermo y es ingresado en la Unidad de Cuidados Intensivos Neonatales. Tras el parto los padres deben adaptarse a un medio extraño, enfrentándose a situaciones que no pueden controlar por sí mismos y pasan a depender del cuadro médico que los atiende, de esta forma se altera temporalmente su rol de padres y el temor y la ansiedad son compañeros habituales. En este contexto el apoyo emocional, la reducción del estrés y la ansiedad, la relajación, etc. son actuaciones necesarias para mejorar el estado emocional de los padres y la evolución de los prematuros. La musicoterapia es una disciplina, que en conjunto con otro tipo de actuaciones y cuidados, puede ayudar y apoyar la salud de los neonatos y sus padres. El objetivo general de esta investigación es conocer si la música en vivo influye de alguna manera en el estado de los neonatos prematuros ingresados en la Unidad de Cuidados Intensivos Neonatales y sus familias.Departamento de Pedagogí

El profesorado universitario ante la e-evaluación del aprendizaje

El artículo se enmarca en el campo de la eevaluación en la Universidad. Se pretende identificar cómo se gestiona el proceso de evaluación de los estudiantes y, a la vez, conocer la actitud de los docentes universitarios hacia la incorporación de las tecnologías en el proceso de evaluación de aprendizajes. La metodología descriptiva-correlacional empleada se basa en la aplicación de una encuesta electrónica a una muestra representativa por rama y categoría profesional de docentes en la Universidad de Salamanca. Los resultados obtenidos, tras la realización de los contrastes inferenciales oportunos de “actitud” por rama de conocimiento, categoría profesional y años de docencia, muestran diferencias estadísticamente significativas por rama de conocimiento

Microsaccades in applied environments: Real-world applications of fixational eye movement measurements

Across a wide variety of research environments, the recording of microsaccades and other fixational eye movements has provided insight and solutions into practical problems. Here we review the literature on fixational eye movements—especially microsaccades—in applied and ecologically-valid scenarios. Recent technical advances allow noninvasive fixational eye movement recordings in real-world contexts, while observers perform a variety of tasks. Thus, fixational eye movement measures have been obtained in a host of real-world scenarios, such as in connection with driver fatigue, vestibular sensory deprivation in astronauts, and elite athletic training, among others. Here we present the state of the art in the practical applications of fixational eye movement research, examine its potential future uses, and discuss the benefits of including microsaccade measures in existing eye movement detection technologies. Current evidence supports the inclusion of fixational eye movement measures in real-world contexts, as part of the development of new or improved oculomotor assessment tools. The real-world applications of fixational eye movement measurements will only grow larger and wider as affordable high-speed and high-spatial resolution eye trackers become increasingly prevalent

Rapid Dynamics of Contrast Responses in the Cat Primary Visual Cortex

The visual information we receive during natural vision changes rapidly and continuously. The visual system must adapt to the spatiotemporal contents of the environment in order to efficiently process the dynamic signals. However, neuronal responses to luminance contrast are usually measured using drifting or stationary gratings presented for a prolonged duration. Since motion in our visual field is continuous, the signals received by the visual system contain an abundance of transient components in the contrast domain. Here using a modified reverse correlation method, we studied the properties of responses of neurons in the cat primary visual cortex to different contrasts of grating stimuli presented statically and transiently for 40 ms, and showed that neurons can effectively discriminate the rapidly changing contrasts. The change in the contrast response function (CRF) over time mainly consisted of an increment in contrast gain (CRF shifts to left) in the developing phase of temporal responses and a decrement in response gain (CRF shifts downward) in the decay phase. When the distribution range of stimulus contrasts was increased, neurons demonstrated decrement in contrast gain and response gain. Our results suggest that contrast gain control (contrast adaptation) and response gain control mechanisms are well established during the first tens of milliseconds after stimulus onset and may cooperatively mediate the rapid dynamic responses of visual cortical neurons to the continuously changing contrast. This fast contrast adaptation may play a role in detecting contrast contours in the context of visual scenes that are varying rapidly

The influence of nitric oxide on perigeniculate GABAergic cell activity in the anaesthetized cat

[Abstract] We have tested the effect of iontophoretic application of the nitric oxide synthase inhibitor l-nitroarginine on the activity of a population of 53 perigeniculate (PGN) cells, recorded extracellularly in the anaesthetized paralysed cat. In all cells tested with visual stimulation during l-nitroarginine application (n= 15), the visually elicited responses were markedly reduced, on average by 63 ± 15%, and there was a reduction in spontaneous activity too. This effect was blocked by co-application of the substrate for nitric oxide synthase, l-arginine, but not by the inactive d-isoform, although application of l-arginine alone was without effect. Pressure application of the nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP) elevated both visual responses and spontaneous discharge, an effect also seen with a second nitric oxide donor, sodium nitroprusside (n= 12). The nitric oxide synthase inhibitor l-nitroarginine was applied to a sub-population of seven cells and it selectively decreased NMDA mediated excitation (reduction 80 % 14%) with little or no effect on the excitation mediated by α-amino-3-hydroxy-5-5-methyl-4-isoxazole-propionic acid (AMPA) or quisqualate (effects not statistically significant), and it had no effect (n= 7) on excitation mediated by the metabotropic agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD). Furthermore, application of SNAP also increased the magnitude of excitatory responses mediated by NMDA receptors. On a different population of seven cells, application of the new NO donor diethylamine-nitric oxide (DEA-NO) enhanced the actions Of NMDA without an effect on responses to AMPA. These effects are qualitatively and quantitatively similar to those we have previously described for X and Y type cells in the dorsal lateral geniculate nucleus (dLGN), despite the known opposite effects of acetylcholine (ACh) application in the dLGN and PGN (ACh is co-localized with nitric oxide synthase at both sites). We propose that within the PGN nitric oxide acts to enhance transmission utilizing NMDA receptors selectively (thereby interacting with the globally inhibiting effect of ACh at this site) to enhance visual responses, reducing or removing the non-specific inhibitory drive from PGN to dLGN seen in the spindling activity of slow-wave sleep. These effects will act in concert with the facilitatory actions of both ACh and nitric oxide within the dLGN proper, and will thereby enhance the faithful transmission of visual information from retina to cortex.Ministerio de Educación y Ciencia; PB93-034

A transformação digital das escolas e o seu impacto nas estruturas de gestão escolar, administrativas, pedagógicas e tecnológicas: estudo de caso

A transformação digital é um conceito cada vez mais presente nas instituições, não apenas como um processo que permite usar recursos tecnológicos para aumentar o desempenho organizacional, mas também como uma mudança cultural. O propósito deste estudo é analisar que transformações organizacionais, administrativas, tecnológicas e pedagógicas resultam da transformação digital das escolas e que impacto teve a pandemia de Covid-19 neste processo. Tendo em conta a complexidade e amplitude do tema, decidimos focar a investigação num estudo de caso num agrupamento de escolas. A recolha de dados baseou-se num modelo de triangulação, sendo a informação recolhida através de análise documental, de uma entrevista semiestruturada à diretora do agrupamento e de questionários aos docentes. A transformação digital no agrupamento em estudo já vinha a acontecer de forma gradual, na área administrativa e no apoio ao ensino nas salas de aula, com a necessidade de suspensão das atividades letivas devido à pandemia de Covid-19 a tecnologia ganhou um papel de destaque. Foi necessário organizar, reinventar e encontrar recursos para que escola não parasse e para que os alunos continuassem a aprender. O ensino remoto de emergência foi a alternativa possível, deixando em aberto para o futuro da escola possibilidades, experiências e conhecimento para um ensino mais digital. A capacitação do corpo docente é fundamental para uma atuação competente neste novo caminho. Este caminho da transformação digital está a ser feito, todavia ainda falta investimento tecnológico em equipamentos adequados e eficazes e formação de professores que dê resposta a este desafio.Digital transformation is a concept increasingly present in institutions, not only as a process that allows using technological resources to increase organizational performance, but also as a cultural change. The purpose of this study is to analyze what organizational, administrative, technological, and pedagogical transformations result from the digital transformation of schools and what impact the Covid-19 pandemic has had on this process. Given the complexity and breadth of the topic, we decided to focus the research on a case study in one school cluster. Data collection was based on a triangulation model, with information collected through document analysis, a semi-structured interview with the cluster's director, and questionnaires to teachers. The digital transformation in the school cluster under study was already happening gradually, in the administrative area and in supporting teaching in the classrooms, but with the need to suspend school activities due to the Covid-19 pandemic, technology gained a prominent role. It was necessary to organize, reinvent, and find resources so that school would not stop and students would continue to learn. Emergency remote teaching was the possible alternative, leaving open for the future of the school possibilities, experiences, and knowledge for a more digital education. Training the teaching staff is essential to perform competently on this new path. This path of digital transformation is being taken, however, there is still a lack of technological investment in adequate and effective equipment and teacher training to meet this challenge