Endothelial NOX5 overexpression induces changes in the cardiac gene profile: potential impact in myocardial infarction?

Cardiovascular diseases and the ischemic heart disease specifically constitute the main cause of death worldwide. The ischemic heart disease may lead to myocardial infarction, which in turn triggers numerous mechanisms and pathways involved in cardiac repair and remodeling. Our goal in the present study was to characterize the effect of the NADPH oxidase 5 (NOX5) endothelial expression in healthy and infarcted knock-in mice on diverse signaling pathways. The mechanisms studied in the heart of mice were the redox pathway, metalloproteinases and collagen pathway, signaling factors such as NFκB, AKT or Bcl-2, and adhesion molecules among others. Recent studies support that NOX5 expression in animal models can modify the environment and predisposes organ response to harmful stimuli prior to pathological processes. We found many alterations in the mRNA expression of components involved in cardiac fibrosis as collagen type I or TGF-β and in key players of cardiac apoptosis such as AKT, Bcl-2, or p53. In the heart of NOX5-expressing mice after chronic myocardial infarction, gene alterations were predominant in the redox pathway (NOX2, NOX4, p22phox, or SOD1), but we also found alterations in VCAM-1 and β-MHC expression. Our results suggest that NOX5 endothelial expression in mice preconditions the heart, and we propose that NOX5 has a cardioprotective role. The correlation studies performed between echocardiographic parameters and cardiac mRNA expression supported NOX5 protective action. (AU)

Endothelial NOX5 overexpression induces changes in the cardiac gene profile: potential impact in myocardial infarction?

Cardiovascular diseases and the ischemic heart disease specifically constitute the main cause of death worldwide. The ischemic heart disease may lead to myocardial infarction, which in turn triggers numerous mechanisms and pathways involved in cardiac repair and remodeling. Our goal in the present study was to characterize the effect of the NADPH oxidase 5 (NOX5) endothelial expression in healthy and infarcted knock-in mice on diverse signaling pathways. The mechanisms studied in the heart of mice were the redox pathway, metalloproteinases and collagen pathway, signaling factors such as NFκB, AKT or Bcl-2, and adhesion molecules among others. Recent studies support that NOX5 expression in animal models can modify the environment and predisposes organ response to harmful stimuli prior to pathological processes. We found many alterations in the mRNA expression of components involved in cardiac fibrosis as collagen type I or TGF-ß and in key players of cardiac apoptosis such as AKT, Bcl-2, or p53. In the heart of NOX5-expressing mice after chronic myocardial infarction, gene alterations were predominant in the redox pathway (NOX2, NOX4, p22phox, or SOD1), but we also found alterations in VCAM-1 and ß-MHC expression. Our results suggest that NOX5 endothelial expression in mice preconditions the heart, and we propose that NOX5 has a cardioprotective role. The correlation studies performed between echocardiographic parameters and cardiac mRNA expression supported NOX5 protective action.

NADPH Oxidase 5 (NOX5) Overexpression Promotes Endothelial Dysfunction via Cell Apoptosis, Migration, and Metabolic Alterations in Human Brain Microvascular Endothelial Cells (hCMEC/D3).

NADPH oxidases (NOX) constitute the main reactive oxygen species (ROS) source in blood vessels. An oxidative stress situation due to ROS overproduction can lead into endothelial dysfunction, a molecular mechanism that precedes cardiovascular diseases (CVDs) such as atherosclerosis, myocardial infarction, and stroke. NOX5 is the last discovered member of the NOX family, studied in a lesser extent due to its absence in the rodent genome. Our objective was to describe the phenotypic alterations produced by an oxidative stress situation derived from NOX5 overexpression in an endothelial in vitro model. The in vitro model consists of the hCMEC/D3 cell line, derived from brain microvascular endothelium, infected with a recombinant NOX5-ß adenovirus. After an initial proteomic analysis, three phenotypic alterations detected in silico were studied: cell proliferation and apoptosis, general and mitochondrial metabolism, and migration capacity. NOX5 infection of hCMEC/D3 generates a functional protein and an increase in ROS production. This model produced changes in the whole cell proteome. The in silico analysis together with in vitro validations demonstrated that NOX5 overexpression inhibits proliferation and promotes apoptosis, metabolic alterations and cell migration in hCMEC/D3 cells. NOX5 overexpression in endothelial cells leads to phenotypic changes that can lead to endothelial dysfunction, the onset of atherosclerosis, myocardial infarction, and stroke.

Expression of Endothelial NOX5 Alters the Integrity of the Blood-Brain Barrier and Causes Loss of Memory in Aging Mice.

Blood-Brain barrier (BBB) disruption is a hallmark of central nervous system (CNS) dysfunction, and oxidative stress is one of the molecular mechanisms that may underlie this process. NADPH oxidases (NOX) are involved in oxidative stress-mediated vascular dysfunction and participate in the pathophysiology of its target organs. The NADPH oxidase 5 (NOX5) isoform is absent in rodents, and although little is known about the role it may play in disrupting the BBB, it has recently been implicated in experimental stroke. Our aim was to investigate the role of NADPH oxidase 5 (NOX5) in promoting vascular alterations and to identify its impact on the cognitive status of aged mice. No differences were detected in the arterial blood pressure or body weight between knock-in mice expressing endothelial NOX5 and the control mice. The Morris water maze test showed memory impairments in the aged knock-in mice expressing NOX5 compared with their control littermates. For assessing the BBB integrity, we studied the protein expression of two tight junction (TJ) proteins: Zonula occludens-1 (ZO-1) and occludin. Compared to the control animals, Aged NOX5 mice exhibited reduced levels of both proteins, demonstrating an alteration of the BBB integrity. Our data indicate that vascular NOX5 may favor behavioral changes with aging through oxidative stress-mediated BBB breakdown.

NADPH Oxidase 5 Induces Changes in the Unfolded Protein Response in Human Aortic Endothelial Cells and in Endothelial-Specific Knock-in Mice.

Oxidative stress constitutes a key molecular mechanism in the development of cardiovascular diseases. A potential relationship between reactive oxygen species (ROS) driven by the NADPH oxidase family (NOX) and the unfolded protein response (UPR) has been postulated. Nevertheless, there is a lack of information about the crosstalk between NOX5 homologue and the UPR in a cardiovascular context. The main aim was to analyze NOX5-mediated ROS effects in the UPR and its importance in cardiovascular diseases. To this effect, we used an adenoviral NOX5-ß overexpression model in human aortic endothelial cells (HAEC) and a conditional endothelial NOX5 knock-in mouse. Using expression arrays, we investigated NOX5-induced genomic changes in HAEC. Compared with the control HAEC, 298 genes were differentially expressed. Gene ontology analysis revealed the activation of numerous cellular routes, the most relevant being the UPR pathway. Using real-time PCR and Western Blot experiments, we confirmed that NOX5 overexpression induced changes in the expression of the UPR components, which were associated with increased apoptosis. Moreover, in endothelial-specific NOX5 knock-in mice, we found changes in the expression of the UPR components genes. In these mice, myocardial infarction was performed by permanent coronary artery ligation; however, NOX5 expression was not associated with differences in the UPR components mRNA levels. In these animals, we found significant associations between the UPR components gene expression and echocardiographic parameters. Our data support the idea that NOX5-derived ROS may modulate the UPR pathway in endothelial cells, which might play a relevant role in cardiac physiology.

Cognitive and behavioral profiles of pediatric surgical candidates with frontal and temporal lobe epilepsy.

BACKGROUND: We aimed to prospectively analyze memory and executive and social cognitive functioning in patients with drug-resistant frontal lobe epilepsy (FLE) and temporal lobe epilepsy (TLE) with focal lesions and isolate the impact of intellectual ability on specific deficits. METHODS: A neuropsychological evaluation was performed in 23 children with FLE, 22 children with TLE, and 36 healthy pediatric controls (HCs). Patients in the epilepsy groups had a range of lesions, including low-grade epilepsy-associated tumors (LEAT), focal cortical dysplasia (FCD) type II, and mesial temporal sclerosis (MS). RESULTS: There were no significant differences between children with FLE and TLE regarding memory, executive, or social cognitive functioning. General Ability Index (GAI) was a predictor of memory, executive function, and social cognition scores and was influenced by age at onset, duration of epilepsy, and number of antiepileptic drugs (AEDs) prescribed at the time of assessment. Working Memory Index scores of patients with TLE, which measure verbal mnesic processing, were significantly lower than those of HCs and patients with TLE. The greatest differences in both clinical groups compared to HCs were recorded in cognitive executive functions, and patients with FLE had lower scores in this domain. Regarding behavioral executive functions, patients with TLE presented impaired emotional control and impulse inhibition and patients with FLE exhibited decreased flexibility. CONCLUSION: Consistent with previous research, our findings provide further detailed evidence of small differences in cognitive performance among children with FLE and TLE. These differences emerge on analysis of the factors with which deficits are associated.

Implications of NADPH oxidase 5 in vascular diseases.

Oxidative stress is one of the main mechanisms involved in the pathophysiology of vascular diseases. Among others, oxidative stress promotes endothelial dysfunction, and accelerated ageing and remodelling of vasculature. Lately, NADPH oxidases have been demonstrated to be involved in cardiovascular diseases. NADPH oxidase 5 has emerged as a new player in oxidative stress-mediated endothelial alterations, involved in the pathophysiology of hypertension, diabetes, atherosclerosis, myocardial infarction and stroke. This oxidase seems to mediate its detrimental effects by promoting inflammation. NADPH oxidase 5 has been studied in a lesser extent compared with the other members of the NADPH oxidase family due to its loss in the rodent genome, the main experimental research model. In addition, its potential as a therapeutic target remains unexplored given the lack of specific inhibitors. In this review the latest findings on NADPH oxidase 5 regulation, implications in vascular pathophysiology and therapeutic approaches will be updated.

Induction of Cyclooxygenase-2 by Overexpression of the Human NADPH Oxidase 5 (NOX5) Gene in Aortic Endothelial Cells.

Oxidative stress is a main molecular mechanism that underlies cardiovascular diseases. A close relationship between reactive oxygen species (ROS) derived from NADPH oxidase (NOX) activity and the prostaglandin (PG) biosynthesis pathway has been described. However, little information is available about the interaction between NOX5 homolog-derived ROS and the PG pathway in the cardiovascular context. Our main goal was to characterize NOX5-derived ROS effects in PG homeostasis and their potential relevance in cardiovascular pathologies. For that purpose, two experimental systems were employed: an adenoviral NOX5-ß overexpression model in immortalized human aortic endothelial cells (TeloHAEC) and a chronic infarction in vivo model developed from a conditional endothelial NOX5 knock-in mouse. NOX5 increased cyclooxygenase-2 isoform (COX-2) expression and prostaglandin E2 (PGE2) production through nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in TeloHAEC. Protein kinase C (PKC) activation and intracellular calcium level (Ca++) mobilization increased ROS production and NOX5 overexpression, which promoted a COX-2/PGE2 response in vitro. In the chronic infarction model, mice encoding endothelial NOX5 enhanced the cardiac mRNA expression of COX-2 and PGES, suggesting a COX-2/PGE2 response to NOX5 presence in an ischemic situation. Our data support that NOX5-derived ROS may modulate the COX-2/PGE2 axis in endothelial cells, which might play a relevant role in the pathophysiology of heart infarction.

NADPH Oxidase Overactivity Underlies Telomere Shortening in Human Atherosclerosis.

Telomere shortening and oxidative stress are involved in the pathogenesis of atherosclerosis. Different studies have shown that phagocytic NADPH oxidase is associated with this disease. This study aimed to investigate the association between phagocytic NADPH oxidase and telomere shortening in human atherosclerosis. To assess this potential association, telomere length and phagocytic NADPH oxidase activity were determined by PCR and chemiluminescence, respectively, in a population of asymptomatic subjects free of overt clinical atherosclerosis. We also measured serum 8-hydroxy-2-deoxyguanosine (8-OHdG) levels (an index of oxidative stress) and carotid intima-media thickness (IMT), a surrogate marker of atherosclerosis. After adjusting them for age and sex, telomere length inversely correlated (p < 0.05) with NADPH oxidase-mediated superoxide production, with 8-OHdG values, and with carotid IMT. Interestingly, the asymptomatic subjects with plaques have a lower telomere length (p < 0.05), and higher values of plasma 8-OHdG and superoxide production (p < 0.05). These data were confirmed in a second population in which patients with coronary artery disease showed lower telomere length and higher 8-OHdG and superoxide production than the asymptomatic subjects. In both studies, NADPH oxidase-dependent superoxide production in phagocytic cells was only due to the specific expression of the Nox2 isoform. In conclusion, these findings suggest that phagocytic NADPH oxidase may be involved in oxidative stress-mediated telomere shortening, and that this axis may be critically involved in human atherosclerosis.

Evolución de las alteraciones cognitivas tras un traumatismo craneoencefálico: ¿hay mejoría tras controlar el efecto de la práctica? / Evolution of cognitive impairment after a traumatic brain injury: is there any improvement after controlling the practice effect?

Introducción: La importancia de conocer el patrón de evolución de los déficits cognitivos en los primeros meses tras un traumatismo craneoencefálico (TCE) ha fomentado el desarrollo de numerosos estudios longitudinales. Sin embargo, los resultados de la mayoría de ellos deberían tomarse con cautela debido a la falta de un control adecuado del efecto de la práctica, que puede llevar a sobreestimar la recuperación genuina de los procesos cognitivos. Objetivo: Describir los cambios cognitivos entre las fases aguda y subaguda del TCE controlando el efecto de la práctica. Pacientes y métodos: Veintidós pacientes realizaron dos evaluaciones neuropsicológicas tras el TCE (inmediata y tras seis meses) mediante los siguientes tests: Trail Making Test (A, B, B/A y B-A), test de Stroop (P, C, PC e interferencia), clave de números, búsqueda de símbolos, dígitos directos e inversos, fluidez verbal y memoria inmediata. Para controlar el efecto de la práctica se realizó una transformación de las puntuaciones aplicando el procedimiento propuesto por Calamia et al. Resultados: Antes de controlar el efecto de la práctica, se evidenció una mejoría en las puntuaciones de todos los tests (p > 0,001). Sin embargo, tras él, la mejoría permaneció sólo en el Trail Making Test-B, B/A y B-A, la clave de números, la búsqueda de símbolos, el test de Stroop PC y los dígitos inversos. Conclusiones: La falta de control del efecto de la práctica en estudios longitudinales puede generar interpretaciones erróneas sobre el perfil de evolución de los déficits cognitivos. El patrón de recuperación tras un TCE varía en función del proceso cognitivo

Introduction: The importance of knowing the pattern of evolution of cognitive deficits in the first months after a traumatic brain injury (TBI) has encouraged the development of numerous longitudinal studies. However, the results of most of them should be taken with caution due to the lack of adequate control of practice effects that can lead to overestimating the genuine recovery of cognitive processes. Aim. To describe the cognitive changes between the acute and subacute phases of the TBI controlling the effect of the practice. Patients and methods: Twenty-two patients were assessed in two different time points after TBI (immediately and after six months) using the following tests: Trail Making Test (A, B, B/A, B-A), Stroop Test (W, C, CW, interference), Digit Symbol-Coding, Symbol Search, Digits Forward and Backward, Verbal Fluency and Short-term Memory. To control for the practice effects, a transformation of the scores was performed applying the procedure proposed by Calamia et al. Results: Before controlling the practice effects, the scores of all tests improved (p > 0.001). However, afterward, the improvement remained only in the Trail Making Test-B, B/A and B-A, Digit Symbol-Coding, Symbol Search, Stroop CW and Digits Backward. Conclusions: The lack of control of practice effects in longitudinal studies can generate misleading interpretations about the evolution of cognitive deficits. The pattern of recovery after a TBI varies depending on the cognitive process

Schoolchildren's Compensatory Strategies and Skills in Relation to Attention and Executive Function App Training.

BACKGROUND: Given the importance of attention and executive functions (EF) in children's behavior, programs aimed at improving these processes are of special interest. Nexxo-training combines the use of the Nexxo touchscreen application (inhibition and vigilance tasks) with procedural metacognitive strategies (imparted by an instructor) for all the individuals using the app, regardless of their level of ability, plus compensatory strategies based on individual child performance. This study presents an analysis of the compensatory strategies that schoolchildren (aged 6-8 years old) receive when experiencing difficulties with EF tasks, in addition to an analysis of the developmental factors and cognitive skills that may modulate EF task performance. METHODS: For this study, we use data from a previous randomized active-controlled study (under review), in which forty-six typically developing children aged between 6 and 8 years old (24 girls/22 boys) were enrolled in the training group. The selected children were in the 1st grade (n = 28, x ¯ = 78.32 ± 4.037 months) and 3rd grade of primary education (n = 18, x ¯ = 102.11 ± 3.445). We collected data on EF training performance, compensatory strategies needed and neuropsychological assessments. RESULTS: A total of 80.43% participants required some form of compensatory strategy during training. Regarding required compensatory strategies, those who had lower scores in EF training needed more compensatory strategies, in particular, instructional comprehension (r = -0.561, p < 0.001 for inhibition-tasks; r = -0.342, p < 0.001 for vigilance-tasks). Concerning developmental factors, age significantly predicted better performance in both EF tasks (ß = 0.613, p < 0.001 for inhibition; ß = 0.706, p < 0.001 for attention). As regards task performance, those with better performance in inhibition tasks also had better performance in vigilance tasks (r = 0.72, p < 0.001). Finally, regarding cognitive skills, participants with higher performance in fluid intelligence (Q1, n = 12) had higher scores (U = 14.5, p < 0.05) than the group with the lowest performance (Q4, n = 11) in vigilance. CONCLUSION: As previous literature suggests, inhibition is one of the core processes of EF. Therefore, we should focus training on the core EF processes. Inhibition and vigilance are closely related processes. In terms of the use of compensatory strategies, these are more needed for participants with lower levels of performance in inhibition or vigilance. Regarding strategy analysis, instructional comprehension and self-instruction (goal setting and planning) seem to be the most useful strategies for those with difficulties in inhibitory and vigilance task performance. Regarding development, as expected, age moderates task performance in inhibition and attention. Finally, cognitive skills, such as fluid intelligence and cognitive flexibility, predicted better results in attention. EF training using not only an app, but also compensatory strategies based on user performance, is a new research direction offering more opportunities to generalize EF training in everyday life.

A randomized placebo controlled clinical trial to evaluate the efficacy and safety of minocycline in patients with Angelman syndrome (A-MANECE study).

BACKGROUND: Minocycline is an old tetracycline antibiotic that has shown antiinflammatory and antiapoptotic properties in different neurological disease mouse models. Previous single arm study in humans demonstrated benefits in individuals with Angelman Syndrome (AS); however, its efficacy in patients with Angelman Syndrome has not been assessed in a controlled trial. This was a randomized, double-blind, placebo-controlled, crossover trial in individuals with AS, aged 6 years to 30 years (n = 32, mean age 12 [SD 6·29] years). Participants were randomized to minocycline or placebo for 8 weeks and then switched to the other treatment (a subset of 22 patients) or to receive minocycline for up to 16 weeks (10 patients). After week 16, all patients entered a wash-out 8-week follow-up period. RESULTS: Thirty-six subjects were screened and 34 were randomized. Thirty two subjects (94·1%) completed at least the first period and all of them completed the full trial. Intention-to-treat analysis demonstrated the lack of significantly greater improvements in the primary outcome, mean changes in age equivalent of the development index of the Merrill-Palmer Revised Scale after minocycline compared with placebo (1·90 ± 3·16 and 2·00 ± 3·28, respectively, p = 0·937). Longer treatment duration up to 16 weeks did not result in better treatment outcomes (1·86 ± 3·35 for 8 weeks treatment vs 1·20 ± 5·53 for 16 weeks treatment, p = 0·667). Side effects were not significantly different during minocycline and placebo treatments. No serious adverse events occurred on minocycline. CONCLUSIONS: Minocycline treatment for up to 16 weeks in children and young adults with AS resulted in lack of significant improvements in development indexes compared to placebo treatment. Treatment with minocycline appears safe and well tolerated; even if it cannot be completely ruled out that longer trials might be required for a potential minocycline effect to be expressed, available results and lack of knowledge on the actual mechanism of action do not support this hypothesis. TRIAL REGISTRATION: European Clinical Trial database ( EudraCT 2013-002154-67 ), registered 16th September 2013; US Clinical trials database ( NCT02056665 ), registered 6th February 2014.

Brain Training in Children and Adolescents: Is It Scientifically Valid?

Background: Brain training products are becoming increasingly popular for children and adolescents. Despite the marketing aimed at their use in the general population, these products may provide more benefits for specific neurologically impaired populations. A review of Brain Training (BT) products analyzing their efficacy while considering the methodological limitations of supporting research is required for practical applications. Method: searches were made of the PubMed database (until March 2017) for studies including: (1) empirical data on the use of brain training for children or adolescents and any effects on near transfer (NT) and/or far transfer (FT) and/or neuroplasticity, (2) use of brain training for cognitive training purposes, (3) commercially available training applications, (4) computer-based programs for children developed since the 1990s, and (5) relevant printed and peer-reviewed material. Results: Database searches yielded a total of 16,402 references, of which 70 met the inclusion criteria for the review. We classified programs in terms of neuroplasticity, near and far transfer, and long-term effects and their applied methodology. Regarding efficacy, only 10 studies (14.2%) have been found that support neuroplasticity, and the majority of brain training platforms claimed to be based on such concepts without providing any supporting scientific data. Thirty-six studies (51.4%) have shown far transfer (7 of them are non-independent) and only 11 (15.7%) maintained far transfer at follow-up. Considering the methodology, 40 studies (68.2%) were not randomized and controlled; for those randomized, only 9 studies (12.9%) were double-blind, and only 13 studies (18.6%) included active controls in their trials. Conclusion: Overall, few independent studies have found far transfer and long-term effects. The majority of independent results found only near transfer. There is a lack of double-blind randomized trials which include an active control group as well as a passive control to properly control for contaminant variables. Based on our results, Brain Training Programs as commercially available products are not as effective as first expected or as they promise in their advertisements.

An integrated computer system for teaching Psychology / Un sistema informático integrado para enseñar psicología

PSICO-A is a computer system for teaching Psychology. It is especially indicated for secondary school students and students in first year of a Psychology degree. It is an innovative system as it is the first integrated computational system designed for teaching educational psychology units. PSICO-A integrates various tools and educational influences: it introduces concept maps, free recovery of memory, an effective mechanism of "feedback", simulations and digital games and looks into the student's metacognitive abilities. Its computational architecture is modular and integrates an analyzer that helps the teacher to collect data. We have evaluated this system, confirming a significant improvement in a lot of learning variables

PSICO-A es un sistema informático para la enseñanza de la psicología. Está especialmente indicado para estudiantes de psicología de secundaria y del primer curso del grado. Es un sistema innovador porque es el primer sistema computacional integrado para la enseñanza de unidades didácticas de psicología. PSICO-A integra varias herramientas e influencias educativas, introduce mapas conceptuales, recuperación libre del recuerdo, un mecanismo efectivo de "feedback", simulaciones y juegos digitales e indaga en las capacidades metacognitivas de los estudiantes. Su arquitectura computacional es modular e integra un analizador que ayuda a que el profesor obtenga los datos. Hemos evaluado este sistema, confirmándose una considerable mejora en numerosas variables del aprendizaje

Effect of the theta-beta neurofeedback protocol as a function of subtype in children diagnosed with attention deficit hyperactivity disorder

Neurofeedback is a neuronal self-regulation technique that teaches people to modulate their brain frequencies using visual and auditory reinforcements presented on a computer screen. To assess the effect of neurofeedback training in children with ADHD as far as improved attention and impulse control, and analyze whether or not there are differences between the inattentive and hyperactive subtypes. Fifty children diagnosed with ADHD participated in the study: 14 comprised the control group, and 36 the experimental group (16 with the inattentive ADHD subtype, 20 with the hyperactive ADHD subtype). Attention and impulse control were assessed using the Integrated Visual Auditory CPT (IVA/CPT). Results indicated that the predominantly inattentive group showed significant differences on the Control Scale (p = .023, d = 1.31) and the Attention Scale (p < .01, d = 1.89) of the IVA/CPT; meanwhile the predominantly hyperactive group showed significant improvement on the Control Scale (p = .016, d = 1.21). The control group exhibited no significant differences on either of the two scales (p > .5). In terms of theta/beta ratio, no significant differences were detected (p = .10) between ADHD subtypes. The findings suggest that neurofeedback training using the theta/beta protocol was more effective in the predominantly inattentive subset of individuals with ADHD (AU)

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Characterization of the role of collagen network structure and composition in cancer cell migration.

The geometry of 3D collagen networks is a key factor that influences the behavior of live cells within extra-cellular matrices. This paper presents a method for automatic quantification of the 3D collagen network geometry with fiber resolution in confocal reflection microscopy images. The proposed method is based on a smoothing filter and binarization of the collagen network followed by a fiber reconstruction algorithm. The method is validated on 3D collagen gels with various collagen and Matrigel concentrations. The results reveal that Matrigel affects the collagen network geometry by decreasing the network pore size while preserving the fiber length and fiber persistence length. The influence of network composition and geometry, especially pore size, is preliminarily analyzed by quantifying the migration patterns of lung cancer cells within microfluidic devices filled with three different hydrogel types. The experiments reveal that Matrigel, while decreasing pore size, stimulates cell migration. Further studies on this relationship could be instrumental for the study of cancer metastasis and other biological processes involving cell migration.

Neuronas espejo y teoría de la mente en la explicación de la empatía / Mirror neurons and theory of mind in explaining empathy

La empatía es la capacidad de una persona para vivenciar los pensamientos y sentimientos de los otros, reaccionado adecuadamente. Diferenciamos en la empatía dos componentes; cognitivo y emocional. El componente cognitivo comprende los pensamientos y sentimientos del otro. El componente afectivo comparte el estado emocional de otra persona. Comentamos dos teorías para explicar la empatía: las neuronas espejo y la teoría de la mente. Las neuronas espejo son un tipo particular de neuronas que se activan cuando un individuo realiza una acción, pero también cuando él observa una acción similar realizada por otro individuo Para la teoría de la mente atribuir mente a otro es una actividad pero generamos hipótesis sobre lo que está pensando o sintiendo e interpretamos así su comportamiento. Argumentamos una continuidad genética entre ambas teorías, que se sitúan a nivel explicativo distinto: las neuronas espejo a nivel explicativo distinto: las neuronas espejo a nivel neuronal (neurociencia básica) y la teoría de la mente en el nivel cognitivo. Mostramos implicaciones de ambas teorías en la comprensión del autismo (AU)

Empathy is a person´s ability to experiment other people´s thoughts and feelings and to react to them in an adequate manner. There are two different components within the concept of empathy: cognitive and emotional. The former implies the ability to understand thoughts and feelings of another person; the latter allows the individual to share the mental state of another person responding to his/her demands. We comment here on two theories that explain empathy: the mirror neurons and the Theory of Mind. Mirror neurons are a particular type of neurons which are activated when an individual performs an action, but also when he/she observes a similar action performed by someone else. For theory of mind, to attribute mind to another person is a theoretical activity because we cannot what he/(she is thinking about or feeling, and, in this way, we interpret his/her behavior. We deduce a genetic continuity between both theories in a different explanatory level: mirror neurons at a neuronal level (basic neuroscience) and theory of mind at a cognitive level. Implications of both theories in the explanation of autism are discussed (AU)

[Types of semantic category and stimulus modality in procedural learning: implications for models of semantic memory]. / Tipos de categoría semántica y modalidad de los estímulos en el aprendizaje procedimental: implicaciones sobre los modelos de memoria semántica.

The present work attempts to determine whether procedural learning of a semantic categorisation task is influenced by the type of semantic category of the stimuli (biological and non-biological elements). It is also an attempt to determine the effect of the stimulus presentation modality on the categorisation task. A semantic categorisation task (4 series of 40 stimuli) was administered to 256 participants (128 classifying pictures, and 128 classifying words). Biological categories were responded to faster than non-biological ones although there were no significant differences between the interaction of the category type and the stimulus presentation modality. Reaction times progressively decreased with practice. However, the initial differences disappeared when subjects were trained. The way that current models account for these investigation findings is discussed. In addition, it is suggested that there is an attentional bias in favor of biological elements, which disappears when presumably less relevant elements become more relevant as a function of the task characteristics.

Implementation Intentions and Artificial Agents

We have developed a computer simulation comparing the behavior of two artificial agents (A0 and A1), both of which imitate the use of implementation intentions for achieving a goal R. However, A0 is more balanced for obtaining the goal intention “I intend to achieve R!” while A1 is more balanced for obtaining the implementation intention “I intend to do R when situations L are encountered!”. We have accomplished the statistical analysis (including confidence intervals) and A1 improved the global performance of A0. Our simulation confims partially the relevance of implementions for social cognition in humans (AU)

En este artículo presentamos una simulación por ordenador que busca comparar la conducta de dos agentes artificiales (A0 y A1) que imitan el uso de intenciones de implementación para alcanzar una meta R. Sin embargo, el agente A0 está más inclinado a ejecutar la inten- ción simple “¡Intento alcanzar R!”, mientras que el agente A1 tiene una mayor inclinación a cumplir la intención de implementación “¡Intento alcanzar R cuando voy encontrando las situaciones L!” Hemos tomado como referencia los parámetros introducidos en el estudio meta-analítico más amplio existente sobre el efecto de tales intenciones. Al realizar el análisis estadístico (incluyendo intervalos de confianza), la conclusión ha sido que A1 ha superado a A0 no sólo en la ejecución global sino también en la capacidad para alcanzar R en mayor número de ocasiones. Nuestro estudio confirma parcialmente los resultados acerca de la importancia de las intenciones de implementación en la Psicología Social (AU)

Tipos de categoría semántica y modalidad de los estímulos en el aprendizaje procedimental: implicaciones sobre los modelos de memoria semántica / Types of semantic category and stimulus modality in procedural learning: implications for models of semantic memory

El presente trabajo trata de estudiar si el aprendizaje procedimental de una tarea de categorización semántica puede verse influido por el tipo de categoría al que pertenezcan los estímulos empleados (biológicos o no biológicos). Por otro lado, se pretende describir si existe un efecto de la modalidad de presentación de los estímulos en dicha tarea. Se administró una tarea de categorización semántica (4 series de 40 estímulos) a 256 participantes (128 clasificaban dibujos y 128 palabras). Las categorías biológicas se responden con más rapidez que las categorías no biológicas, aunque no existen diferencias significativas en la interacción del tipo de categoría y la modalidad de presentación de los estímulos. Los tiempos de reacción van disminuyendo progresivamente con la práctica. Sin embargo, las diferencias iniciales desaparecen cuando los sujetos han entrenado. Se discute acerca de cómo los modelos actuales dan cuenta de los hallazgos de esta investigación. Se sugiere, además, que existe una tendencia atencional en los individuos a favor de los elementos biológicos que se atenúa cuando los estímulos presumiblemente menos relevantes para la supervivencia emergen como relevantes en función de lo que se demanda en la tarea (AU)

The present work attempts to determine whether procedural learning of a semantic categorisation task is influenced by the type of semantic category of the stimuli (biological and nonbiological elements). It is also an attempt to determine the effect of the stimulus presentation modality on the categorisation task. A semantic categorisation task (4 series of 40 stimuli) was administered to 256 participants (128 classifying pictures, and 128 classifying words). Biological categories were responded to faster than non-biological ones although there were no significant differences between the interaction of the category type and the stimulus presentation modality. Reaction times progressively decreased with practice. However, the initial differences dissapeared when subjects were trained. The way that current models account for these investigation findings is discussed. In addition, it is suggested that there is an attentional bias in favor of biological elements, which disappears when presumably less relevant elements become more relevant as a function of the task characteristics (AU)