Methylglyoxal Produced by Amyloid- Peptide-Induced Nitrotyrosination of Triosephosphate Isomerase Triggers Neuronal Death in Alzheimer’s Disease

Amyloid-β peptide (Aβ) aggregates induce nitro-oxidative stress, contributing to the characteristic neurodegeneration found in Alzheimer's disease (AD). One of the most strongly nitrotyrosinated proteins in AD is the triosephosphate isomerase (TPI) enzyme which regulates glycolytic flow, and its efficiency decreased when it is nitrotyrosinated. The main aims of this study were to analyze the impact of TPI nitrotyrosination on cell viability and to identify the mechanism behind this effect. In human neuroblastoma cells (SH-SY5Y), we evaluated the effects of Aβ42 oligomers on TPI nitrotyrosination. We found an increased production of methylglyoxal (MG), a toxic byproduct of the inefficient nitro-TPI function. The proapoptotic effects of Aβ42 oligomers, such as decreasing the protective Bcl2 and increasing the proapoptotic caspase-3 and Bax, were prevented with a MG chelator. Moreover, we used a double mutant TPI (Y165F and Y209F) to mimic nitrosative modifications due to Aβ action. Neuroblastoma cells transfected with the double mutant TPI consistently triggered MG production and a decrease in cell viability due to apoptotic mechanisms. Our data show for the first time that MG is playing a key role in the neuronal death induced by Aβ oligomers. This occurs because of TPI nitrotyrosination, which affects both tyrosines associated with the catalytic center.

Risk Prediction Scores for Recurrence and Progression of Non-Muscle Invasive Bladder Cancer: An International Validation in Primary Tumours

Abstract Objective: We aimed to determine the validity of two risk scores for patients with non-muscle invasive bladder cancer in different European settings, in patients with primary tumours. Methods: We included 1,892 patients with primary stage Ta or T1 non-muscle invasive bladder cancer who underwent a transurethral resection in Spain (n = 973), the Netherlands (n = 639), or Denmark (n = 280). We evaluated recurrence-free survival and progression-free survival according to the European Organisation for Research and Treatment of Cancer (EORTC) and the Spanish Urological Club for Oncological Treatment (CUETO) risk scores for each patient and used the concordance index (c-index) to indicate discriminative ability. Results: The 3 cohorts were comparable according to age and sex, but patients from Denmark had a larger proportion of patients with the high stage and grade at diagnosis (p,0.01). At least one recurrence occurred in 839 (44%) patients and 258 (14%) patients had a progression during a median follow-up of 74 months. Patients from Denmark had the highest 10- year recurrence and progression rates (75% and 24%, respectively), whereas patients from Spain had the lowest rates (34% and 10%, respectively). The EORTC and CUETO risk scores both predicted progression better than recurrence with c-indices ranging from 0.72 to 0.82 while for recurrence, those ranged from 0.55 to 0.61. Conclusion: The EORTC and CUETO risk scores can reasonably predict progression, while prediction of recurrence is more difficult. New prognostic markers are needed to better predict recurrence of tumours in primary non-muscle invasive bladder cancer patients.

Evaluating the impact of filming on the number of errors committed by nursing students to determine the efficacy of simulated clinical situations

Clinic simulation as a training and knowledge method allows people experiment a real event representation with the aim of acquiring knowledge, abilities and aptitudes. The filming of the staging represents a useful tool to review the decisions taken and the actions they did, with the purpose to highlight the strengths, weaknesses and the areas for improvement. The article describes a study carried out by a group of students in second course of nursing, and it tries to evaluate if there is any influence if somebody is filming you during the clinic simulation, does it make you do more errors or not?

Anti-MPER antibodies with heterogeneous neutralization capacity are detectable in most untreated HIV-1 infected individuals

Background The MPER region of the HIV-1 envelope glycoprotein gp41 is targeted by broadly neutralizing antibodies. However, the localization of this epitope in a hydrophobic environment seems to hamper the elicitation of these antibodies in HIV infected individuals. We have quantified and characterized anti-MPER antibodies by ELISA and by flow cytometry using a collection of mini gp41-derived proteins expressed on the surface of 293T cells. Longitudinal plasma samples from 35 HIV-1 infected individuals were assayed for MPER recognition and MPER-dependent neutralizing capacity using HIV-2 viruses engrafted with HIV-1 MPER sequences. Results Miniproteins devoid of the cysteine loop of gp41 exposed the MPER on 293T cell membrane. Anti-MPER antibodies were identified in most individuals and were stable when analyzed in longitudinal samples. The magnitude of the responses was strongly correlated with the global response to the HIV-1 envelope glycoprotein, suggesting no specific limitation for anti-MPER antibodies. Peptide mapping showed poor recognition of the C-terminal MPER moiety and a wide presence of antibodies against the 2F5 epitope. However, antibody titers failed to correlate with 2F5-blocking activity and, more importantly, with the specific neutralization of HIV-2 chimeric viruses bearing the HIV-1 MPER sequence; suggesting a strong functional heterogeneity in anti-MPER humoral responses. Conclusions Anti-MPER antibodies can be detected in the vast majority of HIV-1 infected individuals and are generated in the context of the global anti-Env response. However, the neutralizing capacity is heterogeneous suggesting that eliciting neutralizing anti-MPER antibodies by immunization might require refinement of immunogens to skip nonneutralizing responses.

Prevalence of Ischemic Heart Disease and Management of Coronary Risk in Daily Clinical Practice: Results from a Mediterranean Cohort of HIV-Infected Patients

There are conflicting data on the prevalence of coronary events and the quality of the management of modifiable cardiovascular risk factors (CVRF) inHIV-infected patients. Methods.We performed a retrospective descriptive study to determine the prevalence of coronary events and to evaluate the management of CVRF in a Mediterranean cohort of 3760 HIV-1-infected patients from April 1983 through June 2011. Results.We identified 81 patients with a history of a coronary event (prevalence 2.15%); 83% of them suffered an acute myocardial infarction. At the time of the coronary event, CVRF were highly prevalent (60.5% hypertension, 48% dyslipidemia, and 16% diabetes mellitus).OtherCVRF, such as smoking, hypertension, lack of exercise, and body mass index, were not routinely assessed. After the coronary event, a significant decrease in total cholesterol ( � = 0.025) and LDLcholesterol ( � = 0.004) was observed. However, the percentage of patients whomaintained LDL-cholesterol > 100mg/dL remained stable (from 46% to 41%, � = 0.103). Patients using protease inhibitors associated with a favorable lipid profile increased over time ( � = 0.028). Conclusions.The prevalence of coronary events in our cohort is low. CVRF prevalence is high and theirmanagement is far from optimal. More aggressive interventions should be implemented to diminish cardiovascular risk in HIV-infected patients.

Acercamiento a las características de los videojuegos y sus beneficios en el aprendizaje

En este artículo se presenta una aproximación hacia algunas de las características implícitas en los videojuegos que pueden ayudar a desarrollar beneficios en los procesos de aprendizaje: reglas, metas y objetivos, narrativa y fantasía. Mediante la explicación de estas características, surgen ejemplos de las diferentes situaciones en las que el jugador se ve inmerso y que generaran un proceso de cambio en el comportamiento de la persona.

Juegos digitales y alfabetización digital: Entrevistas con profesores de primaria que utilizan juegos en la práctica Educativa

A diferencia de otros medios como la televisión o el cine, los juegos digitales se presentan como un medio único y diferente que proporcionan una nueva forma de retórica persuasiva. En este trabajo, se presentan los casos de 2 profesoras de primaria que utilizan juegos digitales en la práctica educativa. Los casos se encuentran dentro de un marco de multimodalidad que muestran la posición del docente en la educación. Se exploran los desafíos que enfrentan los docentes como instructores y la aplicación de juegos digitales en el aula moderna. Desde una perspectiva etnográfica, se han utilizado técnicas de recogida de información, como el análisis documental y la entrevista para obtener datos sobre cada uno de los casos. Los resultados obtenidos forman parte de un trabajo más amplio, pero aquí solo se muestran 2 casos, que plantean cuestiones como cuál es la posición de los profesores con respecto al uso de juegos digitales en las aulas, qué impulsa a los profesores a utilizarlos y qué tipo de apoyo o recursos necesitan los profesores. Las conclusiones de este trabajo nos llevan a entender el porque de su uso en las aulas, permiten a los estudiantes aprender y estar motivados, ante el uso de juegos en l apráctica educative, los estudiantes se encuentran con experiencias que estimulan y les provocan una conexión personal.

Aprendizagem baseada em Jogos Digitais Entrevistas com professores que utilizam jogos digitais em suas práticas educativas

In contrast to other media like TV or cinema, digital games are unique and different because they offer a persuasive rhetoric. This investigation introduces the cases of two primary school teachers who use digital games as one of their teaching methods. Both cases are multimodal and show the teacher’s position in education. This work also explores the challenges faced by teachers as instructors, and the application of digital games in modern classes.From an ethnographic view, gathering information techniques are used, such as documentary analysis and interviews in order to collect data about each case with two teachers from the province of Barcelona. The obtained results raise important questions: what is the main role of a teacher using digital games in class, how teachers participate in learning based on digital games and how digital games are developed and combined with other teaching methodologies. The conclusions obtained by this research let us understand the reason why using digital games in class allows the students to learn and keep their motivation: digital games stimulate them so they can establish a personal connection.

Algoritmos interactivos para la separación de fuentes y deconvolución de canal mediante Java

El objetivo de estos programas es crear una herramienta que nos permita, de una manera fácil, entender mejor la separación de fuentes y la deconvolución de canal . Por eso se presenta el diseño, mediante Java, de una página web [1]: http//www.uvic.es/projectes/SeparationSources con carácter marcadamente didáctico para el estudio y evaluación de diferentes algoritmos propuestos en la bibliografía.

Source separation techniques applied to linear prediction

The prediction filters are well known models for signal estimation, in communications, control and many others areas. The classical method for deriving linear prediction coding (LPC) filters is often based on the minimization of a mean square error (MSE). Consequently, second order statistics are only required, but the estimation is only optimal if the residue is independent and identically distributed (iid) Gaussian. In this paper, we derive the ML estimate of the prediction filter. Relationships with robust estimation of auto-regressive (AR) processes, with blind deconvolution and with source separation based on mutual information minimization are then detailed. The algorithm, based on the minimization of a high-order statistics criterion, uses on-line estimation of the residue statistics. Experimental results emphasize on the interest of this approach.

Simulated Annealing, High-Order Statistics and Mutual Information for Separation of Sources

In this article, the fusion of a stochastic metaheuristic as Simulated Annealing (SA) with classical criteria for convergence of Blind Separation of Sources (BSS), is shown. Although the topic of BSS, by means of various techniques, including ICA, PCA, and neural networks, has been amply discussed in the literature, to date the possibility of using simulated annealing algorithms has not been seriously explored. From experimental results, this paper demonstrates the possible benefits offered by SA in combination with high order statistical and mutual information criteria for BSS, such as robustness against local minima and a high degree of flexibility in the energy function.

Blind Inversion of Wiener System using a minimization-projection (MP) approach

In this paper, a new algorithm for blind inversion of Wiener systems is presented. The algorithm is based on minimization of mutual information of the output samples. This minimization is done through a Minimization-Projection (MP) approach, using a nonparametric “gradient” of mutual information.

A Gradient based algorithm for blind inversion of Wiener System using multi-variate score functions

A Wiener system is a linear time-invariant filter, followed by an invertible nonlinear distortion. Assuming that the input signal is an independent and identically distributed (iid) sequence, we propose an algorithm for estimating the input signal only by observing the output of the Wiener system. The algorithm is based on minimizing the mutual information of the output samples, by means of a steepest descent gradient approach.