The role of nuclear factor k-B (NF-kB) CYBB gene expression activity of the human NADPH oxidase system

Orientador: Antonio Condino NetoTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias MedicasResumo: Neste trabalho, estudou-se o papel funcional de fator nuclear kappa B (NF-?B), sobre a regulação do gene CYBB e, conseqüentemente, a influência que esse fator exerce sobre o desenvolvimento do sistema NADPH oxidase humano. Células mielocíticas da linhagem U937 transformadas com um vetor carregando o gene repressor de, NF-?B (I-?Ba-S32A/ S36A) demonstraram uma redução na liberação de ânion superóxido e uma diminuição nos níveis de expressão do gene CYBB comparado ao grupo controle de células U937 selvagens. Em paralelo, os mesmos parâmetros foram avaliados em linfócitos B de pacientes com Displasia Anidrótica Ectodérmica com Imunodeficiênca (DAE-ID) transformadas com vírus de Epstein-Barr (EBV), (EBV-DAE-ID?B S32I e DAE-ID NEMO/IKK? X420W), e células de um paciente portador de Doença Granulomatosa Crônica (DGC), com mutação ligada ao X (EBV-DGC-X91°). Esses experimentos também mostraram os mesmos efeitos inibidores da atividade NADPH oxidase, assim como a redução dos níveis de expressão do gene CYBB. Os ensaios de EMSA supershift (anti-p50 humano) demonstraram ausência da ligação do complexo protéico à seqüência consenso para NF-?B 5' do gene do CYBB, confirmando o bloqueio da translocação deste fator para o interior do compartimento nuclear das células U937 transformadas e das células EBV-DAE-ID?B S32I e DAE-ID NEMO/IKK? X420W. Diante destes resultados, conclui-se que o NF-?B é necessário para a ativação da expressão do gene CYBB e conseqüentemente para o desenvolvimento do sistema NADPH oxidase de fagócitos humanos.Abstract: This work investigated the functional role of nuclear factor-? B (NF-?B) in respiratory burst activity and in expression of the human phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase gene CYBB. U937 cells with a stably transfected repressor of NF-?B (I-?Ba-S32A/ S36A) demonstrated significantly lower superoxide release and lower CYBB gene expression compared with control U937 cells. We further tested Epstein-Barr virus (EBV)-transformed B cells from patients with anhidrotic ectodermal dysplasia with immunodeficiency (EDAID), an inherited disorder of NF-?B function (DAE-IDI?B S32I e DAE-ID NEMO/IKK? X420W). Superoxide release and CYBB gene expression by EDA-ID cells were significantly decreased compared with healthy cells and similar to cells from patients with X-linked chronic granulomatous disease (X91° CGD). Gel shift assays demonstrated loss of recombinant human p50 binding to a NF-?B site 5' to the CYBB gene inU937 cells treated with NF-?B inhibitors, repressor-transfected U937 cells, and EDA-ID patients' cells. These studies show that NF-?B is necessary for CYBB gene expression and activation of the phagocyte NADPH oxidase in this model system.DoutoradoDoutor em Farmacologi

CB2 cannabinoid receptor expression is increased in 129S1/SvImJ mice: behavioral consequences.

Genetic and environmental factors are implicated in the etiology of neuropsychiatric diseases. Inbred mouse strains, including the 129S1/SvImJ (S1), constitute important models to study the influence of genetic factors in these conditions. S1 mice displayed anxiogenic-like behavior, impaired fear extinction, and increased prepulse inhibition (PPI) of startle reflex compared to C57BL/6J (BL6) mice. Given the role played by the endocannabinoid system (ECS) in these responses, we evaluated the expression of the ECS components in different brain regions in S1 mice. Gene expression levels of the cannabinoid type-1 and type-2 receptors (CB1R and CB2R) and the endocannabinoid metabolizing enzymes varied depending on the brain region evaluated. Notably, CB2R expression markedly increased in the amygdala, prefrontal cortex and hippocampus in S1 mice. Moreover, CB2R blockade with SR144528 partially rescued the anxiogenic phenotype in S1 mice, while CB2R activation with JWH133 potentiated the deficits in fear extinction and the PPI of startle reflex in this mouse strain. These data suggest that CB2R is involved in the behavioral alterations observed in S1 mice and underline the importance of this cannabinoid receptor subtype in the regulation of certain central nervous system disorders.post-print1604 K

Adolescent exposure to the Spice/K2 cannabinoid JWH-018 impairs sensorimotor gating and alters cortical perineuronal nets in a sex-dependent manner.

The consumption of synthetic cannabinoids during adolescence is reported to be a risk factor for the appearance of psychiatric disorders later in life. JWH-018 was identified as one of the primary psychoactive components present in Spice/K2 preparations. This study evaluated the short- and long-term consequences of exposure to JWH-018 during the adolescence in anxiety-like behavior, fear extinction, and sensorimotor gating in male and female mice. Alterations in anxiety varied depending on the time interval between treatment and behavioral analysis along with sex, while no changes were observed in the extinction of fear memory. A decrease in prepulse inhibition of the startle reflex was revealed in male, but not female, mice at short- and long-term. This behavioral disturbance was associated with a reduction in the number of perineuronal nets in the prelimbic and infralimbic regions of the prefrontal cortex in the short-term. Furthermore, adolescent exposure to JWH-018 induced an activation of microglia and astrocytes in the prefrontal cortex of male mice at both time intervals. A transitory decrease in the expression of GAD67 and CB2 cannabinoid receptors in the prefrontal cortex was also found in male mice exposed to JWH-018. These data reveal that the treatment with JWH-018 during the adolescence leads to long-lasting neurobiological changes related to psychotic-like symptoms, which were sex-dependent.post-print2490 K

Strike (with) a Pose: Neural Networks Are Easily Fooled by Strange Poses of Familiar Objects

Despite excellent performance on stationary test sets, deep neural networks (DNNs) can fail to generalize to out-of-distribution (OoD) inputs, including natural, non-adversarial ones, which are common in real-world settings. In this paper, we present a framework for discovering DNN failures that harnesses 3D renderers and 3D models. That is, we estimate the parameters of a 3D renderer that cause a target DNN to misbehave in response to the rendered image. Using our framework and a self-assembled dataset of 3D objects, we investigate the vulnerability of DNNs to OoD poses of well-known objects in ImageNet. For objects that are readily recognized by DNNs in their canonical poses, DNNs incorrectly classify 97% of their pose space. In addition, DNNs are highly sensitive to slight pose perturbations. Importantly, adversarial poses transfer across models and datasets. We find that 99.9% and 99.4% of the poses misclassified by Inception-v3 also transfer to the AlexNet and ResNet-50 image classifiers trained on the same ImageNet dataset, respectively, and 75.5% transfer to the YOLOv3 object detector trained on MS COCO.Comment: Poster at the 2019 Conference on Computer Vision and Pattern Recognitio

Adaptando espacios, conectando gente

Comunicación presentada en las I Jornadas de Bibliotecas G9 sobre buenas prácticas en atención a espacios y usuarios, organizada por el Servicio de Bibliotecas de la UEx en Jarandilla de la Vera (Cáceres) los días 29 y 30 de septiembre de 2016Comunicación que muestra las acciones de la Biblioteca de la Universidad de Castilla-La Mancha para mejorar los espacios bibliotecarios y promover el silencio en el estudio.Communication showing the actions of the Library of the University of Castilla-La Mancha to improve library spaces and promote the silence in the study

Associations betweenWeight Status and Situational Motivation toward Fitness Testing in Physical Education: The Mediator Role of Physical Fitness

Background: This article examines the differences in situational motivation toward fitness testing in physical education classes between non-overweight and overweight students, as well as the mediator effect of objective and perceived physical fitness on the relationship between weight status and motivation toward fitness testing. Methods: A total of 534 adolescents (298 boys, 55.80%) participated in the study. Perceived physical fitness and situational motivation toward fitness testing were measured through questionnaires, whereas weight status and physical fitness were objectively measured. Results: Overweight students had lower intrinsic motivation (p< 0.001), and higher external regulation (p< 0.01) and amotivation (p< 0.05) during fitness testing in a physical education class than their non-overweight peers. The influence of being overweight on motivation regulations toward fitness testing was mediated by objective physical fitness level for intrinsic motivation (B= -0.140), external regulation (B= 0.104) and amotivation (B= 0.146). Perceived physical fitness was also used as a second mediator between weight status and intrinsic motivation (B= -0.117). Conclusions: Strategies to improve objective and perceived physical fitness in overweight students are necessary to increase self-determined motivation during fitness testing in physical education lesson

ADAPTANDO ESPACIOS, CONECTANDO GENTE: LA EXPERIENCIA REALIZADA EN LA BIBLIOTECA GENERAL DEL CAMPUS DE CUENCA

La incorporación de las Universidades al Espacio Europeo de Educación Superior ha supuesto para las bibliotecas universitarias la necesidad de adaptar sus espacios a las exigencias del nuevo modelo educativo. En este mismo contexto, la crisis vivida en los últimos años ha generado un estancamiento en inversiones que ha obligado a transformar los espacios con pocos recursos.En este artículo os presentamos los cambios que hemos ido introduciendo en el edificio de la Biblioteca General del Campus de Cuenca para responder a las nuevas necesidades de nuestros usuarios, adaptando o reinventando espacios con esfuerzo e imaginación, que nunca pueden faltar en los tiempos de crisis, procurando siempre que la Biblioteca sea el punto de encuentro de la vida académica y universitaria. The incorporation of universities into the European Higher Education Area has impressed upon University libraries, the necessity of adapting spaces to the demands of a new educational model. In this context, the crisis of the last few years has lead to a standstill in investments. This has meant traditional areas have had to be transformed with few resources. In this article we have tried to show the work that Cuenca campus university library has been doing to adapt its areas. A few examples are: using corridors for exhibition areas, leisure and relaxation zones, reading corners and storage areas transformed into working group areas.

Diseño y validación de una escala para medir en profesores de Educación Física el uso responsable de las pruebas de condición física (FITPET)

Objective: The aim of this study was to design and validate a scale that would allow the evaluation in Physical Education teachers the responsible use of physical fitness tests related to health. Method: The sample was composed of 374 secondary school teachers (266 men and 108 women), from educational centers belonging to the eight Andalusian provinces, aged between 24 and 67 years (41.92 ± 9.24). Results: Firstly, a 26-item instrument was designed, which obtained item-total correlation values of ≥ .35, except for 5 items. Then, the internal structure of the scale was evaluated and proved to be relevant. The statistical analysis of the items and the subsequent exploratory factor analysis resulted in five factors (orientation of the result, use of participatory styles, the educational approach, methodological rigor, and positive reinforcement), with positive and significant correlations, confirmed by confirmatory factor analysis, factor invariance tests, as well as reliability and convergent and discriminant validity and reliability. The results of the analysis of psychometric properties of the scale were moderate and allowed us to offer a valid and reliable 15-item an ad hoc instrument, with adequate values of validity and reliability, proving its usefulness the evaluation in Physical Education teachers the responsible use of physical fitness tests in their classesObjetivo: el presente estudio tuvo como objetivo di-señar y validar una escala para evaluar en profesores de Educación Física el uso responsable de las pruebas de condición física relacionadas con la salud. Método: participaron un total de 374 docentes de secundaria (266 hombres y 108 mujeres) de centros educativos per-tenecientes a las ocho provincias andaluzas, con edades comprendidas entre 24 y 67 años (41.92 ± 9.24 años). Resultados: en primer lugar, se diseñó un instrumento de 26 ítems, que obtuvo valores de correlación ítem-total ≥ .35, exceptuando 5 ítems. Posteriormente, se evaluó la estructura interna de la escala, resultando esta pertinente. El análisis estadístico de los ítems y el pos-terior análisis factorial exploratorio dio como resultado cinco factores (orientación del resultado, uso de estilos participativos, el enfoque educativo, rigor metodoló-gico y refuerzo positivo), con correlaciones positivas y significativas, constatadas mediante análisis factorial confirmatorio, pruebas de invarianza factorial, así como de fiabilidad y validez convergente y discriminante. Los resultados del análisis de propiedades psicométricas de la escala fueron adecuados y permitieron ofrecer un ins-trumento ad hoc de 15 ítems, con moderados valores de validez y fiabilidad, acreditando su utilidad para valorar en profesores de Educación Física el uso responsable de las pruebas de condición física en sus clases.Actividad Física y Deport

Destete precoz de los terneros en explotaciones de vacuno de carne: consecuencias sobre los rendimentos técnico-económicos del rebaño

Unpublishe

Design and validation of a scale to assess the responsible use of fitness testing in physical education teachers (FITPET)

Objetivo: el presente estudio tuvo como objetivo diseñar y validar una escala para evaluar en profesores de Educación Física el uso responsable de las pruebas de condición física relacionadas con la salud. Método: participaron un total de 374 docentes de secundaria (266 hombres y 108 mujeres) de centros educativos pertenecientes a las ocho provincias andaluzas, con edades comprendidas entre 24 y 67 años (41.92 ± 9.24 años). Resultados: en primer lugar, se diseñó un instrumento de 26 ítems, que obtuvo valores de correlación ítemtotal ≥ .35, exceptuando 5 ítems. Posteriormente, se evaluó la estructura interna de la escala, resultando esta pertinente. El análisis estadístico de los ítems y el posterior análisis factorial exploratorio dio como resultado cinco factores (orientación del resultado, uso de estilos participativos, el enfoque educativo, rigor metodoló- gico y refuerzo positivo), con correlaciones positivas y significativas, constatadas mediante análisis factorial confirmatorio, pruebas de invarianza factorial, así como de fiabilidad y validez convergente y discriminante. Los resultados del análisis de propiedades psicométricas de la escala fueron adecuados y permitieron ofrecer un instrumento ad hoc de 15 ítems, con moderados valores de validez y fiabilidad, acreditando su utilidad para valorar en profesores de Educación Física el uso responsable de las pruebas de condición física en sus clases.Objective: The aim of this study was to design and validate a scale that would allow the evaluation in Physical Education teachers the responsible use of physical fitness tests related to health. Method: The sample was composed of 374 secondary school teachers (266 men and 108 women), from educational centers belonging to the eight Andalusian provinces, aged between 24 and 67 years (41.92 ± 9.24). Results: Firstly, a 26-item instrument was designed, which obtained item-total correlation values of ≥ .35, except for 5 items. Then, the internal structure of the scale was evaluated and proved to be relevant. The statistical analysis of the items and the subsequent exploratory factor analysis resulted in five factors (orientation of the result, use of participatory styles, the educational approach, methodological rigor, and positive reinforcement), with positive and significant correlations, confirmed by confirmatory factor analysis, factor invariance tests, as well as reliability and convergent and discriminant validity and reliability. The results of the analysis of psychometric properties of the scale were moderate and allowed us to offer a valid and reliable 15-item an ad hoc instrument, with adequate values of validity and reliability, proving its usefulness the evaluation in Physical Education teachers the responsible use of physical fitness tests in their classes