bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteome Analysis and Functional Expression Identify Mortalin as an Antiapoptotic Gene Induced by Elevation of [Na
+
]
i
/[K
+
]
i
Ratio in Cultured Vascular Smooth Muscle Cells
Authors: Taurin Sebastien , Seyrantepe Volkan , Orlov Sergei N. , Tremblay Tammy-Lynn , Thibault Pierre , Bennett Martin R. , Hamet Pavel , Pshezhetsky Alexey V.
Published: November 2002

Apoptosis of vascular smooth muscle cells (VSMCs) plays an important role in remodeling of vessel walls, one of the major determinants of long-term blood pressure elevation and an independent risk factor for cardiovascular morbidity and mortality. Recently, we have found that apoptosis in cultured VSMCs can be inhibited by inversion of the intracellular [Na
+
]/[K
+
] ratio after the sustained blockage of the Na
+
,K
+
-ATPase by ouabain. To understand the mechanism of ouabain action, we analyzed subsets of hydrophilic and hydrophobic VSMC proteins from control and ouabain-treated cells by 2-dimensional electrophoresis. Ouabain treatment led to overexpression of numerous soluble and hydrophobic cellular proteins. Among proteins that showed the highest level of ouabain-induced expression, we identified mortalin (also known as GRP75 or PBP-74), a member of the heat shock protein 70 (HSP70) superfamily and a marker for cellular mortal and immortal phenotypes. Northern and Western blotting and immunocytochemistry all have confirmed that treatment of VSMCs with ouabain results in potent induction of mortalin expression. Transient transfection of cells with mortalin cDNA led to at least a 6-hour delay in the development of apoptosis after serum deprivation. The expression of tumor suppressor gene, p53, in mortalin-transfected cells was delayed to the same extent, and the expressed protein showed abnormal perinuclear distribution, suggesting that p53 is retained and inactivated by mortalin. Our studies therefore define a new [Na
+
]
i
/[K
+
]
i
-responsive signaling pathway that may play an important role in the regulation of programmed cell death in VSMCs.
Increased Superoxide and Vascular Dysfunction in CuZnSOD-Deficient Mice
Authors: Didion Sean P. , Ryan Michael J. , Didion Lisa A. , Fegan Pamela E. , Sigmund Curt D. , Faraci Frank M.
Published: November 2002

Increased superoxide is thought to play a major role in vascular dysfunction in a variety of disease states. Superoxide dismutase (SOD) limits increases in superoxide; however, the functional significance of selected isoforms of SOD within the vessel wall are unknown. We tested the hypothesis that selective loss of CuZnSOD results in increased superoxide and altered vascular responsiveness in CuZnSOD-deficient (CuZnSOD
−/−
) mice compared with wild-type (CuZnSOD
+/+
) littermates. Total SOD activity was reduced (
P
<0.05) by approximately 60% and CuZnSOD protein was absent in aorta from CuZnSOD
−/−
as compared with wild-type mice. Vascular superoxide levels, measured using lucigenin (5 μmol/L)-enhanced chemiluminescence and hydroethidine (2 μmol/L)-based confocal microscopy, were increased (approximately 2-fold;
P
<0.05) in CuZnSOD
−/−
mice as compared with wild-type mice. Relaxation of the carotid artery in response to acetylcholine and authentic nitric oxide was impaired (
P
<0.05) in CuZnSOD
−/−
mice. For example, maximal relaxation to acetylcholine (100 μmol/L) was 50±6% and 69±5% in CuZnSOD
−/−
and wild-type mice, respectively. Contractile responses of the carotid artery were enhanced (
P
<0.05) in CuZnSOD
−/−
mice in response to phenylephrine and serotonin, but not to potassium chloride or U46619. In vivo, dilatation of cerebral arterioles (baseline diameter=31±1 μm) to acetylcholine was reduced by approximately 50% in CuZnSOD
−/−
mice as compared with wild-type mice (
P
<0.05). These findings provide the first direct insight into the functional importance of CuZnSOD in blood vessels and indicate that this specific isoform of SOD limits increases in superoxide under basal conditions. CuZnSOD-deficiency results in altered responsiveness in both large arteries and microvessels.
Fibroblast Growth Factor-2 Gene Transfer Can Stimulate Hepatocyte Growth Factor Expression Irrespective of Hypoxia-Mediated Downregulation in Ischemic Limbs
Authors: Onimaru Mitsuho , Yonemitsu Yoshikazu , Tanii Mitsugu , Nakagawa Kazunori , Masaki Ichiro , Okano Shinji , Ishibashi Hiroaki , Shirasuna Kanemitsu , Hasegawa Mamoru , Sueishi Katsuo
Published: November 2002

Hepatocyte growth factor (HGF) is a potent angiogenic polypeptide that stimulates angiogenesis. Transcriptional regulation of HGF, however, has not been fully defined, with the exception of the hypoxia-mediated downregulation in cultured cells. In the present study, we report that angiogenic growth factors, including HGF, were upregulated in a murine model of critical limb ischemia in vivo, a finding that was in conflict with previous in vitro data. Mice deficient in basic fibroblast growth factor-2 (FGF-2) showed reduced induction of HGF protein in ischemic muscles, and overexpression of FGF-2 via gene transfer stimulated endogenous HGF, irrespective of the presence of ischemia. In culture, FGF-2 rapidly stimulated HGF mRNA, and a sustained expression was evident in the time course in vascular smooth muscle cells and fibroblasts. FGF-2–mediated induction of HGF was fully dependent on the mitogen-activated protein kinase pathway yet was not affected by either hypoxia or a protein kinase A inhibitor. In the early expression, FGF-2 directly stimulated HGF mRNA without the requirement of new protein synthesis, whereas sustained induction of HGF in the later phase was partly mediated by platelet-derived growth factor-AA. Furthermore, in vivo overexpression of FGF-2 significantly improved the blood perfusion, and the effect was abolished by systemic blockade of HGF in ischemic limbs. This is the first demonstration of a regulational mechanism of HGF expression via FGF-2 that was independent of the presence of hypoxia. The harmonized therapeutic effects of FGF-2, accompanied with the activity of endogenous HGF, may provide a beneficial effect for the treatment of limb ischemia.
Gα
12/13
Mediates α
1
-Adrenergic Receptor–Induced Cardiac Hypertrophy
Authors: Maruyama Yoshiko , Nishida Motohiro , Sugimoto Yoshiyuki , Tanabe Shihori , Turner Justin H. , Kozasa Tohru , Wada Teiji , Nagao Taku , Kurose Hitoshi
Published: November 2002

In neonatal cardiomyocytes, activation of the G
q
-coupled α
1
-adrenergic receptor (α
1
AR) induces hypertrophy by activating mitogen-activated protein kinases, including c-Jun NH
2
-terminal kinase (JNK). Here, we show that JNK activation is essential for α
1
AR-induced hypertrophy, in that α
1
AR-induced hypertrophic responses, such as reorganization of the actin cytoskeleton and increased protein synthesis, could be blocked by expressing the JNK-binding domain of JNK-interacting protein-1, a specific inhibitor of JNK. We also identified the classes and subunits of G proteins that mediate α
1
AR-induced JNK activation and hypertrophic responses by generating several recombinant adenoviruses that express polypeptides capable of inhibiting the function of specific G-protein subunits. α
1
AR-induced JNK activation was inhibited by the expression of carboxyl terminal regions of Gα
q
, Gα
12
, and Gα
13
. JNK activation was also inhibited by the Gα
q/11
- or Gα
12/13
-specific regulator of G-protein signaling (RGS) domains and by C3 toxin but was not affected by treatment with pertussis toxin or by expression of the carboxyl terminal region of G protein–coupled receptor kinase 2, a polypeptide that sequesters Gβγ. α
1
AR-induced hypertrophic responses were inhibited by Gα
q/11
- and Gα
12/13
-specific RGS domains, C3 toxin, and the carboxyl terminal region of G protein–coupled receptor kinase 2 but not by pertussis toxin. Activation of Rho was inhibited by carboxyl terminal regions of Gα
12
and Gα
13
but not by Gα
q
. Our findings suggest that α
1
AR-induced hypertrophic responses are mediated in part by a Gα
12/13
-Rho-JNK pathway, in part by a G
q/11
-JNK pathway that is Rho independent, and in part by a Gβγ pathway that is JNK independent.
Real-Time Computing Without Stable States: A New Framework for Neural Computation Based on Perturbations
Authors: Maass Wolfgang , Natschläger Thomas , Markram Henry
Published: November 2002

A key challenge for neural modeling is to explain how a continuous stream of multimodal input from a rapidly changing environment can be processed by stereotypical recurrent circuits of integrate-and-fire neurons in real time. We propose a new computational model for real-time computing on time-varying input that provides an alternative to paradigms based on Turing machines or attractor neural networks. It does not require a task-dependent construction of neural circuits. Instead, it is based on principles of high-dimensional dynamical systems in combination with statistical learning theory and can be implemented on generic evolved or found recurrent circuitry. It is shown that the inherent transient dynamics of the high-dimensional dynamical system formed by a sufficiently large and heterogeneous neural circuit may serve as universal analog fading memory. Readout neurons can learn to extract in real time from the current state of such recurrent neural circuit information about current and past inputs that may be needed for diverse tasks. Stable internal states are not required for giving a stable output, since transient internal states can be transformed by readout neurons into stable target outputs due to the high dimensionality of the dynamical system. Our approach is based on a rigorous computational model, the liquid state machine, that, unlike Turing machines, does not require sequential transitions between well-defined discrete internal states. It is supported, as the Turing machine is, by rigorous mathematical results that predict universal computational power under idealized conditions, but for the biologically more realistic scenario of real-time processing of time-varying inputs. Our approach provides new perspectives for the interpretation of neural coding, the design of experiments and data analysis in neurophysiology, and the solution of problems in robotics and neurotechnology.
Universal Approximation of Multiple Nonlinear Operators by Neural Networks
Authors: Back Andrew D. , Chen Tianping
Published: November 2002

Recently, there has been interest in the observed capabilities of some classes of neural networks with fixed weights to model multiple nonlinear dynamical systems. While this property has been observed in simulations, open questions exist as to how this property can arise. In this article, we propose a theory that provides a possible mechanism by which this multiple modeling phenomenon can occur.
Invariant Object Recognition in the Visual System with Novel Views of 3D Objects
Authors: Stringer Simon M. , Rolls Edmund T.
Published: November 2002

To form view-invariant representations of objects, neurons in the inferior temporal cortex may associate together different views of an object, which tend to occur close together in time under natural viewing conditions. This can be achieved in neuronal network models of this process by using an associative learning rule with a short-term temporal memory trace. It is postulated that within a view, neurons learn representations that enable them to generalize within variations of that view. When three-dimensional (3D) objects are rotated within small angles (up to, e.g., 30 degrees), their surface features undergo geometric distortion due to the change of perspective. In this article, we show how trace learning could solve the problem of in-depth rotation-invariant object recognition by developing representations of the transforms that features undergo when they are on the surfaces of 3D objects. Moreover, we show that having learned how features on 3D objects transform geometrically as the object is rotated in depth, the network can correctly recognize novel 3D variations within a generic view of an object composed of a new combination of previously learned features. These results are demonstrated in simulations of a hierarchical network model (VisNet) of the visual system that show that it can develop representations useful for the recognition of 3D objects by forming perspective-invariant representations to allow generalization within a generic view.
Dynamical Working Memory and Timed Responses: The Role of Reverberating Loops in the Olivo-Cerebellar System
Authors: Kistler Werner M. , Zeeuw Chris I. De
Published: November 2002

This article explores dynamical properties of the olivo-cerebellar system that arise from the specific wiring of inferior olive (IO), cerebellar cortex, and deep cerebellar nuclei (DCN). We show that the irregularity observed in the firing pattern of the IO neurons is not necessarily produced by noise but can instead be the result of a purely deterministic network effect. We propose that this effect can serve as a dynamical working memory or as a neuronal clock with a characteristic timescale of about 100 ms that is determined by the slow calcium dynamics of IO and DCN neurons. This concept provides a novel explanation of how the cerebellum can solve timing tasks on a timescale that is two orders of magnitude longer than the millisecond timescale usually attributed to neuronal dynamics.

One of the key ingredients of our model is the observation that due to postinhibitory rebound, DCN neurons can be driven by GABAergic (“inhibitory”) input from cerebellar Purkinje cells. Topographic projections from the DCN to the IO form a closed reverberating loop with an overall synaptic transmission delay of about 100 ms that is in resonance with the intrinsic oscillatory properties of the inferior olive.

We use a simple time-discrete model based on McCulloch-Pitts neurons in order to investigate in a first step some of the fundamental properties of a network with delayed reverberating projections. The macroscopic behavior is analyzed by means of a mean-field approximation. Numerical simulations, however, show that the microscopic dynamics has a surprisingly rich structure that does not show up in a mean-field description. We have thus performed extensive numerical experiments in order to quantify the ability of the network to serve as a dynamical working memory and its vulnerability by noise. In a second step, we develop a more realistic conductance-based network model of the inferior olive consisting of about 20 multicompartment neurons that are coupled by gap junctions and receive excitatory and inhibitory synaptic input via AMPA and GABAergic synapses. The simulations show that results for the time-discrete model hold true in a time-continuous description.
Selectively Grouping Neurons in Recurrent Networks of Lateral Inhibition
Authors: Xie Xiaohui , Hahnloser Richard H. R. , Seung H. Sebastian
Published: November 2002

Winner-take-all networks have been proposed to underlie many of the brain's fundamental computational abilities. However, notmuchisknown about how to extend the grouping of potential winners in these networks beyond single neuron or uniformly arranged groups of neurons. We show that competition between arbitrary groups of neurons can be realized by organizing lateral inhibition in linear threshold networks. Given a collection of potentially overlapping groups (with the exception of some degenerate cases), the lateral inhibition results in network dynamics such that any permitted set of neurons that can be coactivated by some input at a stable steady state is contained in one of the groups. The information about the input is preserved in this operation. The activity level of a neuron in a permitted set corresponds to its stimulus strength, amplified by some constant. Sets of neurons that are not part of a group cannot be coactivated by any input at a stable steady state. We analyze the storage capacity of such a network for random groups—the number of random groups the network can store as permitted sets without creating too many spurious ones. In this framework, we calculate the optimal sparsity of the groups (maximizing group entropy). We find that for dense inputs, the optimal sparsity is unphysiologically small. However, when the inputs and the groups are equally sparse, we derive a more plausible optimal sparsity. We believe our results are the first steps toward attractor theories in hybrid analog-digital networks.
An Unsupervised Ensemble Learning Method for Nonlinear Dynamic State-Space Models
Authors: Valpola Harri , Karhunen Juha
Published: November 2002

A Bayesian ensemble learning method is introduced for unsupervised extraction of dynamic processes from noisy data. The data are assumed to be generated by an unknown nonlinear mapping from unknown factors. The dynamics of the factors are modeled using a nonlinear state-space model. The nonlinear mappings in the model are represented using multilayer perceptron networks. The proposed method is computationally demanding, but it allows the use of higher-dimensional nonlinear latent variable models than other existing approaches. Experiments with chaotic data show that the new method is able to blindly estimate the factors and the dynamic process that generated the data. It clearly outperforms currently available nonlinear prediction techniques in this very difficult test problem.
Data-Reusing Recurrent Neural Adaptive Filters
Authors: Mandic Danilo P.
Published: November 2002

A class of data-reusing learning algorithms for real-time recurrent neural networks (RNNs) is analyzed. The analysis is undertaken for a general sigmoid nonlinear activation function of a neuron for the real time recurrent learning training algorithm. Error bounds and convergence conditions for such data-reusing algorithms are provided for both contractive and expansive activation functions. The analysis is undertaken for various configurations that are generalizations of a linear structure infinite impulse response adaptive filter.
Training a Single Sigmoidal Neuron Is Hard
Authors: Šíma Jiří
Published: November 2002

We first present a brief survey of hardness results for training feed forward neural networks. These results are then completed by the proof that the simplest architecture containing only a single neuron that applies a sigmoidal activation function σ:K→ [α, β], satisfying certain natural axioms (e.g., the standard (logistic) sigmoid or saturated-linear function), to the weighted sum of n inputs is hard to train. In particular, the problem of finding the weights of such a unit that minimize the quadratic training error within (β—α)2 or its average (over a training set) within—5(β—α)2 /(12n) of its infimum proves to be NP-hard. Hence, the well-known backpropagation learning algorithm appears not to be efficient even for one neuron, which has negative consequences in constructive learning.
A New Color 3D SFS Methodology Using Neural-Based Color Reflectance Models and Iterative Recursive Method
Authors: Cho Siu-Yeung , Chow Tommy W. S.
Published: November 2002

In this article, a new methodology for color shape from shading (SFS) problem is proposed. The problem of color SFS refers to the well-known fact that most real objects usually contain mixtures of diffuse and specular color reflections and are affected by the multicolored interreflection under unknown reflectivity. In this article, these limitations are addressed, and a new color SFS methodology is proposed. The proposed approach focuses on two main parts. First, a generalized neural-based color reflectance model is developed. Second, an iterative recursive method is developed to reconstruct a multicolor 3D surface. Experimental results on synthetic-colored objects and real-colored objects were performed to demonstrate the performance of the proposed methodology.
SHNEI KETUVIM AND RABBINIC INTERMEDIATION
Authors: Yadin Azzan
Published: November 2002

The present article argues that in the legal midrashim associated with the school of Rabbi Ishmael, the Mekhilta and the Sifre Numbers, "Two Verses Contradict and a Third Resolves" is not a general rule meant to resolve logical difficulties, as is generally assumed. The third verse resolution is employed in only two of the derashot that discuss biblical contradictions. A close reading of these derashot suggest that the issue at hand is not logical but theological and that in each case the third verse introduces a theological intermediary, denying the unmediated presence of God in the Tent of Meeting and at Sinai.
HIERONYMUS UND EPIPHANIUS VON SALAMIS ÜBER DAS JUDENTUM IHRER ZEIT
Authors: Lössl Josef
Published: November 2002

Compared to other Christian authors of the late 4th, early 5th century A.D. Jerome and Epiphanius of Salamis frequently write about Jews and Judaism. And they do so in a historical and biographical context which they largely share. Their frequent use of anti-Jewish polemics, however, has earned them a certain notoriety. But, as is argued in this paper, while their attitude in this respect is, of course, deplorable, it may be less a sign of their ignorance of, and distance from, than their proximity to, the Judaism of their time. Both, Jerome and Epiphanius, draw from very early Christian sources, sources still close to their Jewish roots. They define orthodoxy and heresy in terms of religious practices, very similar to Rabbinic Judaism, they are obsessed with scriptural detail, they reject the veneration of images, and they are interested in the languages and cultures of the Bible, far more than any other of their Christian contemporaries, or, indeed, Christians of any age. Considering their influential role in the history of Christian theology it may be worth looking at some of these aspects in detail, and see how they could have contributed not so much to the exclusion as to the preservation of the Jewish heritage in Christianity.
Apoyo social y ánimo depresivo en poblaciones de alto riesgo
Authors: Abril Vicente Javier
Published: November 2002

Este trabajo analiza la relación entre el apoyo social y la depresión en personas en alto riesgo psicosocial, teniendo en cuenta la mediación de determinadas variables psicológicas. Para comprobar estas relaciones, se ha analizado una muestra de 132 sujetos de ambos sexos, de edades comprendidas entre 18 y 80 años, que representan cuatro áreas de riesgo—personas de edad avanzada residentes y no residentes, enfermos crónicos del riñón y alcohólicos—obteniéndose una medición en las siguientes variables: participación e integración comunitaria, percepción de apoyo social en sistemas formales, autoestima social, emocionaly corporal, estrés percibido y depresión. Los resultados confirman tanto la hipótesis de los efectos principales como la de amortiguación según los planteamientos referidos desde nuestro enfoque teórico (Lin y Ensel. 1989), por cuanto aparecen tanto relaciones directas entre la percepción de apoyo social y la depresión, como relaciones indirectas entre ambas variables por la mediación de la autoestima y el estrés percibido en esa relación.
Jurados: de su composición y sus efectos en la toma de decisión grupal
Authors: Arce Ramón , Fariña Francisca , Real Santiago
Published: November 2002

A través de la LO 5/1995 se ha reinstaurado en España el Tribunal de Jurado. En el preámbulo de la Ley se deja abierta la puerta a las modificaciones que resulten necesario realizar para su eficaz funcionamiento para mejorar su calidad de ejecución. En cuanto a la decisión grupal, dos son las variables que tradicionalmente se han puesto en relación directa con la calidad de ejecución de losJurados: tamaño y regla resolutoria (p. ej., Zeisel, 1971; Hastie et al., 1983). Nuestros resultados, considerando las principales caracterizaciones delJurado, ponen de manifiesto que un Jurado de doce miembros regidos por una regla de unanimidad alcanza decisiones más consistentes y en los términos esperados.
Un estudio evaluativo sobre el ajuste y la ideoneidad de cursos de formación en organizaciones
Authors: Boada Joan , Tous Jordi , Pastor Estanislau
Published: November 2002

La formación en las organizaciones se entiende como no formal y se define como aquella actividad organizada y sistemática que se realiza fuera del marco del sistema oficial que facilita determinadas clases de aprendizaje a subgrupos particulares (Colom, Sarramona y Vázquez, 1994). Los cursos derivadospr etenden una formación «en» y «para» el trabajo. Así, los objetivos formativos explícitos de los cursos exponen los procesos esperables en función de las acciones que derivan directa o indirectamente de ésta. En un objetivo formativo debe considerarse la conducta final, el nivel de calidad de su ejecución y las condiciones bajo las cuales ocurre (Del Pozo, 1993). La evaluación de los objetivos es una técnica de obtención de información que posiblemente nos puede dar como resultado decisiones para categorizar los programas como «buenos» o «malos». La evaluación recoge la esencia dinámica del programa de formación (Goldstein, 1986). El objetivo de nuestro trabajo pretende efectuar un análisis comparativo de los objetivos formativos utilizados en cursos de formación. Respecto al método se han considerado los cursos formativos de 26 PYMES del ámbito de la provincia de Tarragona, se han analizado 126 objetivos aplicando la técnica del Análisis Dimensional (Secadas, 1988). Los resultados muestran una serie de dimensiones compuestas por conjuntos de objetivos, con una serie de limitaciones y aportaciones en la formulación de los mismos por parte de los formadores.
La imagen de las personas mayores mediante una tarea de asociación de atributos en familiares cuidadores
Authors: Colodrón María S. , Montorio Ignacio
Published: November 2002

El presente trabajo estudia la relación entre las imágenes que los cuidadores informales mantienen sobre el grupo de personas mayores en general y sobre el familiar mayor a quien cuidan en particular. Para ello se diseñó un instrumento basado en las técnicas de asociación. Una muestra de 95 sujetos agrupó 30 adjetivos según un criterio espontáneo de similaridad. Estos adjetivos habían sido obtenidos a partir de los utilizados por otra muestra de 100 sujetos para describir a personas con distintas características. Mediante el escalamiento multidimensional de la matriz de proximidades, se obtuvo una solución tridimensional que diferenció los adjetivos en cuatro agrupamientos: bienestar funcional, bienestar afectivo, afecto negativo aceptable y afecto negativo rechazable. Posteriormente, una muestra de 62 cuidadores seleccionaron, de entre los 30 adjetivos, aquellos que eran “aplicables” a una persona mayor en general y aquellos que eran “aplicables” a su familiar mayor. Los resultados muestran que mientras los cuidadores utilizan un mismo número de características “positivas” para describir a las personas mayores y a su familiar, eligen un mayor número de características “negativas” para describir al grupo de personas mayores. Finalmente, los análisis de regresión muestran que la imagen que los cuidadores mantienen de su familiar en relación a características de dependencia-independencia, salud-enfermedad, actividad-pasividad, etc. son explicadas parcialmentepor la imagen que mantienen de las personas mayores respecto a esas mismas características.
Diseño implementado para evaluar un Plan Institucional de Acción Positiva para las Mujeres
Authors: Erro Maite , Pizarro Maribel
Published: November 2002

El II Plan de Acción Positiva para las Mujeres, impulsado por el Instituto Vasco de la Mujer (Emakunde), propone 400 acciones estructuradas en 9 áreas de actuación diferentes. En su ejecución están implicados 23 Organismos Públicos (País Vasco, España). Este trabajo ha sido realizado entre Emakunde y la Universidad del País Vasco. Sus principales objetivos han sido: aumentar la evaluabilidad del Plan; establecer indicadores para evaluar su nivel de cumplimiento; y diseñar instrumentos de recogida de información. Además se consideró relevante incrementar la motivación y participación de los Organismos Públicos en el proceso de evaluación, y con tal fin se realizaron reuniones de trabajo con ellos para informarles sobre el diseño de evaluación. Los resultados obtenidos hasta el momento indican que la evaluabilidad del Plan ha aumentado de forma notable; los instrumentos de evaluación han posibilitado una recogida de datos más precisa y extensa; y se ha constatado una mayor implicación de los Organismos Públicos en el proceso de evaluación.
Factores asociados a la expresión del prejuicio como determinantes de la reducción de la discriminación
Authors: Falomir Juan Manuel , Sánchez-Mazas Margarita
Published: November 2002

El presente artículo analiza los procesos de reducción de la discriminación que acontecen como consecuencia del conflicto asociado a la expresión de un prejuicio. Dos factores asociados a la expresión del prejuicio son analizados como determinantes de este proceso. Por un lado se considera que determinadas relaciones entre grupos permiten la actual discriminación, y que su reducción acontecerá cuando una actitud desfavorable se exprese en el marco de una relación interpersonal que responsabilice al individuo de la expresión de tal prejuicio. En segundo lugar se considera que la reducción de la discriminación acontecerá cuando la expresión de una actitud desfavorable hacia un grupo vaya en contra de una norma antidiscriminatoria. Un estudio experimental sobre la discriminación que sufren los fumadores aporta resultados que confirman las predicciones establecidas por este modelo.
Incidencia del entorno residencial en los itinerarios socioeducativos y laborales de los adolescentes
Authors: García J. Miguel Ángel , Monteoliva Adelaida
Published: November 2002

Con el objetivo de analizar la incidencia del entorno de residencia sobre los itinerarios que van a seguir los jóvenes desde que acaban la escuela hasta su inserción laboral, se está llevando a cabo un estudio de carácter longitudinal de diez años de duración, sobre una muestra de 187 jóvenes que residen en contextos diferentes. Concretamente, 33 de los sujetos de la muestra viven internados en Residencias Escolares y 154 en el domicilio familiar. Los resultados que se presentan en este trabajo, corresponden a los datos obtenidos un año después de que los sujetos finalizaran la enseñanza general obligatoria.

Al comparar las opciones seguidas al terminar la E.G.B. por ambos grupos, se han podido constatar diferencias altamente significativas entre ellos. Los resultados obtenidos en esta primera transición indican que, una de las variables que mejor predice la opción en la que se van a situar los sujetos al acabar la E.G.B., es el tipo de residencia (vivir con la familia o en Residencia Escolar) de los jóvenes.
La preocupación ambiental como función de valores y creencias
Authors: González Antonio , Amérigo María
Published: November 2002

Los valores personales se están convirtiendo en una variable fundamental para explicar y entender la preocupación por la protección del medio ambiente.

Utilizando una muestra de 408 estudiantes de la Universidad de Castilla-La Mancha se estudia la preocupación ambiental a través de las relaciones entre los valores personales, las creencias sobre las condiciones ambientales y las intenciones de conducta proambiental. Los resultados obtenidos muestran que los valores biosféricos, altruistas y de apertura al cambio y también las creencias biosféricas y socioaltruistas están significativamente relacionados con las intenciones de conducta proambiental. Con respecto al género, las mujeres manifiestan mayores intenciones de realizar comportamientos proambientales. Finalmente, se encontró una estrecha correspondencia entre los sentimientos de obligación moral y la preocupación ambiental.
El estudio del estigma desde la atribucion causal
Authors: Marichal Fátima , Quiles María Nieves
Published: November 2002

El estigma, como marca diferenciadora, elicita una reacción afectiva y emocional, así como una respuesta conductual hacia los portadores de dicha marca. Desde un enfoque atribucionalse asume que lo que origina esas respuestas conductualesy afectivas hacia los estigmatizados, no sólo está determinado por la propia naturaleza del estigma sino, también, por las explicaciones que se atribuyen a la causa del estigma. El objetivo de esta investigación es, por tanto, estudiar el efecto de la información causal sobre el estigma en las respuestas afectivas y en la intención de conductas de los no estigmatizados hacia los estigmatizados. Con este fin se diseña un estudio experimental en el que se analiza las diferencias en las respuestas afectivas y las intenciones de conducta hacia distintos tipos de estigmas. Los resultados muestran que las diferencias en cuanto a respuestas afectivas y conductuales que reciben los grupos estigmatizados, se diluyen ante la presencia de información causal sobre el stigma.
De la confianza a la productividad: indicadores de salud mental positive infantile
Authors: Miguel María Dolores , Vives María José
Published: November 2002

Siguiendo las recomendaciones propuestas por la OMS respecto a la importancia de la prevención y evaluación de la salud mental infantil así como la conveniencia de disponer de indicadores que permitan su valoración y fomento, aportamos en este trabajo la construcción del Test de Salud Mental Positiva Infantil (TSMPI), en cuya estructura se incorporan cuatro Criterios de Salud Mental Positiva definidos por Marie Jahoda en su Modelo Conceptual Current Concepts of Positive Mental Health (1958) y las cuatro primeras etapas de la Teoría del Desarrollo Psicosocial (Etapas de la Epigénesis del Ego) de Erik H. Erikson (1963) La interrrelación de estos dos marcos teóricos ha permitido la elaboración de cinco indicadores de salud mental positiva secuenciales, que corresponden a las edades de 8 a 12 años: Confianza, Autoconcepto, Autonomía, Iniciativa e Industria.
Apoyo social, integración social y salud mental
Authors: Sánchez Esteban
Published: November 2002

El apoyo social se ha convertido en un concepto cada vez más popular y en una herramienta de trabajo muy útil para el estudio de los factores psicosociales relacionados con la salud mental. A pesar de la existencia de una amplia bibliografía demostrando la relación positiva entre apoyo social y bienestar psicológico, existen importantes problemas en torno al concepto de apoyo social. En primer lugar, un desacuerdo definicional. En segundo lugar, una polémica en torno a los mecanismos a través de los cuales se da la asociación entre apoyo social y salud mental. Estos debates pueden resumirse en dos hipótesis rivales: el modelo de efectos directos y el modelo de efectos protectors.

El presente artículo intenta clarificar este debate introduciendo el concepto de integración social. Para ello, se elabora dicho concepto a partir de la obra de Emile Durkheim, enfatizando el posible papel de la anomia en el deterioro psicológico. Finalmente, se discuten las implicaciones de este análisis para las teorías sobre apoyo social y la relación entre el apoyo social y la salud mental.
Presentación del proyecto de investigación “ICYLCABE-1996”: identidades culturales y lingüísticas en las Comunidades Autónomas Bilingües (CAB) de España
Authors: Azurmendi María-José , Bourhis Richard Y.
Published: November 2002

El proyecto de investigación ICYLCABE-1996 estudia las Identidades culturales y lingüísiticas en las comunidades autónomas bilingües (CAB) de España, desarrolladas durante la nueva etapa autonómica, en relación con otros procesos psicosociales: 1) las creencias sobre la vitalidad etnolingüística de las lenguas y de los grupos lingüísticos en contacto; 2) la red individual de contactos lingüísticos y culturales; 3) el nivel de competencia en ambas lenguas en contacto; 4) el uso de ambas lenguas en contacto; 5) las relaciones intergrupales: actitudes, distancia social, discriminación, cooperación y tensión intergrupales; 6) las concepciones de ciudadanía. De este modo se quiere contribuir al proceso de normalización lingüística y cultural abierto tras la Constitución Española de 1978, hace ahora 20 años, que está desarrollándose en las distintas CAB.
DOCK2 associates with CrkL and regulates Rac1 in human leukemia cell lines
Authors: Nishihara Hiroshi , Maeda Masae , Oda Atsushi , Tsuda Masumi , Sawa Hirofumi , Nagashima Kazuo , Tanaka Shinya
Published: November 2002

The CDM (ced-5 of Caenorhabditis elegans,DOCK180 [downstream of Crkwith molecular weight of 180 kDa] of humans, andmyoblast city of Drosophila melanogaster) family of proteins has been shown to play a pivotal role in the integrin-mediated signaling pathway under the regulation of an adaptor moleculec-CT10–related kinase II (c–Crk-II) in adherent cells. Recently, hematopoietic cell–specific CDM protein DOCK2 has been shown to be indispensable for lymphocyte migration. However, the regulatory mechanism for DOCK2 is still unknown because DOCK2 lacks a c–Crk-II binding consensus motif. In this study, we demonstrated that DOCK2 bound to CrkL, which is present exclusively in hematopoietic cells both in vivo and in vitro, and we also found that 2 separate regions of DOCK2 contributed to its binding to Src homology 3 (SH3) domain of CrkL. Colocalization of DOCK2 with Crk-like (CrkL) and F-actin was shown by immunocytochemical analysis with the use of Jurkat cells. We also found that CrkL-induced activation of small guanine triphosphatase (GTPase) Rac1 was significantly inhibited by the DOCK2-dCS mutant in 293T cells. Furthermore, the association of DOCK2 and Vav, the guanine-nucleotide exchanging factor (GEF) for Rac1, was demonstrated in Jurkat cells. Finally, the stable expression of DOCK2-dCS mutant in Jurkat cells was shown to reduce cell attachment. These data suggest the presence of a novel protein complex of CrkL, DOCK2, and Vav to regulate Rac1 in leukemia cell lines.
Antagonistic effect of NK cells on alternatively activated monocytes: a contribution of NK cells to CTL generation
Authors: Geldhof Anja B. , Van Ginderachter Jo A. , Liu YuanQing , Noël Wim , Raes Geert , De Baetselier Patrick
Published: November 2002

Natural killer (NK) cells fulfill essential accessory functions for the priming of antigen-specific cytotoxic T lymphocytes (CTLs). On the basis of a NKG2D-ligand–positive tumor model, we obtained results implicating NK-mediated regulatory as well as NK-mediated cytolytic activities in the initiation and persistence of CTL activity. Indeed, CD8+ T-cell–dependent tumor rejection requires NK cell function in vivo, because tumors will progress both on depletion of NK cells or in the absence of optimal NK activity. Here we provide evidence that the absence of NK cells during subcutaneous tumor growth will abrogate generation of antitumor CTL responses and that this process can be linked to the expansion of alternatively activated monocytes. Indeed, our in vitro studies demonstrate that in splenic cultures from NK-deficient tumor-bearing mice, lack of type 1–associated cytokines correlates with the presence of type 2 (alternatively activated) monocytes and the production of type 2 cytokines. Furthermore, these type 2 monocyte-containing splenic adherent populations potently suppress subsequent memory CTL restimulation. We evaluated the role of NK lytic effector functions in the efficient switch of the immune system toward classical (type 1) activation by including differentially activated monocytic populations as targets in cytotoxicity assays. The results indicate that the accessory function of NK cells depends partially on the ability of activated NK cells to preferentially engage type 2 antigen-presenting cells. Thus, when the immune system tends to be type 2 oriented, NK cells can drive an efficient type 2 → type 1 switch in the population of antigen-presenting cells to provide signaling for the generation of CTLs.
Prevention of leptin binding to its receptor suppresses rat leukemic cell growth by inhibiting angiogenesis
Authors: Iversen Per Ole , Drevon Christian Andre , Reseland Janne Elin
Published: November 2002

Leptin promotes the growth and viability of hematopoietic cells, and it also stimulates microvessel formation, indicating a role for leptin in angiogenesis. Acute myelocytic leukemia (AML) remains a disease with poor prognosis. Similar to solid tumors, it probably requires angiogenesis to ensure adequate supplies of nutrients. We studied rats with transplanted AML to test if a neutralizing anti–leptin receptor monoclonal antibody (mAb) (anti–OB-R) could inhibit leukemogenesis. At 4 weeks after transplantation, the bone marrow contained about 80% leukemic cells as assayed with a specific mAb and flow cytometry. Microscopic examination of bone marrow sections stained with an anti–von Willebrand mAb revealed a marked increase in microvessel density in the leukemic rats compared with controls. Treatment with anti–OB-R for 3 weeks more than halved the content of bone marrow leukemic cells with a concomitant, substantial decrease in angiogenesis. A parallel experiment using an irrelevant anticasein mAb showed no effect on either leukemic cell growth or angiogenesis. We could not detect surface expression of the leptin receptor on the leukemic cells, but on mononuclear cells from healthy rats. The anti–OB-R did not affect in vitro proliferation of leukemic cells whereas proliferation of the mononuclear cells was markedly impaired. The anti–OB-R had no effect on either leukemic cell growth or angiogenesis in leukemic fa/fa rats with a mutated leptin receptor. We conclude that leptin stimulates leukemic cell growth in vivo by promoting angiogenesis. Inhibition of binding of leptin to its receptor might be a new adjunct therapy in AML.
Outcome after induction chemotherapy for older patients with acute myeloid leukemia is not improved with mitoxantrone and etoposide compared to cytarabine and daunorubicin: a Southwest Oncology Group study
Authors: Anderson Jeanne E. , Kopecky Kenneth J. , Willman Cheryl L. , Head David , O'Donnell Margaret R. , Luthardt Frederick W. , Norwood Thomas H. , Chen I-Ming , Balcerzak Stanley P. , Johnson David B. , Appelbaum Frederick R.
Published: November 2002

Complete remission and long-term survival rates are low for older adults treated for acute myeloid leukemia (AML). Because of favorable phase 2 data using mitoxantrone and etoposide, we conducted a phase 3 study (SWOG-9333) in which patients over 55 years of age with previously untreated AML were randomized to receive mitoxantrone (10 mg/m2 per day × 5) and etoposide (100 mg/m2per day × 5) [ME], or cytarabine (200 mg/m2 per day × 7) and daunorubicin (45 mg/m2 per day × 3) [AD] as induction therapy. The randomization was stratified by age, onset of leukemia, and multidrug resistance phenotype. Over a 4-year period, 328 eligible patients from 66 institutions were enrolled. The complete remission rate was 34% (95% confidence interval [CI] 26%-41%) for patients in the ME and 43% (CI 35%-51%) for patients in the AD treatment arm (one-tailedP value .96). The rates of resistant disease were 43% (CI 35%-51%) and 34% (CI 27%-42%), respectively, for the 2 treatment arms (one-tailed P value .95). The estimated overall survival at 2 years was 11% (CI 6%-15%) and 19% (CI 12%-25%) for patients randomized to ME and to AD induction therapy, respectively (one-tailed P value .99). After accounting for the independent prognostic factors associated with survival (karyotype, performance status, age, white blood cell count), exploratory analysis suggested there was a worse survival for patients who received ME compared with AD induction therapy (2-tailed P value .0066). We conclude that the results of our study do not demonstrate any benefit to the use of ME induction chemotherapy instead of AD in older patients with AML.
Development of sensitive fluorescent assays for embryonic and fetal hemoglobin inducers using the human β-globin locus in erythropoietic cells
Authors: Vadolas Jim , Wardan Hady , Orford Michael , Voullaire Lucille , Zaibak Faten , Williamson Robert , Ioannou Panayiotis A.
Published: November 2002

Reactivation of fetal hemoglobin genes has been proposed as a potential therapeutic procedure in patients with β-thalassemia, sickle cell disease, or other β-hemoglobinopathies. In vitro model systems based on small plasmid globin gene constructs have previously been used in human and mouse erythroleukemic cell lines to study the molecular mechanisms regulating the expression of the fetal human globin genes and their reactivation by a variety of pharmacologic agents. These studies have led to great insights in globin gene regulation and the identification of a number of potential inducers of fetal hemoglobin. In this study we describe the development of enhanced green fluorescence protein (EGFP) reporter systems based on bacterial artificial chromosomes (EBACs) to monitor the activity of the ε-, Gγ-, Aγ-, δ-, and β-globin genes in the β-globin locus. Additionally, we demonstrate that transfection of erythroleukemia cells with our EBACs is greatly enhanced by expression of EBNA1, which also facilitates episomal maintenance of our constructs in human cells. Our studies in human cells have shown physiologically relevant differences in the expression of each of the globin genes and also demonstrate that hemin is a potent inducer of EGFP expression from EGFP-modified ε-, Gγ-, andAγ-globin constructs. In contrast, the EGFP-modified δ- and β-globin constructs consistently produced much lower levels of EGFP expression on hemin induction, mirroring the in vivo ontogeny. The EGFP-modified β-globin eukaryotic BAC (EBAC) vector system can thus be used in erythroleukemia cells to evaluate induction of the ε- and γ-globin genes from the intact human β-globin locus.
Human T-cell lymphotropic virus oncoprotein Tax represses TGF-β1 signaling in human T cells via c-Jun activation: a potential mechanism of HTLV-I leukemogenesis
Authors: Arnulf Bertrand , Villemain Aude , Nicot Christophe , Mordelet Elodie , Charneau Pierre , Kersual Joëlle , Zermati Yaël , Mauviel Alain , Bazarbachi Ali , Hermine Olivier
Published: November 2002

Human T-cell leukemia virus I is the etiologic agent of adult T-cell leukemia (ATL), an aggressive T-cell malignancy. The viral oncoprotein Tax, through the activation of nuclear factorκB (NF-κB), CCAAT-enhancer binding protein (CREB), and activated protein-1 (AP-1) pathways, is a transcriptional regulator of critical genes for T-cell homeostasis. In ATL cells, activated AP-1 complexes induce the production of transforming growth factor β1 (TGF-β1). TGF-β1 is an inhibitor of T-cell proliferation and cytotoxicity. Here we show that, in contrast to normal peripheral T cells, ATL cells are resistant to TGF-β1–induced growth inhibition. The retroviral transduction of the Tax protein in peripheral T cells resulted in the loss of TGF-β1 sensitivity. Transient transfection of Tax in HepG2 cells specifically inhibited Smad/TGF-β1 signaling in a dose-dependent manner. In the presence of Tax transfection, increasing amounts of Smad3 restored TGF-β1 signaling. Tax mutants unable to activate NF-κB or CREB pathways were also able to repress Smad3 transcriptional activity. Next we have demonstrated that Tax inhibits TGF-β1 signaling by reducing the Smad3 DNA binding activity. However, Tax did not decrease the expression and the nuclear translocation of Smad3 nor did it interact physically with Smad3. Rather, Tax induced c-Jun N-terminal kinase (JNK) activity and c-Jun phosphorylation, leading to the formation of Smad3/c-Jun complexes. Whereas c-Jun alone abrogates Smad3 DNA binding, cotransfection of Tax and of a dominant-negative form of JNK or a c-Jun antisense-restored Smad3 DNA binding activity and TGF-β1 responsiveness. In ATL and in normal T cells transduced by Tax, c-Jun was constitutively phosphorylated. Thus, we describe a new function of Tax, as a repressor of TGF-β1 signaling through JNK/c-Jun constitutive activation, which may play a critical role in ATL leukemogenesis.