Characterization of three human sec14p-like proteins: a-Tocopherol

Three closely related human sec14p-like proteins (hTAP1, 2, and 3, or SEC14L2, 3, and 4, respectively) have been described. These proteins may participate in intracellular lipid transport (phospholipids, squalene, tocopherol analogues and derivatives) or influence regulatory lipid-dependent events. Here, we show that the three recombinant hTAP proteins associate with the Golgi apparatus and mitochondria, and enhance the in vitro transport of radioactively labeled α-tocopherol to mitochondria in the same order of magnitude as the human α-tocopherol transfer protein (α-TTP). hTAP1 and hTAP2 are expressed in several cell lines, whereas the expression level of hTAP3 is low. Expression of hTAP1 is induced in human umbilical cord blood-derived mast cells upon differentiation by interleukin 4. In tissues, the three hTAPs are detectable ubiquitously at low level; pronounced and localized expression is found for hTAP2 and hTAP3 in the perinuclear region in cerebellum, lung, liver and adrenal gland. hTAP3 is well expressed in the epithelial duct cells of several glands, in ovary in endothelial cells of small arteries as well as in granulosa and thecal cells, and in testis in Leydig cells. Thus, the three hTAPs may mediate lipid uptake, secretion, presentation, and sub-cellular localization in a tissue-specific manner, possibly using organelle- and enzyme-specific docking sites.

La situación de los museos españoles ante la crisis. El patrimonio implicado

La crisis como coyuntura y tránsito a una nueva situación, y el cambio social que parece conllevar, lejos de ser un fenómeno exclusivamente actual, viene acompañando a los museos españoles desde décadas atrás, debido a indecisiones, faltas de planificación, cambios políticos y de estrategias de funcionamiento. Pero será a partir de la Transición democrática, y la década de 1980, en que comenzará a fraguarse la llamada “burbuja” de los museos, que estalla bajo el “efecto Guggenheim” a finales del siglo XX, seguida de la merma de presupuestos oficiales para el sostenimiento del sistema museístico que trae como consecuencia la tan mencionada “crisis” económica desde aproximadamente 2008. El artículo examina esta situación y advierte de que el momento delicado que viven los museos en la actualidad es ocasión para replantearse su futuro y adaptarse a una nueva realidad cambiante. El Museo Etnológico de Navarra “Julio Caro Baroja” constituye un caso de adaptación a tales circunstancias.

La exploración del litoral atlántico norteafricano según el periplo de Hannón de Cartago

El periplo de Hannón, frente a las propuestas que lo interpretan como una obra literaria, creemos que recoge un periplo auténtico, que sólo alcanzó cabo Juby y algunas de las Islas Canarias. Las refundaciones cartaginesas fueron todas en la Mauretania fértil, en los 7 primeros días de la expedición. Desde el islote de Kérne, en la expedición primó una primera exploración de evaluación, indicativo de que se trataba de apenas 2 o 3 barcos, con una tripulación limitada, que evitaban enfrentamientos con la población local. Los intérpretes Lixítai parecen conocer todos los puntos explorados, el río Chrétes, los etíopes del Alto Atlas costero, el gran golfo caluroso que finalizaba en el Hespérou Kéras, el volcán Theôn Óchema, o las gentes salvajes que denominaban Goríllai. Probablemente la mayor sorpresa fuese encontrar un volcán activo, emitiendo lava, que pudo ser la razón última para redactar este periplo. La falta de agua, alimentos y caza como razón para finalizar la expedición exploratoria sólo es comprensible en un trayecto corto que alcanzó hasta el inicio del desierto del Sahara. Otro tanto sucede con la ausencia de ríos importantes al Sur del río Chrétes, una clara prueba de que no se alcanzaron latitudes ecuatoriales y que los barcos se fueron alejando de la costa norteafricana.

Étude de la reconstitution de l’immunité spécifique au cytomégalovirus et au virus de la varicelle suite à la transplantation de sang de cordon ombilical

La transplantation de sang de cordon ombilical (TSCO) constitue un traitement de choix pour une multitude de pathologies hématologiques malignes et non malignes chez l’enfant et dans certains cas l’adulte. La TSCO est associée à certaines complications, dont une reconstitution immunitaire plus lente et une incidence élevée d’infections opportunistes, notamment celles reliées au cytomégalovirus (CMV) et au virus varicella-zoster (VZV). Dans le cadre de ce travail, nous nous sommes intéressés dans un premier temps à la caractérisation de la reconstitution immunitaire spécifique au CMV et au VZV. Nos résultats ont démontré que la reconstitution de l’immunité cellulaire ne requiert ni un statut séropositif pré-transplantation ni le développement de la maladie. De plus, des reconstitutions spontanées ont été détectées chez certains patients séronégatifs vis-à-vis du CMV ou du VZV. Outre le fait qu’elle se manifeste surtout à partir de 6 mois post-transplantation, ladite reconstitution mérite le qualificatif de « protectrice » en termes de réactivations virales et du développement de signes cliniques lorsqu’une fréquence de 150 cellules produisant l’IFN-γ/million est dépassée. Toutefois, moins de 5% des patients développent une réponse T anti-VZV et anti-CMV au cours 100 premiers jours suivant la TSCO. Il est donc possible que les lymphocytes CD8+ T provenant du SCO, comparativement à leurs homologues provenant de la moelle osseuse (MO), présentent un défaut de fonctionnalité, communément appelé « épuisement clonal ». La caractérisation du répertoire de récepteurs inhibiteurs exprimés par les cellules T CD8+ suivant la TSCO ou la transplantation de moelle osseuse (TMO) a révélé une augmentation significative de la fréquence des cellules exprimant PD-1 tôt suivant la transplantation. Cette population, caractérisée majoritairement par un phénotype effecteur-mémoire (EM), démontre une perte significative de la capacité proliférative et exprime moins d'IFN-γ, d'IL-2, de TNF-α et de CD107a. Une meilleure caractérisation de la reconstitution immunitaire après TSCO permettrait, d'une part de sélectionner des biomarqueurs en vue d’une meilleure gestion des patients à risques de développer des infections virales et/ou de rechuter, et d'autre part d'améliorer leur pronostic.

Bacterial translocation in rats nonfunctioning diverted distal colon

To investigate whether the alterations of the diverted colon segment mucosa, evidenced in fecal colitis, would be able to alter Bacterial Translocation (BT). Methods: Sixty-two Wistar male rats ranging from 220 to 320 grams of weight, were divided in two groups: A (Colostomy) and B (Control), with 31 animals each one. In group A, all animals underwent end colostomy, one stoma, in ascending colon; and in the 70th POD was injected in five rats, by rectal route – diverted segment - 2ml of a 0.9% saline solution in animals (A1 subgroup); in eight it was inoculated, by rectal route, 2ml of a solution containing Escherichia coli ATCC 25922 (American Type Culture Collection), in a concentration of 108 Colony Forming Unit for milliliters (CFU/ml) - A2 Subgroup; in ten animals the same solution of E. coli was inoculated, in a concentration of 1011 CFU/ml (A3 Subgroup); and in eight it was collected part of the mucus found in the diverted distal colonic segment for neutral sugars and total proteins dosage (A4 subgroup). The animals from the group B underwent the same procedures of group A, but with differences in the colostomy confection. In rats from subgroups A1, A2, A3, B1, B2, and B3 2ml of blood were aspirated from the heart, and fragments from mesenteric lymphatic nodule, liver, spleen, lung and kidney taken for microbiological analysis, after their death. This analysis consisted of evidencing the presence of E. coli ATCC 25922 CFU. Mann-Whitney and ANOVA Tests were applied as analytic techniques for association of variables. Results: The occurrence of BT was evidenced only in those animals in which inoculated concentration of E. coli ATCC 25922, reached levels of 1011CFU/ml, i.e. in Subgroups A3 and B3, although, being significantly greater (80%) in those animals without colostomy (subgroup B3) when compared to the ones with colostomy (20%) from the subgroup A3 (P <0.05). Lung, liver and mesenteric lymphatic nodules were the tissues with larger percentile of bacterial recovery, so much in subgroup A3, as in B3. Blood culture was considered positive in 60% of the animals from subgroup B3 and in 10% of those from subgroup A3 (p <0.05). There was greater concentration of neutral sugars, in subgroup A4 - mean 27.3mg/ml -, than in subgroup B4 - mean 8.4mg/ml - (P <0.05). Conclusion: The modifications in the architecture of intestinal mucosa in colitis following fecal diversion can cause alterations in the intestinal barrier, but it does not necessarily lead to an increased frequency of BT

Bisphenol A alters transcript levels of biomarker genes for major depressive disorder in vascular endothelial cells and colon cancer cells

Bisphenol A (BPA) is capable of mimicking endogenous hormones with potential consequences for human health and BPA exposure has been associated with several human diseases including neuropsychiatric disorders. Here, quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) results show that BPA at low concentrations (10 ng/mL and 1 μg/mL) induces differential transcript levels of four biomarker genes for Major Depressive Disorder (MDD) in HT29 human colon adenocarcinona cell line and Human Umbilical Vein Endothelial Cells (HUVEC). These results substantiate increasing concerns of BPA exposure in levels currently detected in humans.

Le cordon ombilical humain, source de cellules pour le génie tissulaire : Isolement, caractérisation et production de substituts humains

Le cordon ombilical humain suscite beaucoup d’intérêt comme source de cellules à des fins de recherche et de thérapie. Quatre types cellulaires majeurs - les cellules épithéliales, stromales, musculaires lisses et endothéliales - composent les tissus solides du cordon ombilical. Quelques-uns de ces types cellulaires ont été utilisés en recherche scientifique depuis longtemps, alors que d’autres commencent à peine à dévoiler leur potentiel. Nous avons développé un protocole unique pour l’extraction séquentielle de tous ces types cellulaires d’un seul cordon ombilical, permettant ainsi la reconstruction à partir d’une même source. La combinaison des techniques de perfusion, immersion et explants a mené à la mise en culture et à l’expansion de ces cellules, dont les cellules épithéliales et les cellules stromales de la gelée de Wharton qui ont été caractérisées plus en détail par l’immunomarquage de protéines spécifiques. Leur potentiel pour la médecine régénératrice a été démontré par la production de tissus par génie tissulaire. Un vaisseau sanguin composé de cellules stromales et de cellules musculaires lisses du cordon ombilical démontra une résistance substantielle à l’éclatement. Les capacités de différenciation des cellules épithéliales ont été étudiées dans le contexte d’une peau bilamellaire reconstruite en combinaison avec des kératinocytes, des fibroblastes dermiques, et des cellules stromales de la gelée de Wharton. Les cellules épithéliales ont montré une différenciation similaire à celle des kératinocytes lorsque cultivées sur des fibroblastes dermiques et exposées à l’air, tandis que sur des cellules stromales du cordon, elles ont subi une désorganisation. Finalement, la différenciation des cellules stromales a été induite en culture vers plusieurs types cellulaires afin de compléter cette étude. L’ensemble des résultats fait ressortir l’importance non seulement de l’influence du milieu physique sur la croissance et la différenciation des cellules, mais également de l’impact de la provenance des cellules sur la qualité des tissus reconstruits.

Presentación

En el mes de octubre del 2005 se celebró la I Semana de Ciencias Sociales de la Facultad de Ciencias Sociales de la Universidad Nacional. Esta feliz e importante iniciativa, que tuvo como gestores al Decano de la Facultad de Ciencias Sociales de entonces, M.Sc. José Carlos Chinchilla Coto, a la Vicedecana M.Sc. Nelly López Alfaro y como responsable al Licenciado Roberto Pineda Ibarra,logró reunir un grupo significativo de académicos(as) e investigadores que durante varios días tuvieron la oportunidad de plantear temas y problemas relacionados con sus campos de interés o con intereses generales de las Ciencias Sociales académicas.

Calidad del agua de los ríos de la microcuenca IV del Río Virilla

En la evaluación de la calidad del agua de los cauces de los Ríos Tibás, Lajas, Tranqueras y Tures de la Microcuenca IV del Río Virilla se aplicaron dos índices basados en parámetros físicos, químicos y bacteriológicos con el fin de brindar recomendacionespara la gestión y el uso del recurso hídrico. Los índices aplicados fueron el Índice de Calidad de la Fundación Nacional de Sanidad de los Estados Unidos de América (ICAFNS) y el Índice del Sistema Holandés de Valoración de la Calidad del Agua.

Comunidades virtuales para promover la innovación académica universitaria: UNA realidad

Los nuevos avances en las tecnologías para la información y comunicación (TIC) y los enfoques pedagógicos modernos crean nuevas oportunidades para diseñar ambientes innovadores de aprendizaje. Sin embargo, a pesar de los esfuerzos significativos que se realizan en las universidades para cambiar la naturaleza del aprendizaje, el modelo tradicional de educación es todavía ampliamente utilizado, y constituye una de las principales razones la inadecuada preparación de los académicos para enfrentar estos nuevos retos. Este artículo muestra los resultados preliminares de una iniciativa que se desarrolló en la Universidad Nacional de Costa Rica (UNA) mediante el proyecto “Comunidad de Práctica Virtual para la Innovación Académica en las Sedes Regionales de la Universidad Nacional”, el cual pretende promover un cambio cualitativo en la práctica docente de los académicos de las sedes regionales con el desarrollo y la aplicación de estrategias pedagógicas innovadoras y las TIC, creando a la vez condiciones para lograr un mayor grado de comunicación y compañerismo entre los docentes de las sedes regionales. El proyecto buscaba explorar un cambio en el enfoque de desarrollo profesional, de una formación tradicional a un aprendizaje en la práctica, utilizando para esto las estructuras conceptuales de las comunidades de práctica.

Desechos líquidos: el caso de las salas de belleza

El objetivo principal de este estudio preliminar consistió en el análisis de las fortalezas y las debilidades en el manejo de desechos líquidos en cinco salas de belleza para apoyar estudios posteriores. Adicionalmente, se realizó un muestreo de aguas residuales en dos de los salones de belleza, S1 y S2, en los que se recolectaron muestras compuestas durante un día laboral. Los valores promedio de pH, amonio, DQO y grasas y aceites superaron los límites permitidos en la legislación costarricense, estos fueron respectivamente: 7,96 ± 0,01; 0,38 ± 0,01 mg N/L; 77 ± 13 mg O2/L y 1905,0 ± 0,1 mg/L, para S1 y 8,88 ± 0,01, 57,4 ±0,2 mg N/L; 240 ± 128 mg O2/L y 2775,0 ± 0,1 mg/L, para S2. Se evidenció que la calidad del agua y el cumplimiento de la normativa vigente son dependientes del tipo de productos utilizados (biodegradables o no, con o sin amoniaco). Aunque los volúmenes de vertido son intermitentes y pequeños, estos desechos pueden impactar negativamenteel ambiente.

Promotion and diffusion of tha career Bachelor and Licenciature of Mathematics Teaching in rural areas of Costa Rica project: effects and results

This article describes the purpose and activities of the project Promoting Mathematics Education in Rural Areas of Costa Rica. The activity has focused on two objectives. First, supporting and monitoring students who have expressed interest in studying a mathematics teacher. To achieve this, it has been working with students who have an ideal profile for the career, mainly from rural areas. The second objective is to conduct training workshops for high school in-service teachers, to strengthen and improve their knowledge in the area of mathematics. Among the results of the project, it can be highlighted a significant increase in the enrollment of students in the career of Mathematics Education in 2010 and 2011, and the training processes in the field of Real Functions of Real Variable and Geometry at different regional areas mostly rural as Aguirre, Sarapiquí, Coto, Buenos Aires, Limón, Cañas, Pérez Zeledón, Nicoya, Los Santos, Turrialba, Puriscal, Desamparados, San Carlos, Puntarenas, Limón, Liberia, Santa Cruz y Upala.

The virtual class as a knowledge democratization model

This paper presents the conceptualization and use of a virtual classroom in the course EIF-200 Fundamentos de Informática, first course in the Information Systems Engineering career of the Universidad Nacional of Costa Rica. The virtual classroom is seen as a complement to the class and is conceived as a space that allows to centralize teaching resources, thereby promoting the  democratization of knowledge among students and teachers. Furthermore, this concept of virtual classroom helps to reduce the culture of individualism, present many times in university teaching practices, and contributes to create new opportunities to learn from other colleagues within a culture of reflection, analysis and respectful dialogue aimed to improve the teaching practices.

The regulation of AMP-activated protein kinase by vascular endothelial growth factor

The function of the vascular endothelium is to maintain vascular homeostasis, by providing an anti-thrombotic, anti-inflammatory and vasodilatory interface between circulating blood and the vessel wall, meanwhile facilitating the selective passage of blood components such as signaling molecules and immune cells. Dysfunction of the vascular endothelium is implicated in a number of pathological states including atherosclerosis and hypertension, and is thought to precede atherogenesis by a number of years. Vascular endothelial growth factor A (VEGF) is a crucial mitogenic signaling molecule, not only essential for embryonic development, but also in the adult for regulating both physiological and pathological angiogenesis. Previous studies by our laboratory have demonstrated that VEGF-A activates AMP-activated protein kinase (AMPK), the downstream component of a signaling cascade important in the regulation of whole body and cellular energy status. Furthermore, studies in our laboratory have indicated that AMPK is essential for VEGF-A-stimulated vascular endothelial cell proliferation. AMPK activation typically stimulates anabolic processes and inhibits catabolic processes including cell proliferation, with the ultimate aim of redressing energy imbalance, and as such is an attractive therapeutic target for the treatment of obesity, metabolic syndromes, and type 2 diabetes. Metabolic diseases are associated with adverse cardiovascular outcomes and AMPK activation is reported to have beneficial effects on the vascular endothelium. The mechanism by which VEGF-A stimulates AMPK, and the functional consequences of VEGF-A-stimulated AMPK activation remain uncertain. The present study therefore aimed to identify the specific mechanism(s) by which VEGF-A regulates the activity of AMPK in endothelial cells, and how this might differ from the activation of AMPK by other agents. Furthermore, the role of AMPK in the pro-proliferative actions of VEGF-A was further examined. Human aortic and umbilical vein endothelial cells were therefore used as a model system to characterise the specific effect(s) of VEGF-A stimulation on AMPK activation. The present study reports that AMPK α1 containing AMPK complexes account for the vast majority of both basal and VEGF-A-stimulated AMPK activity. Furthermore, AMPK α1 is localized to the endoplasmic reticulum when sub-confluent, but translocated to the Golgi apparatus when cells are cultured to confluence. AMPK α2 appears to be associated with a structural cellular component, but neither α1 nor α2 complexes appear to translocate in response to VEGF-A stimulation. The present study confirms previous reports that when measured using the MTS cell proliferation assay, AMPK is required for VEGF-A-stimulated endothelial cell proliferation. However, parallel experiments measuring cell proliferation using the Real-Time Cell Analyzer xCELLigence system, do not agree with these previous reports, suggesting that AMPK may in fact be required for an aspect of mitochondrial metabolism which is enhanced by VEGF-A. Studies into the mitochondrial activity of endothelial cells have proved inconclusive at this time, but further studies into this are warranted. During previous studies in our laboratory, it was suggested that VEGF-A-stimulated AMPK activation may be mediated via the diacylglycerol (DAG)-sensitive transient receptor potential cation channel (TRPCs -3, -6 or -7) family of ion channels. The present study can neither confirm, nor exclude the expression of TRPCs in vascular endothelial cells, nor rule out their involvement in VEGF-A-stimulated AMPK activation; more specific investigative tools are required in order to characterise their involvement. Furthermore, nicotinic acid adenine dinucleotide phosphate (NAADP)-stimulated Ca2+ release from acidic intracellular organelles is not required for AMPK activation by VEGF-A. Despite what is known about the mechanisms by which AMPK is activated, far less is known concerning the downregulation of AMPK activity, as observed in human and animal models of metabolic disease. Phosphorylation of AMPK α1 Ser485 (α2 Ser491) has recently been characterised as a mechanism by which the activity of AMPK is negatively regulated. We report here for the first time that VEGF-A stimulates AMPK α1 Ser485 phosphorylation independently of the previously reported AMPK α1 Ser485 kinases Akt (protein kinase B) and ERK1/2 (extracellular signal-regulated kinase 1/2). Furthermore, inhibition of protein kinase C (PKC), the activity of which is reported to be elevated in metabolic disease, attenuates VEGF-A- and phorbol 12-myristate 13-acetate (PMA)-stimulated AMPK α1 Ser485 phosphorylation, and increases basal AMPK activity. In contrast to this, PKC activation reduces AMPK activity in human vascular endothelial cells. Attempts to identify the PKC isoform responsible for inhibiting AMPK activity suggest that it is one (or more) of the Ca2+-regulated DAG-sensitive isoforms of PKC, however cross regulation of PKC isoform expression has limited the present study. Furthermore, AMPK α1 Ser485 phosphorylation was inversely correlated with human muscle insulin sensitivity. As such, enhanced AMPK α1 Ser485 phosphorylation, potentially mediated by increased PKC activation may help explain some of the reduced AMPK activity observed in metabolic disease.