39Ar-40Ar geochronology of mono- and polymetamorphic basement rocks

The 39Ar-40Ar technique is often used to date the metamorphic evolution of basement rocks. The present review article examines systematic aspects of the K-Ar decay system in different mineral chronometers frequently found in mono- and polymetamorphic basements (amphibole, biotite, muscovite/phengite, K-feldspar). A key observation is that the measured dissolution rate of silicates in aqueous fluids is many orders of magnitude faster, and has a much lower activation energy, than the rate of Fickian diffusion of Ar. The effects of this inequality are patchy age zonations, very much like those observed in many U-Pb chronometers, unaccompanied by intra-crystalline bell¬shaped Ar loss profiles. Recognizing the importance of the respective rate constants in field situations leads to re-evaluating the ages and the interpretive paradigms in classic examples such as the Central Alpine "Lepontine" amphibolite event and the Western Alpine eclogitic event.

Synesthetic experiences enhance unconscious learning

Synesthesia is characterized by consistent extra perceptual experiences in response to normal sensory input. Recent studies provide evidence for a specific profile of enhanced memory performance in synesthesia, but focus exclusively on explicit memory paradigms for which the learned content is consciously accessible. In this study, for the first time, we demonstrate with an implicit memory paradigm that synesthetic experiences also enhance memory performance relating to unconscious knowledge.

An Exploration Based Cognitive Bias Test for Mice: Effects of Handling Method and Stereotypic Behaviour

Behavioural tests to assess affective states are widely used in human research and have recently been extended to animals. These tests assume that affective state influences cognitive processing, and that animals in a negative affective state interpret ambiguous information as expecting a negative outcome (displaying a negative cognitive bias). Most of these tests however, require long discrimination training. The aim of the study was to validate an exploration based cognitive bias test, using two different handling methods, as previous studies have shown that standard tail handling of mice increases physiological and behavioural measures of anxiety compared to cupped handling. Therefore, we hypothesised that tail handled mice would display a negative cognitive bias. We handled 28 female CD-1 mice for 16 weeks using either tail handling or cupped handling. The mice were then trained in an eight arm radial maze, where two adjacent arms predicted a positive outcome (darkness and food), while the two opposite arms predicted a negative outcome (no food, white noise and light). After six days of training, the mice were also given access to the four previously unavailable intermediate ambiguous arms of the radial maze and tested for cognitive bias. We were unable to validate this test, as mice from both handling groups displayed a similar pattern of exploration. Furthermore, we examined whether maze exploration is affected by the expression of stereotypic behaviour in the home cage. Mice with higher levels of stereotypic behaviour spent more time in positive arms and avoided ambiguous arms, displaying a negative cognitive bias. While this test needs further validation, our results indicate that it may allow the assessment of affective state in mice with minimal training— a major confound in current cognitive bias paradigms.

Genetic predictors of bladder cancer with an emphasis on methylation-related genes

Although tobacco exposure remains the prevailing risk factor for bladder cancer (BC), only a small percentage of exposed individuals develop cancer, suggesting that tobacco-related carcinogenesis is modulated by genetic susceptibility and possibly by DNA methylation-related events. Methylation patterns established by DNA methyltransferases (DNMTs) are influenced by dietary folate and genetic polymorphisms in the methylene-tetrahydrofolate reductase gene (MTHFR). Therefore, we hypothesized that DNA methylation-related genes, such as DNMT3B and MTHFR, might modulate BC risk. ^ In a study of 514 Caucasian BC cases and 498 healthy Caucasian controls examining the DNMT3B C46359T polymorphism, CC genotype was found to be a risk factor in women (Odds Ratio (OR) = 1.79), but not in men. This risk was further increased among women who were never smokers, consumed low dietary folate, and had adverse variants of MTHFR. In addition, higher DNMT3B expression among smokers was a risk factor (OR = 4.27) and correlated with genetic variants of the DNMT3B C46359T polymorphism, providing salient evidence for the risk associated with the CC variant. This suggests that the DNMT3B CC variant may confer a predisposition toward aberrant de novo methylation of CpG islands in critical tumor suppressor genes. ^ The convergence of alterations in DNMT3B, associated with promoter methylation, and reduced dietary folate consumption, accompanying global hypomethylation and genetic instability, may act synergistically to promote bladder carcinogenesis, especially in women. The results of this study unveiled new gender-specific paradigms of BC risk for women and demonstrated that this risk can be modified by folate consumption as well as polymorphisms in the folate pathway. ^

Behavioral Profile of the Novel Cannabinoid Agonist AM4054

Although cannabinoid drugs have been used for thousands of years both recreationally and therapeutically, little has been known about their mechanisms of action until recently. Since the discovery of the endogenous cannabinoid CB1 receptor in 1988, the behavioral profile of cannabinoid receptor ligands has been much more thoroughly defined. Cannabinoid CB1 agonists have been shown to produce a variety of behavioral effects including suppression of locomotion, catalepsy, hypothermia, and analgesia. Research has also demonstrated that these behavioral effects can be inhibited by CB1 receptor antagonists including SR 141716 and AM 251. Although behavioral indicators of anxiety including thigmotaxis have been observed in several different paradigms, there is inconclusive and often times contradictory evidence to define the role of anxiety in CB1 receptor activation. The present study addressed the behavioral profile of AM 4054, a novel full agonist at the CB1 receptor, as well as the ability of the CB1 antagonist AM 251 to reverse these effects. To further identify and expand research on the suppression of locomotion and induction of thigmotaxis with the administration of a CB1 agonist, experiment 1 was conducted in the open field. In this experiment, each rat (n=40) was randomly assigned one of the five treatments: vehicle, 0.16, 0.32, 0.64, or 1.25 mg/kg AM 4054. After a 30 minute pre-treatment, each subject was tested in the open field for 18 minutes. Results indicated that AM 4054 produced a dose-related suppression of locomotion as well as the subtle presence of thigmotaxis in two out of four doses. In experiment 2, subjects (n=40) received either vehicle or 2.0 or 4.0 mg/kg AM 251 60 minutes prior to testing. After 30 minutes, the subjects were given either a 0.3 mg/kg dose of AM 4054 or vehicle. After a total pretreatment duration of 60 minutes, the animals were tested on a battery of tasks including an 18 minute session in locomotor boxes. Experiment 2 was a continuation of a previous study conducted in the same lab, which confirmed the effects of AM 4054 on this tetrad of tasks as being consistent with other cannabinoid agonists. In this experiment the effects of AM 4054 were reversed by the administration of the CB1 antagonist AM 251. Past studies have shown that AM 4054 is a highly potent drug with behavioral actions similar to other cannabinoid CB1 agonists. Furthermore, AM 4054 can be a useful drug in future studies, and has potential therapeutic value for the treatment of various conditions.

Studies on behavioral regulations of morphine tolerance in rats

Opioids remain the drugs of choice in chronic pain treatment, but opioid tolerance, defined as a decrease in analgesic effect after prolonged or repeated use, dramatically limits their clinical utility. Opioid tolerance has classically been studied by implanting spinal catheters in animals for drug administration. This procedure has significant morbidity and mortality, as well as causing an inflammatory response which decreases the potency of opioid analgesia and possibly affects tolerance development. Therefore, we developed and validated a new method, intermittent lumbar puncture (Dautzenberg et al.), for the study of opioid analgesia and tolerance. Using this method, opioid tolerance was reliably induced without detectable morbidity. The dose of morphine needed to induce analgesia and tolerance using this method was about 100-fold lower than that required when using an intrathecal catheter. Only slight inflammation was found at the injection site, dissipated within seven mm. ^ DAMGO, an opioid μ receptor agonist, has been reported to inhibit morphine tolerance, but results from different studies are inconclusive. We evaluated the effect of DAMGO on morphine tolerance using our newly-developed ILP method, as well as other intrathecal catheter paradigms. We found that co-administration of sub-analgesic DAMGO with morphine using ILP did not inhibit morphine tolerance, but instead blocked the analgesic effects of morphine. Tolerance to morphine still developed. Tolerance to morphine can only be blocked by sub-analgesic dose of DAMGO when administered in a lumbar catheter, but not in cervical catheter settings. ^ Finally, we evaluated the effects of Gabapentin (GBP) on analgesia and morphine tolerance. We demonstrated that GBP enhanced analgesia mediated by both subanalgesic and analgesic doses of morphine although GBP itself was not analgesic. GBP increased potency and efficacy of morphine. GBP inhibited the expression, but not the development, of morphine tolerance. GBP blocked tolerance to analgesic morphine but not to subanalgesic morphine. GBP reversed the expression of morphine tolerance even after tolerance was established. These studies may begin to provide new insights into mechanisms of morphine tolerance development and improve clinical chronic pain management. ^

STUDIES ON CHOLINERGIC FUNCTION AND MEMORY IN MICE (CHOLINOTOXINS, WORKING, REFERENCE MEMORY, RADIAL ARM MAZE)

Considerable evidence suggests that central cholinergic neurons participate in either acquisition, storage or retrieval of information. Experiments were designed to evaluate information processing in mice following either reversible or irreversible impairment in central cholinergic activity. The cholinergic receptor antagonists, atropine and methylatropine were used to reversibly inhibit cholinergic transmission. Irreversible impairment in central cholinergic function was achieved by central administration of the cholinergic-specific neurotoxins, N-ethyl-choline aziridinium (ECA) and N-ethyl-acetylcholine aziridinium (EACA).^ ECA and EACA appear to act by irreversible inhibition of high affinity choline uptake (proposed rate-limiting step in acetylcholine synthesis). Intraventricular administration of ECA or EACA produced persistent reduction in hippocampal choline acetyltransferase activity. Other neuronal systems and brain regions showed no evidence of toxicity.^ Mice treated with either ECA or EACA showed behavioral deficits associated with cholinergic dysfunction. Passive avoidance behavior was significantly impaired by cholinotoxin treatment. Radial arm maze performance was also significantly impaired in cholinotoxin-treated animals. Deficits in radial arm maze performance were transient, however, such that rapid and apparent complete behavioral recovery was seen during retention testing. The centrally active cholinergic receptor antagonist atropine also caused significant impairment in radial arm maze behavior, while equivalent doses of methylatropine were without effect.^ The relative effects of cholinotoxin and receptor antagonist treatment on short-term (working) memory and long-term (reference) memory in radial arm maze behavior were examined. Maze rotation studies indicated that there were at least two different response strategies which could result in accurate maze performance. One strategy involved the use of response algorithms and was considered to be a function of reference memory. Another strategy appeared to be primarily dependent on spatial working memory. However, all behavioral paradigms with multiple trails have reference memory requirements (i.e. information useful over all trials). Performance was similarly affected following either cholinotoxin or anticholinergic treatment, regardless of the response strategy utilized. In addition, rates of behavioral recovery following cholinotoxin treatment were similar between response groups. It was concluded that both cholinotoxin and anticholinergic treatment primarily resulted in impaired reference memory processes. ^

REGULATION OF ALTERNATIVE CARBON METABOLISM IN CANDIDA ALBICANS

Candida albicans is the most important fungal pathogen of humans. Transcript profiling studies show that upon phagocytosis by macrophages, C. albicans undergoes a massive metabolic reorganization activating genes involved in alternative carbon metabolism, including the glyoxylate cycle, β-oxidation and gluconeogenesis. Mutations in key enzymes such as ICL1 (glyoxylate cycle) and FOX2 (fatty acid β-oxidation) revealed that alternative carbon metabolic pathways are required for full virulence in C. albicans. These studies indicate C. albicans uses non-preferred carbon sources allowing its adaptation to microenvironments were nutrients are scarce. It has become apparent that the regulatory networks required for regulation of alternative carbon metabolism in C. albicans are considerably different from the Saccharomyces cerevisiae paradigm and appear more analogous to the Aspergillus nidulans systems. Well-characterized transcription factors in S. cerevisiae have no apparent phenotype or are missing in C. albicans. CTF1 was found to be a single functional homolog of the A. nidulans FarA/FarB proteins, which are transcription factors required for fatty acid utilization. Both FOX2 and ICL1 were found to be part of a large CTF1 regulon. To increase our understanding of how CTF1 regulates its target genes, including whether regulation is direct or indirect, the FOX2 and ICL1 promoter regions were analyzed using a combination of bioinformatics and promoter deletion analysis. To begin characterizing the FOX2 and ICL1 promoters, 5’ rapid amplification of cDNA ends (5’RACE) was used to identify two transcriptional initiation sites in FOX2 and one in ICL1. GFP reporter assays show FOX2 and ICL1 are rapidly expressed in the presence of alternative carbon sources. Both FOX2 and ICL1 harbor the CCTCGG sequence known to be bound by the Far proteins, hence rendering the motif as a putative CTF1 DNA binding element. In this study, the CCTCGG sequence was found to be essential for FOX2 regulation. However, this motif does not appear to be equally important for the regulation of ICL1. This study supports the notion that although C. albicans has diverged from the paradigms of model fungi, C. albicans has made specific adaptations to its transcription-based regulatory network that may contribute to its metabolic flexibility.

Voces desde la historia : Ignacio Solares y la novela de la revolución mexicana

A partir de los nuevos paradigmas que conocemos como Novelas Históricas Posmodernas, el escritor mexicano retoma esa extensa línea temática que se origina en el acontecimiento histórico que convulsionó, a principios del siglo XX, la extensa geografía mexicana. El objetivo de este trabajo es abarcar el estudio de las tres novelas de Solares que se ocupan de textualizar episodios de la Revolución: Madero, el otro, de 1989, La noche de Ángeles, de 1991, Columbus, 1996. La elección de las figuras manifiesta la intención de devolverles su verdadera voz desde esa mirada que sólo permite la ficción, en tanto los hechos contados surgieron “más de lo simbólicamente verdadero que de lo históricamente exacto". La atención estará en destacar la presencia de voces que, desde una particular focalización, se ocuparán de insertar en el discurso modalizaciones diversas. Estas voces habrán de problematizar, con mayor o menor intensidad según los diversos registros, impugnando, cuestionando o rescatando ciertos actos oscuros del pasado, llevados a cabo por quienes protagonizaron la gesta revolucionaria. El tono apelativo característico explicita, por otra parte, el lugar desde el cual la historia debe ser leída.

Paradigmas de Estado en Brasil según Amado Cervo : una perspectiva desde el Sur Global

El artículo analiza la relevancia de estudiar la historia, la configuración y el rol que ha tenido el Estado en Brasil. El concepto de paradigma de Estado, que implica una nueva interpretación de la forma que adopta la economía y la sociedad con sus intereses, el patrón de inserción internacional y la formación nacional de cada etapa, es una herramienta conceptual propuesta por Amado Cervo, para comprender la interacción entre los factores internacionales y los condicionantes domésticos. Este autor sostiene la existencia de cuatro paradigmas: el liberal conservador, el desarrollista, el normal y el logístico.

Economía e ideología en el franquismo : tensiones entre utopía y pragmatismo 1945 -1970

El presente trabajo enfoca desde una perspectiva comparativa y analítica algunos aspectos de la economía y la sociedad españolas durante años especialmente interesantes de la dictadura franquista. Se efectúa una revisión de la ideología con la que el régimen pretendió encarar, a través de un proyecto autárquico, inicialmente muy marcado por el modelo fascista, el despegue económico de España y los virajes posteriores originados en las tensiones surgidas en el seno de la sociedad y de los paradigmas externos que marcaban el rumbo hacia una integración de bloques. Como fecha límite de este estudio se presentan los últimos años de la década del '60, puesto que parecen constituir el cierre de un ciclo. En cuestiones ideológico-políticas ese cierre estuvo signado por el ascenso del almirante Carrero Blanco a una posición clave y la sustitución de los viejos falangistas por un grupo más homogéneo de "tecnócratas" del capitalismo moderno. En materia económica también se completó entonces un período de crecimiento sin precedentes en la economía española que hacia 1973/74 entró en una meseta, parte de la crisis cíclica compartida por la economía mundial.

Paradigmas de interacción hombre-máquina : un análisis enfocado al ámbito de la educación especial

Este trabajo se enmarca en el área de interacción hombre-máquina y los diferentes paradigmas que existe actualmente. Serevisan antecedentes y posibilidades vinculadas a la educación especial. Comocaso de estudio, se presenta una propuesta de adaptación al software educativo JClic, mediante la utilización de comandos por voz, con el objetivo de ser utilizado por usuarios/alumnos con deficiencia motriz sin consecuencias o con consecuencias leves en el desarrollo del lenguaje. Como parte de esta propuesta de adaptación, se estudiaron diferentes motores de reconocimiento de voz (RV), y se profundizó el análisis del motor de RV Sphinx-4. Se presenta aquí parte de este trabajo realizado y los resultados y conclusiones obtenidas, luego de la evaluación del prototipo.

Diálogos entre feminismos y Buen Vivir/Vivir Bien : distintas perspectivas, múltiples puntos de encuentro

Este artículo surge del diálogo entre distintos saberes y conocimientos, con el objetivo de identificar principalmente las convergencias entre el Buen Vivir/Vivir Bien y los feminismos latinoamericanos. Iniciamos este trabajo considerando las ideas centrales del enfoque del Buen Vivir/Vivir Bien y sus mecanismos de traducción concreta en las reformas constitucionales de Bolivia y Ecuador. Luego, nos detenemos en las confluencias –aunque identificando algunas tensiones– entre esta última propuesta y los feminismos, haciendo foco en la dimensión económica. Y finalmente, reflexionamos sobre los aspectos nodales desarrollados en el trabajo, buscando, asimismo repensar el papel de las ciencias sociales a la luz de estas corrientes de pensamiento y de los procesos sociales contrahegemónicos.

Diseño e innovación : una visión sobre la industria del mueble mendocino

Se analizaron los procesos de cambio tecnológico en la industria del mueble en Mendoza, considerando el rol del diseño industrial. Ésta partió del supuesto que el diseño, la innovación y la tecnología se vinculan en este proceso. Sin embargo, el diseño ocupa un papel de escasa relevancia. El objetivo fue analizar el proceso de cambio tecnológico, teniendo en cuenta la incidencia de la innovación y en particular del diseño; analizar las políticas públicas provinciales dirigidas hacia este subsector. Metodológicamente se combinaron los paradigmas cuantitativo y cualitativo. Se pudo caracterizar el subsector y los empresarios de las empresas. Se espera que con los resultados puedan verse beneficiados organismos públicos y privados e instituciones académicas (UNCuyo), especialmente los dedicados a la vinculación con el medio productivo.

Sociología de la salud : políticas sociales y políticas de salud

Pretendemos en este artículo realizar una mirada desde la sociología de la salud. Nos interesa observar los enfoques que existen sobre ella. Conocemos con el nombre de modelo biomédico al que hegemónicamente está instalado en nuestras sociedades modernas. A su vez, es necesario establecer un contraste con la visión que tienen los pueblos originarios sobre la salud, una mirada sobre lo universal versus los particularismos de las identidades de estos pueblos, que tienen mucho para aportar en torno a la salud como valor universal. Abordamos también la relación con el modelo dominante de salud, visto desde la globalización y sus consecuentes paradigmas económicos y sociales, arraigados más bien en el neoliberalismo y que ejercieron un cambio sustancial en la atención de salud en América Latina. Su valor universal de la atención pública y su posible aplicación a través de las politicas públicas, responde a una lógica no del todo comprendida, por lo que a veces juzgamos más necesaria la atención privada. Sin quitar importancia a ésta, pretendemos abordar el sentido de la condicion humana, la expresión de lo universal relacionado con la distribución de la riqueza, el derecho de los ciudadanos y el rol que le cabe a la sociedad para lograr una salud que pueda llegar a todos. Así, a partir del mercado capitalista y su vinculación con el circuito económico global como el del consumo, vemos cómo se impone una lógica común,a saber: el ser humano como mercancía. La mirada sobre la naturaleza y a partir de ella, en los individuos, es fetichizada, es decir, no se muestra como tal, se esconde bajo otra cara en general. El mercado capitalista de la salud global, está afectando a las poblaciones cada vez en mayores dimensiones debido a la desigual distribución de la riqueza y al desplazamiento del estado en las políticas públicas.