Functional Upregulation of Ca2+ -Activated K+ Channels in the Development of Substantia Nigra Dopamine Neurons

Many connections in the basal ganglia are made around birth when animals are exposed to a host of new affective, cognitive, and sensori-motor stimuli. It is thought that dopamine modulates cortico-striatal synapses that result in the strengthening of those connections that lead to desired outcomes. We propose that there must be a time before which stimuli cannot be processed into functional connections, otherwise it would imply an effective link between stimulus, response, and reward in uterus. Consistent with these ideas, we present evidence that early in development dopamine neurons are electrically immature and do not produce high-frequency firing in response to salient stimuli. We ask first, what makes dopamine neurons immature? and second, what are the implications of this immaturity for the basal ganglia? As an answer to the first question, we find that at birth the outward current is small (3nS-V), insensitive to Ca2+, TEA, BK, and SK blockers. Rapidly after birth, the outward current increases to 15nS-V and becomes sensitive to Ca2+, TEA, BK, and SK blockers. We make a detailed analysis of the kinetics of the components of the outward currents and produce a model for BK and SK channels that we use to reproduce the outward current, and to infer the geometrical arrangement of BK and Ca2+ channels in clusters. In the first cluster, T-type Ca2+ and BK channels are coupled within distances of similar to 20 nm (200 parallel to). The second cluster consists of L-type Ca2+ and BK channels that are spread over distances of at least 60 nm. As for the second question, we propose that early in development, the mechanism of action selection is in a "locked-in" state that would prevent dopamine neurons from reinforcing cortico-striatal synapses that do not have a functional experiential-based value.

The work of psychologists in social policy in Brazil

This study verses on the meeting of psychology with the social policy area. The objective is to discuss how psychologists that work in the Basic Health Units and in the Social Assistance Reference Centers experience their daily practices. Using the interview and participant observation methods, we investigated the modes of action of 13 psychologists involved in these service units. The results indicate that because these contexts are adverse to the traditional forms of action, many professionals experience daily strangeness and discomfort, resulting from their encounters with limiting situations of difficult management. Furthermore, we observed practices and experiences that were marked by feelings of compassion, pity, and resentment. We consider, finally, that the encounter between psychology and social policies requires flexibility in traditional acting modes as well as the pursuit of strategies that consider cultural contexts characteristics, avoiding capture, fatigue and saturation process that stifle the worker.

Development and/or change of the notion of permanent object and operative causality: empirical evidence in the first year of life

This study examines the notion of permanent object during the first year of life, taking into account the controversy of two approaches about the nature of change: developmental change and cognitive change. Using a longitudinal/cross-sectional design, tasks adapted of the subscale of permanent object and operative causality of the Uzgiris-Hunt Scale (Uzgiris and Hunt, 1975) (Uzgiris & Hunt, 1975) were presented to 110 infants of 0, 3, 6 and 9 months-old, which reside in three cities of Colombia. The results showed three types of strategies: (a) Not resolution; (b) Exploratory and (c) Resolution, which follow different trajectories in children’s performance. This allows affirming that adaptive conquests of the cognitive development stay together with the variety of strategies. Using strategies reveals adjustments and transformations of action programs that consolidate the notion of permanent object not necessarily with age, but with self-regulatory processes. Empirical evidence contributes to the understanding of the relations between the emergence of novelty in the development and performance variability

Insurgency in a time of terrorism

Is it possible to separate terrorism from armed insurgency? Are all armed manifestations terrorism? Is terrorism a method of action or a logic for action? This article purports to analyze insurgency in the midst of the anti-terrorist era of the new century. By using Vietnam as an example, the author points out how armed insurgency has as of lately been called “terrorist”, yet stresses that this concept should be carefully and strategically looked through in order to better understand the violent nature of two very different phenomena: transactional and trans-national insurgencies-----¿Se puede escindir el terrorismo de la insurgencia armada? ¿Toda expresión armada es terrorismo? ¿El territorio es un método de acción o una lógica de acción? Este artículo presenta un análisis de la insurgencia a la luz de la era antiterrorista del nuevo siglo. Con la utilización del ejemplo de Vietnam el autor señala cómo la insurgencia armada ha sido señalada de “terrorista”; sin embargo, debe revisarse detenidamente de manera estratégica este concepto para entender mejor la naturaleza de la violencia de dos fenómenos diferentes: la insurgencia transnacional y el terrorismo transnacional.

I ara què? que hi ha en polítiques de joventut després del Plans de Joventut?

Fa més de 10 anys del primer Pla Nacional de Joventut de Catalunya, del pas de les polítiques de suport a l’associacionisme a les polítiques integrals, i amb aquestes la prolífica etapa dels Plans de Joventut i de l’expansió real de les polítiques de joventut al territori català. És a dia d’avui, en un moment de grans esdeveniments en aquest camp, en que es proposa un anàlisi sobre la futura evolució de les polítiques de joventut, basat en l’estudi i la interpretació de la informació existent i les aportacions de 9 persones vinculades al món de les polítiques de joventut

Theoretical studies of the exohedral reactivity of fullerene compounds

Des del descobriment del buckminster ful.lerè el 1985, s'ha despertat un interés enorme per entendre la reactivitat química així com les propietats d'aquests compostos. La funcionalització exoèdrica del ful.lerè més abundant, el C60, està força ben establerta. Tanmateix, la investigació en aquest camp encara continua oberta ja que s'han sintetitzat una gran varietat de derivats molt prometedors donades les seves futures aplicacions. La tesi comprèn quinze capítols que contenen set publicacions relacionades. Els primers dos estudis es basen en la reacció Diels-Alder sobre els anomenats metal.loful.lerens endoèdrics TNT X3N@C78, X= Sc, Y. Aquest projecte de investigació està motivat pel desconeixament existent sobre les possibles conseqüències de l'encapsulació del grup X3N. El tercer estudi descriu minuciosament els canvis detectats en la funcionalització exoèdrica un cop s'ha produït l'encapsulació dels diferents gasos nobles. En aquesta tesi s'estudia en detall l'ús de l'aproximació ONIOM per a estudiar reaccions de cicloaddició en compostos ful.lerènics. Els resultats d'aquest projecte són d'alt interès per a la realització dels estudis posteriors sobre la reacció de Diels-Alder i la 1,3-dipolar en ful.lerens i derivats. Finalment, l'última part d'aquesta tesi es basa en les propietats antioxidants de determinats ful.lerens. A l'últim treball inclòs en aquesta tesi s'estudia en detall el mecanismo de reacció per a la eliminació del ió superòxid en presència de ful.lerens.

Fire blight (Erwinia amylovora) of rosaceous plants. Pathogen virulence and selection and characterization of biological control agents

El fuego bacteriano, causado por Erwinia amylovora, es una enfermedad muy importante a nivel comercial y económico porque afecta a plantas de la familia de las rosáceas y es especialmente agresiva en manzano (Pyrus malus) y peral (Pyrus communis), así como en plantas ornamentales (Crataegus, Cotoneaster o Pyracantha). Esta enfermedad está distribuida por todo el mundo en zonas climáticas templadas de Amércia del Norte, Nueva Zelanda, Japón, Israel, Turquí y Europa. En España, el fuego bacteriano fue detectado por primera vez en 1995 en el norte del País (Euskadi) y más tarde en nuevos focos aparecidos en otras áreas. La enfermedad puede ser controlada comercialmente mediante la aplicación de pesticidas quimicos (derivados de cobre, antibioticos). Sin embargo, muchos de los productos químicos presentan baja actividad o causan fitotoxicidad, y la estreptomicina, el producto más eficaz, esta prohibido en muchos países, incluyendo España. Por tanto, en ausencia de apropiados agentes químicos, el control biológico se contempla como una buena alternativa. En el presente trabajo, un agente de control biológico, Pseudomonas fluorescens EPS62e, ha sido seleccionada de entre 600 aislados de las especies P. fluorescens y Pantoea agglomerans obtenidos de flores, frutos y hojas de plantas de la familia de las rosáceas durante una prospección llevada a cabo en varias áreas geográficas de España. La cepa ha sido seleccionada por su capacidad de suprimir la infecciones producidas por E. amylovora frutos inmaduros, flores y brotes de peral en condiciones de ambiente controlado, presentando unos niveles de control similares a los obtenidos mediante el control químico usando derivados de cobre o antibióticos. La cepa además ha mostrado la capacidad de colonizar y sobrevivir en flores y heridas producidas en frutos inmaduros en condiciones de ambiento controlado pero también en flores en condiciones de campo. La exclusión de E. amylovora medinate la colonización de la superficie, el consumo de nutrientes, y la interacción entre las células del patógeno y del agente de biocontrol es la principal causa de la inhibición del fuego bacteriano por la cepa EPS62e. Estas características constituyen aspectos interesantes para un desarrollo efectivo de la cepa EPS62e como un agente de biocontrol del fuego bacteriano en condiciones comerciales.

Autoavaliação de um agrupamento : um percurso de melhoria da qualidade de gestão e do serviço educativo da escola

Com o propósito de acompanhar a mudança da sociedade, em Portugal decorre a implementação de várias reformas entre as quais a da Administração Pública. Melhorar o serviço educativo prestado pelas escolas é condição essencial para o aumento da qualificação dos alunos. A Avaliação e a Auto Avaliação (AA) do desempenho da escola tornam-se cada vez mais importantes no sentido de acompanhar e garantir a evolução e o progresso do sistema educativo. Desta forma, torna-se imprescindível uma reflexão sobre os procedimentos desenvolvidos que visam suprir as necessidades das escolas. Este projeto de investigação, no âmbito do Mestrado em Ciências da Educação, especialização em Administração Escolar, tem como finalidade dar o seu contributo para esse debate, através da apresentação e discussão dos resultados de dois ciclos avaliativos, tendo sido aplicado, o modelo CAF (Common Assessment Framework). Neste sentido, pretendeu-se averiguar de que forma a AA (Auto Avaliação) contribui para o processo global de gestão da escola. Fazendo recurso à metodologia de estudo de caso, num Agrupamento de Escolas no interior do país, utilizou-se o paradigma qualitativo para a recolha de dados. Pela análise dos dados foi possível concluir que a aplicação do primeiro ciclo de avaliação, através do desenvolvimento de processos de melhoria da qualidade de serviço prestado, influenciou o segundo ciclo avaliativo. Esta influência foi evidente na melhoria dos planos de ação para colmatar pontos negativos detetados no ciclo avaliativo anterior contribuindo, consequentemente, para a melhoria do processo de gestão da escola. Desta forma, a experiência adquirida, as alterações introduzidas, a convição dos órgãos de gestão da escola e de quase todas as pessoas que nela exercem a sua atividade permitem concluir que é imprescindível a autorregulação e que a mesma proporcionou benefícios que levaram à melhoria da qualidade de gestão da escola.

The community museum: a space for the exercise of communal power

This paper discusses two key elements in the field of museums: a summary of the concept of the community museum, on the one hand, and, on the other, a proposal as to how this concept is put into practice, especially in the early stages of the creation of the museum, when the social basis for the project is being established. We will discuss how the community museum combines and integrates complex processes aimed at strengthening the community as a collective subject, asserting its identity, improving its quality of life and building alliances between communities. In the second part, which has a methodological focus, we will discuss how the museum is born out of community aspirations to strengthen its identity and integrity, the initial process of consensus-building, the roles of different agents, both internal and external to the community, as well as some factors that foster or prevent community appropriation. To conclude we will emphasize the potential of community museum networks as a strategy to generate a broader field of action, in which communities can exercise greater autonomy, by collectively developing and appropriating projects of regional and even international scope.

Investigation of the effects of the novel anticonvulsant compound carisbamate(RWJ-333369) on rat piriform cortical neurones in vitro

Background and purpose: Carisbamate is being developed for adjuvant treatment of partial onset epilepsy. Carisbamate produces anticonvulsant effects in primary generalized, complex partial and absence-type seizure models, and exhibits neuroprotective and antiepileptogenic properties in rodent epilepsy models. Phase IIb clinical trials of carisbamate demonstrated efficacy against partial onset seizures; however, its mechanisms of action remain unknown. Here, we report the effects of carisbamate on membrane properties, evoked and spontaneous synaptic transmission and induced epileptiform discharges in layer II-III neurones in piriform cortical brain slices. Experimental approach: Effects of carisbamate were investigated in rat piriform cortical neurones by using intracellular electrophysiological recordings. Key results: Carisbamate (50–400 mmol·L-1) reversibly decreased amplitude, duration and rise-time of evoked action potentials and inhibited repetitive firing, consistent with use-dependent Na+ channel block; 150–400 mmol·L-1 carisbamate reduced neuronal input resistance, without altering membrane potential. After microelectrode intracellular Cl- loading, carisbamate depolarized cells, an effect reversed by picrotoxin. Carisbamate (100–400 mmol·L-1) also selectively depressed lateral olfactory tract-afferent evoked excitatory synaptic transmission (opposed by picrotoxin), consistent with activation of a presynaptic Cl conductance. Lidocaine (40–320 mmol·L-1) mimicked carisbamate, implying similar modes of action. Carisbamate (300–600 mmol·L-1) had no effect on spontaneous GABAA miniature inhibitory postsynaptic currents and at lower concentrations (50–200 mmol·L-1) inhibited Mg2+-free or 4-aminopyridine-induced seizure-like discharges. Conclusions and implications: Carisbamate blocked evoked action potentials use-dependently, consistent with a primary action on Na+ channels and increased Cl- conductances presynaptically and, under certain conditions, postsynaptically to selectively depress excitatory neurotransmission in piriform cortical layer Ia-afferent terminals.

Development of multi-electrode array screening for anticonvulsants in acute rat brain slices

The acute hippocampal brain slice preparation is an important in vitro screening tool for potential anticonvulsants. Application of 4-aminopyridine (4-AP) or removal of external Mg2+ ions induces epileptiform bursting in slices which is analogous to electrical brain activity seen in status epilepticus states. We have developed these epileptiform models for use with multi-electrode arrays (MEAs), allowing recording across the hippocampal slice surface from 59 points. We present validation of this novel approach and analyses using two anticonvulsants, felbamate and phenobarbital, the effects of which have already been assessed in these models using conventional extracellular recordings. In addition to assessing drug effects on commonly described parameters (duration, amplitude and frequency), we describe novel methods using the MEA to assess burst propagation speeds and the underlying frequencies that contribute to the epileptiform activity seen. Contour plots are also used as a method of illustrating burst activity. Finally, we describe hitherto unreported properties of epileptiform bursting induced by 100M4-AP or removal of external Mg2+ ions. Specifically, we observed decreases over time in burst amplitude and increase over time in burst frequency in the absence of additional pharmacological interventions. These MEA methods enhance the depth, quality and range of data that can be derived from the hippocampal slice preparation compared to conventional extracellular recordings. It may also uncover additional modes of action that contribute to anti-epileptiform drug effects

The social relations of business representation and devolved governance in the United Kingdom

The reform of regional governance in the United Kingdom has been, in part, premised on the notion that regions provide new territories of action in which cooperative networks between business communities and state-agencies can be established. Promoting business interests is seen as one mechanism for enhancing the economic competitiveness and performance of 'laggard' regions. Yet, within this context of change, business agendas and capacities are often assumed to exist 'out there, as a resource waiting to be tapped by state institutions. There is little recognition that business organisations' involvement in networks of governance owes much to historical patterns and practices of business representation, to the types of activities that exist within the business sector, and to interpretations of their own role and position within wider policymaking and implementation networks. This paper, drawing on a study of business agendas in post-devolution Scotland, demonstrates that in practice business agendas are highly complex. Their formation in any particular place depends on the actions of reflexive agents, whose perspectives and capacities are shaped by the social, economic, and political contexts within which they are operating. As such, any understanding of business agendas needs to identify the social relations of business as a whole, rather than assuming away such complexities.

In search of simple structures in climate: Simplifying EOFs

Empirical orthogonal functions (EOFs) are widely used in climate research to identify dominant patterns of variability and to reduce the dimensionality of climate data. EOFs, however, can be difficult to interpret. Rotated empirical orthogonal functions (REOFs) have been proposed as more physical entities with simpler patterns than EOFs. This study presents a new approach for finding climate patterns with simple structures that overcomes the problems encountered with rotation. The method achieves simplicity of the patterns by using the main properties of EOFs and REOFs simultaneously. Orthogonal patterns that maximise variance subject to a constraint that induces a form of simplicity are found. The simplified empirical orthogonal function (SEOF) patterns, being more 'local'. are constrained to have zero loadings outside the main centre of action. The method is applied to winter Northern Hemisphere (NH) monthly mean sea level pressure (SLP) reanalyses over the period 1948-2000. The 'simplified' leading patterns of variability are identified and compared to the leading patterns obtained from EOFs and REOFs. Copyright (C) 2005 Royal Meteorological Society.

Omega-3 fatty acids, cardiovascular disease and stability of atherosclerotic plaques

Long-chain n-3 polyunsaturated fatty acids are found in oily fish and in fish oils and similar preparations. Substantial evidence from epidemiological and case-control studies indicates that consumption of fish, oily fish and long-chain n-3 fatty acids reduces risk of cardiovascular mortality. Secondary prevention studies using long-chain n-3 fatty acids in patients post-myocardial infarction have shown a reduction in total and cardiovascular mortality with an especially potent effect on sudden death. Long-chain n-3 fatty acids have been shown to beneficially modify a range of cardiovascular risk factors, which may result in primary cardiovascular prevention. However, reduced non-fatal and fatal events and a reduction in sudden death probably involve other mechanisms. Reduced thrombosis following long-chain n-3 fatty acids may play a role. A decrease in arrhythmias is a favoured mechanism of action of long-chain n-3 fatty acids and is supported by cell culture and animal studies. However human trials using implantable cardiac defibrillators have produced inconsistent findings and a recent meta-analysis does not support this mechanism of action. An alternative mechanism of action may be stabilisation of atherosclerotic plaques by long-chain n-3 fatty acids. This is suggested by one published human study which showed that incorporation of long-chain n-3 fatty acids into plaques collected at carotid endarterectomy resulted in fewer macrophages in the plaque and a morphology indicative of increased stability. These findings are supported from observations in an animal model and suggest that the primary effect of long-chain n-3 fatty acids might be on macrophages within the plaque.