La Ordenación del Territorio en las Ciudades Globales Europeas: El caso de Madrid

En la Comunidad de Madrid el modelo de ocupación del territorio en las dos últimas décadas ha obedecido a factores de oferta del mercado y no a las necesidades de la población, ello provoca un consumo de suelo y de recursos que conducen a una sobrexplotación insostenible. Las metrópolis globales están experimentando rápidas e intensas transformaciones, basadas en los paradigmas emergentes de la globalización, la gobernanza, la metropolizacion y la dispersión de las actividades en el territorio y a través de ellos se abordan los planes de Londres, París y las tentativas de Madrid. La globalización provoca la pérdida de soberanía de las administraciones publicas y la competitividad entre las ciudades globales en Europa, Londres, Paris y Madrid, son centros de poder, de concentración y crecimiento donde se produce la dualización del espacio y donde la desigualdad participa de la restructuración urbana, concentración de pobreza frente a espacios de la nueva clase emergente en donde dominan los sectores de servicios y las tecnologías de la información. Frente al desarrollo urbano neoliberal de regulación a través del mercado y basada en criterios de eficiencia de la Nueva Gestión Pública, se vislumbra la posibilidad de que la sociedad se administre a si misma por medio de acciones voluntarias y responsables que promuevan los intereses colectivos mediante el reconocimiento de su propia identidad, introduciendo el concepto de gobernanza. Frente, a la explotación del territorio por parte de la sociedad extractiva que genera corrupcion, se propone un modelo de cooperación público-privada basado en la confianza mutua, un marco regulador estable, la transparencia y la información a cuyo flujo más homogéneo contribuirán sin duda las TICs. En todo este proceso, las regiones metropolitanas en Europa se erigen como motores del crecimiento, donde los límites administrativos son superados, en un territorio cada vez más extendido y donde los gobiernos locales tienen que organizarse mediante un proceso de cooperación en la provisión de servicios que ayuden a evitar los desequilibrios territoriales. El fenómeno de la dispersión urbana en desarrollos de baja densidad, los centros comerciales periféricos, la expulsión hacia la periferia de las actividades de menor valor añadido y la concentración de funciones directivas en el centro, conducen a una fragmentación del territorio en islas dependientes del automóvil y a procesos de exclusión social por la huida de las rentas altas y la expulsión de las rentas bajas de los centros urbanos. Se crean fragmentos monofuncionales y discontinuos, apoyados en las autovías, lugares carentes de identidad y generadores de despilfarro de recursos y una falta de sostenibilidad ambiental, económica y social. El estudio de la cultura de la planificación en Europa ayuda a comprender los diferentes enfoques en la ordenación del territorio y el proceso de convergencia entre las diferentes regiones. Los documentos de la UE se basan en la necesidad de la competitividad para el crecimiento europeo y la cohesión social y en relación al territorio en los desarrollos policéntricos, la resolución del dualismo campo-ciudad, el acceso equilibrado a las infraestructuras, la gestión prudente de la naturaleza, el patrimonio y el fomento de la identidad. Se proponen dos niveles de estudio uno actual, los últimos planes de Londres y Paris y el otro la evolución de las tentativas de planes en la Región madrileña siempre en relación a los paradigmas emergentes señalados y su reflejo en los documentos. El Plan de Londres es estratégico, con una visión a largo plazo, donde se confiere un gran interés al proceso, al papel del alcalde como líder y su adaptación a las circunstancias cambiantes, sujeto a las incertidumbres de una ciudad global. El desarrollo del mismo se concibe a través de la colaboración y cooperación entre las administraciones y actores. La estructura del documento es flexible, establece orientaciones y guías indicativas, para la redacción de los planes locales, no siendo las mismas vinculantes y con escasa representación grafica. El Plan de París es más un plan físico, similar al de otros centros europeos, trabaja sobre los sectores y sobre los territorios, con información extensa, con características de “Plan Latino” por la fuerza de la expresión gráfica, pero al mismo tiempo contiene una visión estratégica. Es vinculante en sus determinaciones y normativas, se plantea fomentar, pero también prohibir. Ambos planes tratan la competitividad internacional de sus centros urbanos, la igualdad social, la inclusión de todos los grupos sociales y la vivienda como una cuestión de dignidad humana. Londres plantea la gobernanza como cooperación entre sector público-privado y la necesaria cooperación con las regiones limítrofes, en París las relaciones están más institucionalizadas resaltando la colaboración vertical entre administraciones. Ambos plantean la densificación de nodos servidos por transporte público, modos blandos y el uso los TODs y la preservación de la infraestructura verde jerarquizada, la potenciación de la red azul y la mejora del paisaje de las periferias. En las “tentativas” de planes territoriales de Madrid se constata que estuvieron sujetas a los ciclos económicos. El primer Documento las DOT del año 1984, no planteaba crecimiento, ni económico ni demográfico, a medio plazo y por ello no proponía una modificación del modelo radio concéntrico. Se trataba de un Plan rígido volcado en la recuperación del medio rural, de la ciudad, el dimensionamiento de los crecimientos en función de las dotaciones e infraestructuras existentes. Aboga por la intervención de la administración pública y la promoción del pequeño comercio. Destaca el desequilibrio social en función de la renta, la marginación de determinados grupos sociales, el desequilibrio residencia/empleo y la excesiva densidad. Incide en la necesidad de viviendas para los más desfavorecidos mediante el alquiler, la promoción suelo público y la promoción del ferrocarril para dar accesibilidad al espacio central. Aboga por el equipamiento de proximidad y de pequeño tamaño, el tratamiento paisajístico de los límites urbanos de los núcleos y el control de las actividades ilegales señalando orientaciones para el planeamiento urbano. Las Estrategias (1989) contienen una visión: la modificación del modelo territorial, mediante la intervención pública a través de proyectos. Plantea la reestructuración económica del territorio, la reconversión del aparato productivo, la deslocalización de actividades de escaso valor añadido y una mayor ubicuidad de la actividad económica. Incide en la difusión de la centralidad hacia el territorio del sur, equilibrándolo con el norte, tratando de recomponer empleo y residencia, integrando al desarrollo económico las periferias entre sí y con el centro. Las actuaciones de transporte consolidarían las actuaciones, modificando el modelo radio concéntrico facilitando la movilidad mediante la red de cercanías y la intermodalidad. El plan se basaba en el liderazgo del Consejero, no integrando sectores como el medio ambiente, ni estableciendo un documento de seguimiento de las actuaciones que evaluara los efectos de las políticas y su aportación al equilibrio territorial, a través de los proyectos realizados. El Documento Preparatorio de las Bases (1995), es más de un compendio o plan de planes, recoge análisis y propuestas de los documentos anteriores y de planes sectoriales de otros departamentos. Presenta una doble estructura: un plan físico integrador clásico, que abarca los sectores y territorios, y recoge las Estrategias previas añadiendo puntos fuertes, como el malestar urbano y la rehabilitación el centro. Plantea la consecución del equilibrio ambiental mediante el crecimiento de las ciudades existentes, la vertebración territorial basada en la movilidad y en la potenciación de nuevas centralidades, la mejora de la habitabilidad y rehabilitación integral del Centro Urbano de Madrid, y la modernización del tejido productivo existente. No existe una idea-fuerza que aglutine todo el documento, parte del reconocimiento de un modelo existente concentrado y congestivo, un centro urbano dual y dos periferias al este y sur con un declive urbano y obsolescencia productiva y al oeste y norte con una dispersión que amenaza al equilibrio medioambiental. Señala como aspectos relevantes, la creciente polarización y segregación social, la deslocalización industrial, la aparición de las actividades de servicios a las empresas instaladas en las áreas metropolitanas, y la dispersión de las actividades económicas en el territorio por la banalización del uso del automóvil. Se plantea el reto de hacer ciudad de la extensión suburbana y su conexión con el sistema metropolitano, mediante una red de ciudades integrada y complementaria, en búsqueda de un mayor equilibrio y solidaridad territorial. Las Bases del PRET (1997) tenían como propósito iniciar el proceso de concertación en que debe basarse la elaboración del Plan. Parte de la ciudad mediterránea compacta, y diversa, y de la necesidad de que las actividades económicas, los servicios y la residencia estén en proximidad, resolviéndolo mediante una potente red de transporte público que permitiese una accesibilidad integrada al territorio. El flujo de residencia hacia la periferia, con un modelo ajeno de vivienda unifamiliar y la concentración del empleo en el centro producen desequilibrio territorial. Madrid manifiesta siempre apostó por la densificación del espacio central urbanizado, produciendo su congestión, frente al desarrollo de nuevos suelos que permitieran su expansión territorial. Precisa que es necesario preservar los valores de centralidad de Madrid, como generador de riqueza, canalizando toda aquella demanda de centralidad, hacia espacios más periféricos. El problema de la vivienda no lo ve solo como social, sino como económico, debido a la pérdida de empleos que supone su paralización. Observa ya los crecimientos residenciales en el borde de la region por el menor valor del suelo. Plantea como la política de oferta ha dado lugar a un modelo de crecimiento fragmentado, desequilibrado, desestructurado, con fuertes déficits dotacionales y de equipamiento, que inciden en la segregación espacial de las rentas, agravando el proceso de falta de identidad morfológica y de desarraigo de los valores urbanos. El plan señalaba que la presión sobre el territorio creaba su densificación por las limitaciones de espacio, Incidía en limitar el peso de la intervención pública, no planteando propuestas de cooperación público-privado. La mayor incoherencia estriba en que los objetivos eran innovadores y coinciden en su mayoría con las propuestas estudiadas de Londres o Paris, pero se intentan implementar a través de un cambio hacia un modelo reticulado homogéneo, expansivo sobre el territorio, que supone un consumo de suelo y de infraestructuras para solucionar un problema inexistente, la gestión de la densidad. Durante las dos últimas décadas en ausencia de un plan regional, la postura neoliberal fue la de un exclusivo control de legalidad del planeamiento, los municipios entraron en un proceso de competencia para aprovechar las iniciales ventajas económicas de los crecimientos detectados, que proporcionaban una base económica “sólida” a unos municipios con escasos recursos en sus presupuestos municipales. La legislación se modifica a requerimiento de grupos interesados, no existiendo un marco estable. Se pierde la figura del plan no solo a nivel regional, si no en los sectores y el planeamiento municipal donde los municipios tiende a basarse en modificaciones puntuales con la subsiguiente pérdida del modelo urbanístico. La protección ambiental se estructura mediante un extenso nivel de figuras, con diversidad de competencias que impide su efectiva protección y control. Este proceso produce un despilfarro en la ocupación del suelo, apoyada en las infraestructuras viarias, y un crecimiento disperso y de baja densidad, cada vez más periférico, produciéndose una segmentación social por dualización del espacio en función de niveles de renta. Al amparo del boom inmobiliario, se produce una falta de política social de vivienda pública, más basada en la dinamización del mercado con producción de viviendas para rentas medias que en políticas de alquiler para determinados grupos concentrándose estas en los barrios desfavorecidos y en la periferia sur. Se produce un incremento de la vivienda unifamiliar, muchas veces amparada en políticas públicas, la misma se localiza en el oeste principalmente, en espacios de valor como el entorno del Guadarrama o con viviendas más baratas por la popularización de la tipología en la frontera de la Región. El territorio se especializa a modo de islas monofuncionales, las actividades financieras y de servicios avanzados a las empresas se localizan en el norte y oeste próximo, se pierde actividad industrial que se dispersa más al sur, muchas veces fuera de la región. Se incrementan los grandes centros comerciales colgados de las autovías y sin población en su entorno. Todo este proceso ha provocado una pérdida de utilización del transporte público y un aumento significativo del uso del vehículo privado. En la dos últimas décadas se ha producido en la región de Madrid desequilibrio territorial y segmentación social, falta de implicación de la sociedad en el territorio, dispersión del crecimiento y un incremento de los costes ambientales, sociales y económicos, situación, que solo, a través del uso racional del territorio se puede reconducir, apoyado en una planificación integrada sensible y participativa. ABSTRACT In Madrid the model of land occupation in the past two decades has been driven by market supply factors rather than the needs of the population. This results in a consumption of land and resources that leads to unsustainable overexploitation. Addressing this issue must be done through sensitive and participatory integrated planning. Global cities are experiencing rapid and intense change based on the emerging paradigms of globalization, governance, metropolization and the dispersion of activities in the territory. Through this context, a closer look will be taken at the London and Paris plans as well as the tentative plans of Madrid. Globalization causes the loss of state sovereignty and the competitiveness among global cities in Europe; London, Paris and Madrid. These are centres of power, concentration and growth where the duality of space is produced, and where inequality plays a part in urban restructuration. There are concentrated areas of poverty versus areas with a new emerging class where the services sector and information technologies are dominant. The introduction of ICTs contributes to a more homogeneous flow of information leading, us to the concept of governance. Against neoliberal urban development based on free market regulations and efficiency criteria as established by the “New Public Management”, emerge new ways where society administers itself through voluntary and responsible actions to promote collective interests by recognizing their own identity. A new model of public-private partnerships surfaces that is based on mutual trust, transparency, information and a stable regulatory framework in light of territorial exploitation by the “extractive society” that generates corruption. Throughout this process, European metropolitan regions become motors of growth where administrative boundaries are overcome in an ever expanding territory where government is organized through cooperative processes to provide services that protect against regional imbalances. Urban sprawl or low-density development as seen in peripheral shopping centres, the off-shoring of low added-value activities to the periphery, and the concentration of business and top management functions in the centre, leads to a fragmentation of the territory in automobile dependent islands and a process of social exclusion brought on by the disappearance of high incomes. Another effect is the elimination of low income populations from urban centres. In consequence, discontinuous expansions and mono-functional places that lack identity materialize supported by a highway network and high resource consumption. Studying the culture of urban planning in Europe provides better insight into different approaches to spatial planning and the process of convergence between different regions. EU documents are based on the need of competitiveness for European growth and social cohesion. In relation to polycentric development territory they are based on a necessity to solve the dualism between field and city, balanced access to infrastructures, prudent management of nature and solidifying heritage and identity Two levels of study unfold, the first being the current plans of London and Île-de-France and the second being the evolution of tentative plans for the Madrid region as related to emerging paradigms and how this is reflected in documents. The London Plan is strategic with a long-term vision that focuses on operation, the role of the mayor as a pivotal leader, and the adaptability to changing circumstances brought on by the uncertainties of a global city. Its development is conceived through collaboration and cooperation between governments and stakeholders. The document structure is flexible, providing guidance and indicative guidelines on how to draft local plans so they are not binding, and it contains scarce graphic representation. The Plan of Paris takes on a more physical form and is similar to plans of other European centres. It emphasizes sectors and territories, using extensive information, and is more characteristic of a “Latin Plan” as seen in its detailed graphic expression. However, it also contains a strategic vision. Binding in its determinations and policy, it proposes advancement but also prohibition. Both plans address the international competitiveness of urban centres, social equality, inclusion of all social groups and housing as issues of human dignity. London raises governance and cooperation between public and private sector and the need for cooperation with neighbouring regions. In Paris, the relations are more institutionalized highlighting vertical collaboration between administrations. Both propose nodes of densification served by public transportation, soft modes and the use of TOD, the preservation of a hierarchical green infrastructure, and enhancing the landscape in urban peripheries. The tentative territorial plans for the Madrid region provide evidence that they were subject to economic cycles. The first document of master guidelines (1984) does not address either economic or demographic growth in the mid term and therefore does not propose the modification of the radio-concentric model. It is a rigid plan focused on rural and urban recovery and the dimensioning of growth that depends on endowments and infrastructures. It advocates government intervention and promotes small business. The plan emphasizes social imbalance in terms of income, marginalization of certain social groups, the imbalance of residence/employment and excessive density. It stresses the need for social rent housing for the underprivileged, promotes public land, and the supports rail accessibility to the central area. It backs facilities of proximity and small size, enhancing the landscaping of city borders, controlling illegal activities and draws out guidelines for urban planning. The strategies (1989) contain a vision: Changing the territorial model through public intervention by means of projects. They bring to light economic restructuring of territory, the reconversion of the productive apparatus, relocation of low value-added activities, and greater ubiquity of economic activity. They also propose the diffusion of centrality towards southern territories, balancing it with the north in an attempt to reset employment and residence that integrates peripheral economic development both in the periphery and the centre. Transport would consolidate the project, changing the radius-concentric model and facilitating mobility through a commuter and inter-modality network. The plan derives itself from the leadership of the minister and does not integrate sectors such as environment. It also does not incorporate the existence of a written document that monitors performance to evaluate the effects of policies and their contribution to the territorial balance. The Preparatory Document of the Bases, (1995) is more a compendium, or plan of plans, that compiles analysis and proposals from previous documents and sectorial plans from other departments. It has a dual structure: An integrating physical plan covering the sectors and territories that includes the previous strategies while adding some strengths. One such point is the urban discomfort and the rehabilitation of the centre. It also poses the achievement of environmental balance through the growth of existing cities, the territorial linking based on mobility, strengthening new centres, improving the liveability and comprehensive rehabilitation of downtown Madrid, and the modernization of the existing production network. There is no one powerful idea that binds this document. This is due to the recognition of an existing concentrate and congestive model, a dual urban centre, two eastern and southern suburbs suffering from urban decay, and an obsolescent productive north and west whose dispersion threatens the environmental balance. Relevant aspects the document highlights are increasing polarization and social segregation, industrial relocation, the emergence of service activities to centralized companies in metropolitan areas and the dispersion of economic activities in the territory by the trivialization of car use. It proposes making the city from the suburban sprawl and its connection to the metropolitan system through a network of integrated and complementary cities in search of a better balance and territorial solidarity. The Bases of PRET (1997) aims to start the consultation process that must underpin the development of the plan. It stems from a compact and diverse Mediterranean city along with the need for economic activities, services and residences that are close. To resolve the issue, it presents a powerful network of public transport that allows integrated accessibility to the territory. The flow of residence to the periphery based on a foreign model of detached housing and an employment concentration in the centre produces territorial imbalance. Madrid always opted for the densification of the central space, producing its congestion, against the development of new land that would allow its territorial expansion. The document states that the necessity to preserve the values of the housing problem is not only viewed as social, but also economic due to the loss of jobs resulting from their paralysis. It notes the residential growth in the regional border due to the low price of land and argues that the policy of supply has led to a fragmented model of growth that is unbalanced, unstructured, with strong infrastructure and facility deficits that affect the spatial segregation of income and aggravate the lack of morphological identity, uprooting urban values. The pressure on the territory caused its densification due to space limitation; the proposed grid model causes land consumption and infrastructure to solve a non-problem, density. Focusing on limiting the weight of public intervention, it does not raise proposals for public-private cooperation. The biggest discrepancy is that the targets were innovative and mostly align with the proposals in London and Paris. However, it proposes to be implemented through a shift towards a uniform gridded model that is expansive over territory. During the last two decades, due to the absence of a regional plan, a neoliberal stance held exclusive control of the legality of urban planning. The municipalities entered a competition process to take advantage of initial economic benefits of such growth. This provided a “solid” economic base for some municipalities with limited resources in their municipal budgets. The law was amended without a legal stable framework at the request of stakeholders. The character of the plan is lost not only regionally, but also in the sectors and municipal planning. This tends to be based on specific changes with the loss of an urban model. Environmental protection is organized through an extensive number of protection figures with diverse competencies that prevent its effective protection. This process squanders the use of the land, backed by increasing road infrastructure, dispersed occupations with low-density growth causing a social segmentation due to space duality based on income levels. During the housing boom, there is a reduction in social public housing policy mostly due to a boost in the market of housing production for average incomes than in rental policies for needy social groups that focus on disadvantaged neighbourhoods and southern suburbs. As a result, there is an increase in single-family housing, often protected by public policy. This is located primarily in the west in areas of high environmental value such as Guadarrama. There is also cheaper housing due to the popularization of typology in the border region. There, territory works as a mono-functional islands. Financial activities and advanced services for companies are located to the north and west where industrial activity is lost as it migrates south, often outside the region. The number of large shopping centres hanging off the highway infrastructure with little to no surrounding population increases. This process leads to the loss of dependency on public transport and a significant increase in the use of private vehicles. The absence of regional planning has produced more imbalance, more social segmentation, more dispersed growth and a lot of environmental, social and economic costs that can only be redirected through rational territorial.

ASPECTOS PSICODINÂMICOS E ADAPTATIVOS DE PAIS E MÃES DE CRIANÇAS DIAGNOSTICADAS COM PARALISIA CEREBRAL

Diante do sofrimento e das questões enfrentadas por pais e mães de crianças diagnosticadas com paralisia cerebral, o presente trabalho estudou aspectos psicodinâmicos e adaptativos. Para tanto, foi realizado estudo clínico, de recorte diagnóstico, em que participaram dois pais e duas mães de crianças com paralisia cerebral que contavam de 1 a 5 anos de idade. Os pais e mães passaram por entrevistas clínicas preventivas orientadas pela EDAO e pela técnica de Desenho-Estória com Tema. A análise do material obtido indicou que todos eles passaram por período de crise após a notícia do diagnóstico da criança e, na atualidade, foram classificados como tendo Adaptação Ineficaz, sendo que os dois pais e uma mãe tinham Adaptação Ineficaz Severa, uma mãe Adaptação Ineficaz Moderada. Com relação aos aspectos intra-píquicos, foram identificadas defesas primitivas nessa lida com o sofrimento ocasionado pela deficiência da criança. Concluiu-se que os recursos internos anteriores ao nascimento da criança e à própria personalidade de cada pai/mãe foi preponderante em sua adaptação e que a paralisia cerebral da criança afetou todos os setores adaptativos dos pais e mães.(AU)

ASPECTOS PSICODINÂMICOS E ADAPTATIVOS DE PAIS E MÃES DE CRIANÇAS DIAGNOSTICADAS COM PARALISIA CEREBRAL

Diante do sofrimento e das questões enfrentadas por pais e mães de crianças diagnosticadas com paralisia cerebral, o presente trabalho estudou aspectos psicodinâmicos e adaptativos. Para tanto, foi realizado estudo clínico, de recorte diagnóstico, em que participaram dois pais e duas mães de crianças com paralisia cerebral que contavam de 1 a 5 anos de idade. Os pais e mães passaram por entrevistas clínicas preventivas orientadas pela EDAO e pela técnica de Desenho-Estória com Tema. A análise do material obtido indicou que todos eles passaram por período de crise após a notícia do diagnóstico da criança e, na atualidade, foram classificados como tendo Adaptação Ineficaz, sendo que os dois pais e uma mãe tinham Adaptação Ineficaz Severa, uma mãe Adaptação Ineficaz Moderada. Com relação aos aspectos intra-píquicos, foram identificadas defesas primitivas nessa lida com o sofrimento ocasionado pela deficiência da criança. Concluiu-se que os recursos internos anteriores ao nascimento da criança e à própria personalidade de cada pai/mãe foi preponderante em sua adaptação e que a paralisia cerebral da criança afetou todos os setores adaptativos dos pais e mães.(AU)

Synaptic vesicle endocytosis mediates the entry of tetanus neurotoxin into hippocampal neurons

Tetanus neurotoxin causes the spastic paralysis of tetanus by blocking neurotransmitter release at inhibitory synapses of the spinal cord. This is due to the penetration of the toxin inside the neuronal cytosol where it cleaves specifically VAMP/synaptobrevin, an essential component of the neuroexocytosis apparatus. Here we show that tetanus neurotoxin is internalized inside the lumen of small synaptic vesicles following the process of vesicle reuptake. Vesicle acidification is essential for the toxin translocation in the cytosol, which results in the proteolytic cleavage of VAMP/synaptobrevin and block of exocytosis.

Kinesin-II Is Preferentially Targeted to Assembling Cilia and Is Required for Ciliogenesis and Normal Cytokinesis in TetrahymenaV⃞

We cloned two genes, KIN1 and KIN2, encoding kinesin-II homologues from the ciliate Tetrahymena thermophila and constructed strains lacking either KIN1 or KIN2 or both genes. Cells with a single disruption of either gene showed partly overlapping sets of defects in cell growth, motility, ciliary assembly, and thermoresistance. Deletion of both genes resulted in loss of cilia and arrests in cytokinesis. Mutant cells were unable to assemble new cilia or to maintain preexisting cilia. Double knockout cells were not viable on a standard medium but could be grown on a modified medium on which growth does not depend on phagocytosis. Double knockout cells could be rescued by transformation with a gene encoding an epitope-tagged Kin1p. In growing cells, epitope-tagged Kin1p preferentially accumulated in cilia undergoing active assembly. Kin1p was also detected in the cell body but did not show any association with the cleavage furrow. The cell division arrests observed in kinesin-II knockout cells appear to be induced by the loss of cilia and resulting cell paralysis.

Cytoplasmic Dynein, the Dynactin Complex, and Kinesin Are Interdependent and Essential for Fast Axonal Transport

In axons, organelles move away from (anterograde) and toward (retrograde) the cell body along microtubules. Previous studies have provided compelling evidence that conventional kinesin is a major motor for anterograde fast axonal transport. It is reasonable to expect that cytoplasmic dynein is a fast retrograde motor, but relatively few tests of dynein function have been reported with neurons of intact organisms. In extruded axoplasm, antibody disruption of kinesin or the dynactin complex (a dynein activator) inhibits both retrograde and anterograde transport. We have tested the functions of the cytoplasmic dynein heavy chain (cDhc64C) and the p150Glued (Glued) component of the dynactin complex with the use of genetic techniques in Drosophila. cDhc64C and Glued mutations disrupt fast organelle transport in both directions. The mutant phenotypes, larval posterior paralysis and axonal swellings filled with retrograde and anterograde cargoes, were similar to those caused by kinesin mutations. Why do specific disruptions of unidirectional motor systems cause bidirectional defects? Direct protein interactions of kinesin with dynein heavy chain and p150Glued were not detected. However, strong dominant genetic interactions between kinesin, dynein, and dynactin complex mutations in axonal transport were observed. The genetic interactions between kinesin and either Glued or cDhc64C mutations were stronger than those between Glued and cDhc64C mutations themselves. The shared bidirectional disruption phenotypes and the dominant genetic interactions demonstrate that cytoplasmic dynein, the dynactin complex, and conventional kinesin are interdependent in fast axonal transport.

Ion channel genes and human neurological disease: Recent progress, prospects, and challenges

What do epilepsy, migraine headache, deafness, episodic ataxia, periodic paralysis, malignant hyperthermia, and generalized myotonia have in common? These human neurological disorders can be caused by mutations in genes for ion channels. Many of the channel diseases are “paroxysmal disorders” whose principal symptoms occur intermittently in individuals who otherwise may be healthy and active. Some of the ion channels that cause human neurological disease are old acquaintances previously cloned and extensively studied by channel specialists. In other cases, however, disease-gene hunts have led the way to the identification of new channel genes. Progress in the study of ion channels has made it possible to analyze the effects of human neurological disease-causing channel mutations at the level of the single channel, the subcellular domain, the neuronal network, and the behaving organism.

Essential roles for four cytoplasmic intermediate filament proteins in Caenorhabditis elegans development

The structural proteins of the cytoplasmic intermediate filaments (IFs) arise in the nematode Caenorhabditis elegans from eight reported genes and an additional three genes now identified in the complete genome. With the use of double-stranded RNA interference (RNAi) for all 11 C. elegans genes encoding cytoplasmic IF proteins, we observe phenotypes for the five genes A1, A2, A3, B1, and C2. These range from embryonic lethality (B1) and embryonic/larval lethality (A3) to larval lethality (A1 and A2) and a mild dumpy phenotype of adults (C2). Phenotypes A2 and A3 involve displaced body muscles and paralysis. They probably arise by reduction of hypodermal IFs that participate in the transmission of force from the muscle cells to the cuticle. The B1 phenotype has multiple morphogenetic defects, and the A1 phenotype is arrested at the L1 stage. Thus, at least four IF genes are essential for C. elegans development. Their RNAi phenotypes are lethal defects due to silencing of single IF genes. In contrast to C. elegans, no IF genes have been identified in the complete Drosophila genome, posing the question of how Drosophila can compensate for the lack of these proteins, which are essential in mammals and C. elegans. We speculate that the lack of IF proteins in Drosophila can be viewed as cytoskeletal alteration in which, for instance, stable microtubules, often arranged as bundles, substitute for cytoplasmic IFs.

Cyp1a2(-/-) null mutant mice develop normally but show deficient drug metabolism.

Cytochrome P450 1A2 (CYP1A2) is a predominantly hepatic enzyme known to be important in the metabolism of numerous foreign chemicals of pharmacologic, toxicologic, and carcinogenic significance. CYP1A2 substrates include aflatoxin B1, acetaminophen, and a variety of environmental arylamines. To define better the developmental and metabolic functions of this enzyme, we developed a CYP1A2-deficient mouse line by homologous recombination in embryonic stem cells. Mice homozygous for the targeted Cyp1a2 gene, designated Cyp1a2(-/-), are completely viable and fertile; histologic examination of 15-day embryos, newborn pups, and 3-week-old mice revealed no abnormalities. No CYP1A2 mRNA was detected by Northern blot analysis. Moreover, mRNA levels of Cyp1a1, the other gene in the same subfamily, appear unaffected by loss of the Cyp1a2 gene. Because the muscle relaxant zoxazolamine is a known substrate for CYP1A2, we studied the Cyp1a2(-/-) genotype by using the zoxazolamine paralysis test: the Cyp1a2(-/-) mice exhibited dramatically lengthened paralysis times relative to the Cyp1a2(+/+) wild-type animals, and the Cyp1a2(+/-) heterozygotes showed an intermediate effect. Availability of a viable and fertile CYP1A2-deficient mouse line will provide a valuable tool for researchers wishing to define the precise role of CYP1A2 in numerous metabolic and pharmacokinetic processes.

Accelerated induction of experimental allergic encephalomyelitis in PL/J mice by a non-V beta 8-specific superantigen.

Superantigens such as the staphylococcal enterotoxins can play an important role in exacerbation of autoimmune disorders such as experimental allergic encephalomyelitis (EAE) in mice. In fact, superantigens can reactivate EAE in PL/J mice that have been sensitized to rat myelin basic protein (MBP). The T-cell subset predominantly responsible for disease in PL/J mice bears the V beta 8+ T-cell antigen receptor (TCR). The question arises as to whether T cells bearing other V beta specificities are involved in induction or reactivation of EAE with superantigen. Thus, we have investigated the ability of a non-V beta 8-specific superantigen, staphylococcal enterotoxin A (SEA) (V beta specificities 1, 3, 10, 11, and 17), to induce EAE in PL/J mice that have been previously protected from disease by anergy and deletion of V beta 8+ T cells. PL/J mice were first pretreated with the V beta 8-specific superantigen staphylococcal enterotoxin B (SEB) and then immunized with MBP. These mice exhibited V beta 8-specific anergy and depletion and did not develop EAE, even when further treated with SEB. However, administration of SEA to these same mice induced an initial episode of EAE which was characterized by severe hindleg paralysis and accelerated onset of disease. In contrast to SEB pretreatment, PL/J mice pretreated with SEA did develop EAE when immunized with MBP, and after resolution of clinical signs of disease these mice were susceptible to relapse of EAE induced by SEB but not by SEA. Thus, superantigens can activate encephalitogenic MBP-specific non-V beta 8+ T cells to cause EAE in PL/J mice. These data suggest that superantigens can play a central role in autoimmune disorders and that they introduce a profound complexity to autoimmune diseases such as EAE, akin to the complexity seen in multiple sclerosis.

Emergent Brazil and the Curse of the ‘Hen’s Flight’. CEPS Working Document No. 379, 27 February 2013

The ‘Emergent Brazil’ growth model is reaching its limits. Its main engines have been slowing significantly since the beginning of the global financial and economic crisis. Even its much-praised predictable macroeconomic policy has been eroded by political interference. Inflationary pressures are growing and GDP performance is anaemic. As ominous, Brazil cannot compensate for its domestic deficiencies with an export drive. Commodity exports are suffering with the world economic slow-down and the manufacturing industries’ competitiveness is in sharp decline. Brazil has put all its trade negotiation eggs into the South American and WTO baskets, and now its export market share is threatened by the Doha Round paralysis, the Latin American Alianza del Pacífico, and the US-led initiatives for a Trans-Pacific Partnership and a trade and investment agreement with the EU. Paradoxically, this alarming situation opens a window of opportunity. There is a mounting national consensus on the need to tackle head-on the country’s and its industries’ lack of competitiveness. That means finding a solution to the much-decried ‘Brazil Cost’ and stimulating private-sector investment. It also entails an aggressive trade-negotiating stance in order to secure better access to foreign markets and to foster more competition in the domestic one. The most promising near-term goal would be the conclusion of the EU–Mercosur trade talks. A scenario to overcome the paralysis of these negotiations could trail two parallel paths: bilateral EU–Brazil agreements on ‘anything but trade’ combined with a sequencing of the EU–Mercosur talks where each member of the South American bloc could adopt faster or slower liberalisation commitments and schedules.

Climate Conundrums at High Altitude. EU Diplomacy Paper 01/2014, January 2014

The European Union (EU) was the frontrunner for the establishment of the world’s first multinational emissions trading scheme (ETS). Committed to combating climate change, the EU sought to overcome the multilateral paralysis within the International Civil Aviation Organization (ICAO) to mitigate aviation emissions. Unsuccessful in pushing for a global market-based measure (MBM) within the organisation, the EU was ready for take-off to include the sector in the EU emissions trading system (EU ETS). The geographical scope, however, including all flights from and to Europe in their entire trajectory, caused frictions with the international community about sovereignty issues. Ultimately, Climate Commissioner Connie Hedegaard announced a ‘stop-the-clock’ for international flights, a temporary derogation until the 2013 ICAO Assembly in order to find a global agreement. The ’stop-the-clock’ initiative provides ample opportunity to analyse EU leadership in curbing aviation emissions based on an analytical framework specifying different types of leadership. Its shows the global challenge to the EU’s claim of structural leadership on various levels in and beyond ICAO. The paper aims to analyse to what extent the EU is a global leader in mitigating aviation emissions and to identify the kind of EU leadership according to a threefold analytical framework. In addition, it will factor in the 'stop-the-clock' initiative and to what extent it altered the perception of EU leadership in the field. The paper comes to the conclusion that EU leadership in mitigating aviation emissions is not stalling. On the contrary, the EU, by pursuing the extension of the EU ETS, has put aviation emissions on everybody’s radar – and thus showed idea-based leadership. Proving the scheme’s feasibility further underlined EU leadership, in the form of directional leadership. The 'stop-the-clock' decision, however, already indicated what was later on confirmed in the 38th ICAO Assembly: Unilateral structural leadership of the EU in the field of aviation emissions is not credible at the moment.

Do Institutional Changes Make a Difference? A veto player analysis of how institutional changes in the Council of the EU influence legislative efficiency and outputs. Brugges Political Research Paper No. 31, October 2013

A driving argument behind recent EU treaty reforms was that more qualified majority voting (QMV) was required to reduce the potential dangers of legislative paralysis caused by enlargement. Whilst existing literature on enlargement mostly focuses on the question of what changed in the legislative process after the 2004 enlargement, the question of why these changes occurred has been given far less attention. Through the use of a single veto player theoretical model, this paper seeks to test and explain whether enlargement reduces the efficiency of the legislative process and alters the type of legislation produced, and whether QMV can compensate for these effects. In doing this, it offers a theoretical explanation as to why institutional changes that alter the level of cohesion between actors in the Council have an influence over both the legislative process and its outcomes.

Transnistria – Where to? EPC Policy Brief, 13 March 2014

At the Vilnius summit of the Eastern Partnership in November 2013, Moldova initialled its Association Agreement with the EU, including a Deep and Comprehensive Free Trade Area (DCFTA) agreement, and is expected to sign the documents before the end of August 2014. Meanwhile, Russia has increased its presence and pressure in the region, as a consequence of which Armenia declined the AA and DCFTA with the EU and Ukraine, after months of protests and political paralysis, now has part of its territory occupied by Russia. Moldova is no exception to Russian pressure. As the country gets closer to upgrading relations with the EU, Russia has increased its activities in Moldova, including in the autonomous region of Gagauzia and in the breakaway region of Transnistria. Even though the “5+2” negotiations for the settlement of the Transnistria conflict continue, the number of incidents in and around this region have increased. The window of opportunity created by the involvement of Germany in the settlement of the conflict and the restart of the “5+2” negotiations in late 2011 seems to have closed. Given the recent events in the region and in Moldova/Transnistria, including the potential impact of DCFTA and visa liberalisation, Chisinau finds it increasingly difficult to manage the juggling act between its EU commitment and dialogue with Tiraspol. This Policy Brief presents the background, state of play and prospects of the Transnistria conflict while also focusing on the potential impact of Moldova’s Association Agreement with the EU on the settlement of the conflict.

Bernhardi Verzaschae Exercitatio de apoplexia et paralysi.

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