On the correctness and efficiency of independent and-parallelism in logic programs

This paper presents and proves some fundamental results for independent and-parallelism (IAP). First, the paper treats the issues of correctness and efficiency: after defining strict and non-strict goal independence, it is proved that if strictly independent goals are executed in parallel the solutions obtained are the same as those produced by standard sequential execution. It is also shown that, in the absence of failure, the parallel proof procedure doesn't genérate any additional work (with respect to standard SLDresolution) while the actual execution time is reduced. The same results hold even if non-strictly independent goals are executed in parallel, provided a trivial rewriting of such goals is performed. In addition, and most importantly, treats the issue of compile-time generation of IAP by proposing conditions, to be written at compile-time, to efficiently check strict and non-strict goal independence at run-time and proving the sufficiency of such conditions. It is also shown how simpler conditions can be constructed if some information regarding the binding context of the goals to be executed in parallel is available to the compiler trough either local or program-level analysis. These results therefore provide a formal basis for the automatic compile-time generation of IAP. As a corollary of such results, the paper also proves that negative goals are always non-strictly independent, and that goals which share a first occurrence of an existential variable are never independent.

A simulation study on parallel backtracking with solution memoing for independent and-parallelism

Goal-level Independent and-parallelism (IAP) is exploited by scheduling for simultaneous execution two or more goals which will not interfere with each other at run time. This can be done safely even if such goals can produce multiple answers. The most successful IAP implementations to date have used recomputation of answers and sequentially ordered backtracking. While in principle simplifying the implementation, recomputation can be very inefficient if the granularity of the parallel goals is large enough and they produce several answers, while sequentially ordered backtracking limits parallelism. And, despite the expected simplification, the implementation of the classic schemes has proved to involve complex engineering, with the consequent difficulty for system maintenance and expansion, and still frequently run into the well-known trapped goal and garbage slot problems. This work presents ideas about an alternative parallel backtracking model for IAP and a simulation studio. The model features parallel out-of-order backtracking and relies on answer memoization to reuse and combine answers. Whenever a parallel goal backtracks, its siblings also perform backtracking, but after storing the bindings generated by previous answers. The bindings are then reinstalled when combining answers. In order not to unnecessarily penalize forward execution, non-speculative and-parallel goals which have not been executed yet take precedence over sibling goals which could be backtracked over. Using a simulator, we show that this approach can bring significant performance advantages over classical approaches.

Automatic unrestricted independent and-parallelism in logic programs

We present new algorithms which perform automatic parallelization via source-to-source transformations. The objective is to exploit goal-level, unrestricted independent andparallelism. The proposed algorithms use as targets new parallel execution primitives which are simpler and more flexible than the well-known &/2 parallel operator, which makes it possible to generate better parallel expressions by exposing more potential parallelism among the literals of a clause than is possible with &/2. The main differences between the algorithms stem from whether the order of the solutions obtained is preserved or not, and on the use of determinacy information. We briefly describe the environment where the algorithms have been implemented and the runtime platform in which the parallelized programs are executed. We also report on an evaluation of an implementation of our approach. We compare the performance obtained to that of previous annotation algorithms and show that relevant improvements can be obtained.

A segment-swapping approach for executing trapped computations

We consider the problem of supporting goal-level, independent andparallelism (IAP) in the presence of non-determinism. IAP is exploited when two or more goals which will not interfere at run time are scheduled for simultaneous execution. Backtracking over non-deterministic parallel goals runs into the wellknown trapped goal and garbage slot problems. The proposed solutions for these problems generally require complex low-level machinery which makes systems difficult to maintain and extend, and in some cases can even affect sequential execution performance. In this paper we propose a novel solution to the problem of trapped nondeterministic goals and garbage slots which is based on a single stack reordering operation and offers several advantages over previous proposals. While the implementation of this operation itself is not simple, in return it does not impose constraints on the scheduler. As a result, the scheduler and the rest of the run-time machinery can safely ignore the trapped goal and garbage slot problems and their implementation is greatly simplified. Also, standard sequential execution remains unaffected. In addition to describing the solution we report on an implementation and provide performance results. We also suggest other possible applications of the proposed approach beyond parallel execution.

Participación directa de los trabajadores en la Siderúrgica del Orinoco 'Alfredo Maneiro', Venezuela

Esta investigación, en progreso, se propone caracterizar la participación de los trabajadores promovida en la industria siderúrgica de la región Guayana, Venezuela. Los referentes que sustentan esta investigación se orientan a las categorías de participación de los trabajadores en la toma de decisiones en empresas bajo dos vertientes principales en estudio: la democracia industrial y la gestión o dirección participativa. La investigación se desarrolla bajo una estrategia de acompañamiento a los trabajadores de las mesas de trabajo, en el marco de la Investigación Acción Participativa (IAP), en particular la Sistematización de Experiencias. La ejecución de talleres de formación – investigación con la estrategia de grupos focales facilitó el intercambio de información. El período considerado, para esta fase, se refiere a los encuentros e intercambios entre octubre 2011 y marzo 2012. Los resultados de la sistematización de experiencias de participación en la Siderúrgica del Orinoco (SIDOR) se enmarcan en dimensiones asociadas al origen de la participación, las formas de participación y niveles alcanzados, distinguiendo la participación directa de la indirecta. Los productos de la sistematización comprenden el diseño del taller sobre Participación Directa, un documento síntesis y una presentación para comunicar la experiencia.

Estrategias para la participación de los trabajadores en mejoras tecnológicas asociadas a la industria metalúrgica venezolana

Se planteó la generación y sistematización de estrategias para la participación de los trabajadores en mejoras tecnológicas asociadas a la industria metalúrgica venezolana. Se desarrolló una estrategia de acompañamiento desde la investigación acción participativa (IAP), la ‘investigación próxima’, mediante talleres de formación-investigación y la sistematización de experiencias considerando la perspectiva y necesidades de los actores. Bajo este enfoque, se ejecutaron 10 talleres (de tres tipos), con una participación promedio de 15 trabajadores por taller, en las empresas metalúrgicas de hierro-acero y aluminio de la región Guayana, Venezuela. Desde estos talleres, en un contexto de diálogo de saberes, se validó la propuesta de ‘formación-investigación’ como estrategia útil de intervención en espacios liderados por los trabajadores, a partir de los que surgieron nuevas herramientas prácticas (‘mi historia con la tecnología’, ‘bitácora de aprendizaje’) para la sistematización de su propia experiencia. Estos resultados dan cuenta de la posibilidad de integración de los intereses de los involucrados (trabajadores e investigadores), enriqueciendo el enfoque y el método, mediante las estrategias de encuentro, de sistematización de los propios métodos y de conformación de los ‘colectivos de saberes’, considerando la ‘deriva de la investigación’, bajo discursos prácticos-teóricos propios, como posibilidad de posicionamiento de su participación en los asuntos tecnológicos de sus respectivas organizaciones.

Participación Directa y Aprendizaje de los Trabajadores en Mejoras Tecnológicas a Empresas Bajo Gestión Colectiva. Aplicación en Industrias Metalúrgicas de Venezuela y Argentina

La industria metalúrgica estatal venezolana ha vivido, desde sus inicios, procesos cíclicos de cambios y ajustes tecnológicos. Estos procesos no han sido objeto de sistematización que asegure el aprendizaje y apropiación del conocimiento. Este hecho, aún hoy, ha obstaculizado los procesos de apropiación y mejora de las tecnologías asociadas al sector. A partir del acompañamiento a iniciativas de participación de grupos de interés surgidos del seno de los trabajadores, se planteó esta investigación que tuvo como propósito la determinación de condiciones y relaciones para su participación directa en los procesos de mejora de las tecnologías existentes y el fortalecimiento del aprendizaje asociado. Se consideraron dos ámbitos Latinoamericanos donde hay manifestación de gestión colectiva y participación: Venezuela y Argentina. En el caso venezolano, el abordaje se realizó bajo la Investigación Acción Participativa (IAP), desarrollando la “investigación próxima”, como estrategia de acompañamiento, mediante “talleres de formación-investigación” y la sistematización de experiencias considerando la perspectiva y necesidades de los actores. En el caso argentino, el abordaje se realizó mediante visitas, entrevistas, reuniones y encuentros. Los talleres realizados en Venezuela, en un contexto de diálogo de saberes, facilitaron el surgimiento de herramientas prácticas para la sistematización de su propia experiencia (“Preguntas generadoras”, “Mi historia con la tecnología”, “Bitácora de aprendizaje”). El intercambio con los pares argentinos ha generado una red que plantea la posibilidad de construcción y nucleación conjunta de saberes y experiencia, tanto para los trabajadores como para los investigadores. Los casos estudiados referidos a las empresas recuperadas por los trabajadores (ERTs) argentinos evidencian un proceso de participación marcada por su autonomía en la gestión de la empresa, dadas las circunstancias que los llevó a asumirla para conservar sus puestos de trabajo. De estos casos emergieron categorías asociadas con elementos de gestión de un proceso técnico–tecnológico, como la participación en la planificación, concepción o diseño de la mejora. La participación en general está asociada al hecho asambleario, vinculado a las prácticas de toma de decisiones autogestionarias como expresión de una alta participación. La Asamblea, como máxima instancia de participación, y el Consejo de Administración son las formas de participación prevalecientes. En cuanto al aprendizaje, los trabajadores de las ERTs argentinas aportaron categorías de gran significación a los procesos de socialización del conocimiento: conocimiento colectivo y cooperación del conocimiento, rescate de los saberes y formación de trabajadores que tomen el relevo. Las categorías surgidas de las ERTs argentinas, los referentes teóricos y el interés de los trabajadores venezolanos fueron la base para la valoración tanto de su grado de participación en las mejoras a procesos tecnológicos emprendidas, como del aprendizaje asociado. Ésta valoración se realizó bajo una aproximación borrosa dado el carácter ambiguo de estas categorías que fueron trabajadas como conjuntos que se relacionan, más que como variables. Se encontró que la participación, se configura como un sub-conjunto del aprendizaje para contribuir a su fortalecimiento. Las condiciones y relaciones para fortalecer la participación en los asuntos tecnológicos surgieron a partir de la sistematización y síntesis de ambas experiencias (Venezuela y Argentina) conjugando una estructura que contempla la formación para la nucleación de colectivos de saberes (proyectos de mejora o innovaciones), las redes por afinidad, la sistematización de su propia experiencia técnica y los enlaces institucionales. Estos resultados dan cuenta de la integración de los intereses de las partes (trabajadores, investigadores, instituciones), mediante las estrategias de encuentro, de sistematización de los propios métodos y de conformación de los “colectivos de saberes”, la red de IAP en la industria (IAP Industrial) considerando la “deriva de la investigación”, bajo discursos práctico–teóricos propios, como posibilidad de posicionamiento de su participación en los asuntos tecnológicos de sus respectivas organizaciones, abriendo una oportunidad de ampliación de la experiencia en otros ámbitos y sectores. ABSTRACT Venezuelan's state owned steel industry has experienced since its earliest years, cycles of change and technological adjustments. These processes have not been systematized to ensure learning and knowledge in those organizations. This fact, even today, has hindered the processes of appropriation and improving the technologies associated with the sector. In order to support initiatives involving metalworker interest groups, this research was aimed at determining conditions and relations for their direct participation in process improvements to existing technologies and strengthening the associated learning. Two Latin American countries, Venezuela and Argentina, were considered on the base of their collective management and participation experiences. The Venezuelan approach was carried out under the Participatory Action Research (PAR) strategy, through the ‘proximal research’ as support strategy, by means of ‘workshops–research’ and systematization of experiences considering the perspective and needs of actors. Workshops were carried out in metallurgical enterprises from steel and aluminum at Guayana, Venezuela and its affiliates in the Central region. Those industries have been promoted collective management. The Argentine approach was carried out through visits, interviews, meetings and gatherings. The workshops held in Venezuela, in a dialogue of knowledge context, facilitated the emergence of tools for the systematization of their own experience (‘generating questions’, ‘My history with technology’, ‘Learning Log’). The relation with Argentine peers has generated a network that creates opportunities of knowledge and experience construction and its nucleation for both, workers and researchers. The cases studied relating to Argentine workers’ recuperated enterprises show a participatory process marked by autonomy in the management of the factory, given the circumstances that led them to take it in order to maintain their jobs. From these cases emerged categories associated with management aspects about technical-technology process, such as participation in planning, design or implementation of the improvement. Participation, in general, is associated with assemblies, joined to the practices of self-management decision-making as an expression of a high participation. The Cooperative General Assembly, as the highest instance of participation, and the Board of Directors are the prevalent forms of participation. In relation to learning, Argentine workers’ recuperated enterprises provided categories of great significance to the process of socialization of knowledge: collective knowledge and knowledge cooperation, recovery of knowledge and training workers for replacement. Based on categories arising from the Argentine experience, theoretical framework and the interest of the Venezuelan workers the assessment of both, their degree of participation on technical improvements and the associated technological learning were made considering a fuzzy approach, given the ambiguous nature of these categories that were worked as sets rather than variables. It was found that participation is configured as a subset of learning to contribute to its strengthening. The conditions and relations to strengthen participation in technology issues emerged from the systematization and synthesis of both experiences (Venezuela and Argentina) combining a structure which provides training for the nucleation of collectives of knowledge (improvement projects or innovations), affinity networks, systematization of their own expertise and institutional links. These results show the integration of the interests of stakeholders (workers, researchers, institutions) through strategies like meetings, systematization of their own methods, forming ‘collectives of technological knowledge’ and a participative action research network in this industry (Industrial PAR) considering the ‘research drift’, under their own practical-theoretical discourses positioned as a possibility of their participation in technological activities in their respective organizations, opening an opportunity for scaling to other areas and sectors.

Estudio para un Modelo de Gestión de un Acuífero Costero, mediante Metodologías Participativas y Análisis Geoestadístico en el marco del Desarrollo Local. Manglaralto, Ecuador

El presente estudio se fundamenta en la investigación-acción-participativa (IAP), para buscar alternativas que tiendan al desarrollo local de un territorio. Se centra en la cuenca hidrográfica del rio Manglaralto-Santa Elena-Ecuador, aplicando un sistema metodológico participativo que considera las características peculiares del territorio, que se analizan geoespacialmente reconociendo la influencia de la dinámica de sus cambios y observando los móviles que la propiciaban. A través de mecanismos participativos, se conectan los aspectos técnicos para el conocimiento y el aprovechamiento racional del acuífero costero, con los valores de los habitantes del territorio, para mejorar su abastecimiento de agua y crear nuevas condiciones y oportunidades en el camino del desarrollo local, vislumbrando la sostenibilidad. Cabe indicar que el ente administrativo y propulsor es la Junta de Agua Potable Regional Manglaralto (JAPRM). La hipótesis del estudio considera, que los métodos participativos generan en la comunidad una respuesta basada en su identidad y sus deseos de mejorar, que propiciará una gestión del acuífero costero que conlleve al desarrollo local. Otra hipótesis complementaria estipula que las estrategias del gobierno respecto al turismo propicia un crecimiento en la demanda del agua del acuífero. En Manglaralto-Ecuador, una parroquia de 30.000 habitantes aproximadamente, donde la JAPRM, administra y suministra agua a 23.586 habitantes que cuenta en su organización, llevada por 6 representantes de las comunidades rurales que la conforman, empezaron hace 7 años a buscar una forma de lograr un cambio, de tener agua para el desarrollo de la comunidad. Buscaron ayuda por diferentes medios, políticos, económicas, sociales y encontraron como base fundamental a la cooperación con el Organismo Internacional de Energía Atómica (OIEA) y la Escuela Superior Politécnica del Litoral (ESPOL) para entrelazar aspectos técnicos, ambientales, sociales y culturales. La gestión del acuífero costero, desde la perspectiva del IAP repercute en el desarrollo de Manglaralto. También se realiza un análisis geoespacial-geoestadístico, para vislumbrar aspectos de cambios en el territorio ligados al crecimiento turístico, que afectan a la demanda del recurso agua proveniente del acuífero costero bajo la administración de la JAPRM. La tesis presenta el modelo integral y propio de la comunidad de Manglaralto, que refleja una evolución que alcanzó un apogeo en 2011 y parte del 2012, con 9 pozos de agua que daban servicio los 365 días del año, 24 horas al día ininterrumpidamente. Las condiciones externas (promociones turísticas de la ruta del Spondylus) han repercutido en nuevas problemáticas (crecimiento elevado de la demanda del agua). El acuífero costero se convierte en el emblema y móvil de solución, gracias a la gestión integral y a la interacción IAP que se amolda a la evolución de las condiciones, buscando soluciones para la comunidad y su entorno. El modelo integral del territorio con la participación de sus pobladores, considera el aspecto turístico, como un agente que propicia la mayor demanda del agua. Situación a la que hay que dar respuesta mediante la observación-reflexión en el ciclo del IAP para generar nuevas directrices estratégicas y gestionar el desarrollo local. ABSTRACT The present study is based on the participatory action research (PAR) methodology in order to look for alternatives which tend to the local development of a territory. It focuses on the Manglaralto hydrographic river basin located in Santa Elena-Ecuador through the application of the participatory methodology which considers the peculiar characteristics of the territory. These are geospatially analyzed recognizing the influence of its dynamic of changes and observing the causes that originated them. Through the use of participatory mechanisms, technical aspects are connected for stimulating knowledge and rational use of the coastal aquifer with the values of inhabitants of the territory to improve the water supply and create new conditions of sustainability. It is important to point out that the administrative organism and promoter is the Manglaralto Regional Fresh Water Board (JAPRM). In Manglaralto-Ecuador, a parish of approximately 30,000 inhabitants, the MRFWB manages and supplies water to 23.586 inhabitants. This organization is composed by 6 representatives of rural communities. It started 7 years ago looking for a way to achieve a change, from obtaining water to developing the community. They seeked for help in different fields such as: political, economic and social and they found International Atomic Energy Agency (IAEA) and Escuela Superior Politécnica del Litoral (ESPOL) as a fundamental basis for cooperation to bond technical, environmental, social and cultural aspects. Management of coastal aquifer, from the PAR perspective affects the development of Manglaralto. Also, a geospatial and geostatistical analysis is carried out to distinguish change aspects in territories related to touristy growth which affects the demand of water obtained from the coastal aquifer under the management of the MRFWB. The thesis presents a comprehensive model that belongs to the Manglaralto community and reveals an evolution that reached a peak in 2011 and part of 2012, with 9 water wells that operated the 365 days of the year 24 hours a day without interruption. The external conditions (touristic packages of Spondylus route) have created new problems (higher demand of water). The coastal aquifer is a symbol and solution, thanks to the comprehensive management and PAR interaction which fits the evolution of conditions, looking for solutions for the community and its surroundings. The comprehensive model of territory with the participation of inhabitants considers the touristic aspect as an agent which brings about a higher demand of water. This situation requests a response through the observation-reflection in the PAR cycle to generate new strategic guidelines and promote the local development.

Suppression of tumor necrosis factor-induced cell death by inhibitor of apoptosis c-IAP2 is under NF-κB control

Members of the NF-κB/Rel and inhibitor of apoptosis (IAP) protein families have been implicated in signal transduction programs that prevent cell death elicited by the cytokine tumor necrosis factor α (TNF). Although NF-κB appears to stimulate the expression of specific protective genes, neither the identities of these genes nor the precise role of IAP proteins in this anti-apoptotic process are known. We demonstrate here that NF-κB is required for TNF-mediated induction of the gene encoding human c-IAP2. When overexpressed in mammalian cells, c-IAP2 activates NF-κB and suppresses TNF cytotoxicity. Both of these c-IAP2 activities are blocked in vivo by coexpressing a dominant form of IκB that is resistant to TNF-induced degradation. In contrast to wild-type c-IAP2, a mutant lacking the C-terminal RING domain inhibits NF-κB induction by TNF and enhances TNF killing. These findings suggest that c-IAP2 is critically involved in TNF signaling and exerts positive feedback control on NF-κB via an IκB targeting mechanism. Functional coupling of NF-κB and c-IAP2 during the TNF response may provide a signal amplification loop that promotes cell survival rather than death.

Inhibition of Reaper-induced apoptosis by interaction with inhibitor of apoptosis proteins (IAPs)

IAPs comprise a family of inhibitors of apoptosis found in viruses and animals. In vivo binding studies demonstrated that both baculovirus and Drosophila IAPs physically interact with an apoptosis-inducing protein of Drosophila, Reaper (RPR), through their baculovirus IAP repeat (BIR) region. Expression of IAPs blocked RPR-induced apoptosis and resulted in the accumulation of RPR in punctate perinuclear locations which coincided with IAP localization. When expressed alone, RPR rapidly disappeared from the cells undergoing RPR-induced apoptosis. Expression of P35, a caspase inhibitor, also blocked RPR-induced apoptosis and delayed RPR decline, but RPR remained cytoplasmic in its location. Mutational analysis of RPR demonstrated that caspases were not directly responsible for RPR disappearance. The physical interaction of IAPs with RPR provides a molecular mechanism for IAP inhibition of RPR’s apoptotic activity.

Evolutionary conservation of apoptosis mechanisms: Lepidopteran and baculoviral inhibitor of apoptosis proteins are inhibitors of mammalian caspase-9

We cloned a new inhibitor of apoptosis protein (IAP) homolog, SfIAP, from Spodoptera frugiperda Sf-21 cells, a host of insect baculoviruses. SfIAP contains two baculovirus IAP repeat domains followed by a RING domain. SfIAP has striking amino acid sequence similarity with baculoviral IAPs, CpIAP and OpIAP, suggesting that baculoviral IAPs may be host-derived genes. SfIAP and baculoviral CpIAP inhibit Bax but not Fas-induced apoptosis in human cells. Their apoptosis-suppressing activity in mammalian cells requires both baculovirus IAP repeat and RING domains. Further biochemical data suggest that SfIAP and CpIAP are specific inhibitors of mammalian caspase-9, the pinnacle caspase in the mitochondria/cytochrome c pathway for apoptosis, but are not inhibitors of downstream caspase-3 and caspase-7. Thus the mechanisms by which insect and baculoviral IAPs suppress apoptosis may involve inhibition of an insect caspase-9 homologue. Peptides representing the IAP-binding domain of the Drosophila cell death protein Grim abrogated human caspase suppression by SfIAP and CpIAP, implying evolutionary conservation of the functions of IAPs and their inhibitors.

A transient outward-rectifying K+ channel current down-regulated by cytosolic Ca2+ in Arabidopsis thaliana guard cells

Sustained (noninactivating) outward-rectifying K+ channel currents have been identified in a variety of plant cell types and species. Here, in Arabidopsis thaliana guard cells, in addition to these sustained K+ currents, an inactivating outward-rectifying K+ current was characterized (plant A-type current: IAP). IAP activated rapidly with a time constant of 165 ms and inactivated slowly with a time constant of 7.2 sec at +40 mV. IAP was enhanced by increasing the duration (from 0 to 20 sec) and degree (from +20 to −100 mV) of prepulse hyperpolarization. Ionic substitution and relaxation (tail) current recordings showed that outward IAP was mainly carried by K+ ions. In contrast to the sustained outward-rectifying K+ currents, cytosolic alkaline pH was found to inhibit IAP and extracellular K+ was required for IAP activity. Furthermore, increasing cytosolic free Ca2+ in the physiological range strongly inhibited IAP activity with a half inhibitory concentration of ≈ 94 nM. We present a detailed characterization of an inactivating K+ current in a higher plant cell. Regulation of IAP by diverse factors including membrane potential, cytosolic Ca2+ and pH, and extracellular K+ and Ca2+ implies that the inactivating IAP described here may have important functions during transient depolarizations found in guard cells, and in integrated signal transduction processes during stomatal movements.

Baculovirus inhibitors of apoptosis (IAPs) block activation of Sf-caspase-1

We have investigated the ability of Sf-caspase-1 and two mammalian caspases, caspase-1 and caspase-3, to induce apoptosis in Spodoptera frugiperda Sf-21 insect cells. While the transient expression of the pro-Sf-caspase-1 did not induce apoptosis, expression of the pro-domain deleted form, p31, or coexpression of the two subunits of mature Sf-caspase-1, p19 and p12, induced apoptosis in Sf-21 cells. The behavior of Sf-caspase-1 resembled that of the closely related mammalian caspase, caspase-3, and contrasted with that of the mammalian caspase-1, the pro-form of which was active in inducing apoptosis in Sf-21 cells. The baculovirus caspase inhibitor P35 blocked apoptosis induced by active forms of all three caspases. In contrast, members of the baculovirus inhibitor of apoptosis (IAP) family failed to block active caspase-induced apoptosis. However, during viral infection, expression of OpIAP or CpIAP blocked the activation of pro-Sf-caspase-1 and the associated induction of apoptosis. Thus, the mechanism by which baculovirus IAPs inhibit apoptosis is distinct from the mechanism by which P35 blocks apoptosis and involves inhibition of the activation of pro-caspases like Sf-caspase-1.

Thymocyte-targeted overexpression of xiap transgene disrupts T lymphoid apoptosis and maturation

The X-linked inhibitor of apoptosis (XIAP) and other members of the inhibitor of apoptosis (IAP) family can suppress apoptosis induced by a diverse variety of triggers. Functional studies done to date have focused on tissue culture models and adenovirus overexpression of XIAP and other IAP proteins. Here we report the phenotype of an engineered transgenic mouse overexpressing a human IAP, as well as assessing the long-term consequence of IAP overexpression. We document the relative protein expression levels of the endogenous mouse homologue to XIAP, mouse inhibitor of apoptosis (MIAP 3), within thymocyte and T cell subpopulations. The consequence of lymphoid-targeted overexpression of XIAP in transgenic mice suggests a physiological role for the endogenous protein, MIAP3. Xiap-transgenic mice accumulated thymocytes and/or T cells in primary and secondary lymphoid tissue, T cell maturation was perturbed, and transgenic thymocytes resisted a variety of apoptotic triggers both in vitro and in vivo. These observations imply a possible key function for the intrinsic cellular inhibitor XIAP in maintaining the homeostasis of the immune system.

Abrogation of disease development in plants expressing animal antiapoptotic genes

An emerging topic in plant biology is whether plants display analogous elements of mammalian programmed cell death during development and defense against pathogen attack. In many plant–pathogen interactions, plant cell death occurs in both susceptible and resistant host responses. For example, specific recognition responses in plants trigger formation of the hypersensitive response and activation of host defense mechanisms, resulting in restriction of pathogen growth and disease development. Several studies indicate that cell death during hypersensitive response involves activation of a plant-encoded pathway for cell death. Many susceptible interactions also result in host cell death, although it is not clear how or if the host participates in this response. We have generated transgenic tobacco plants to express animal genes that negatively regulate apoptosis. Plants expressing human Bcl-2 and Bcl-xl, nematode CED-9, or baculovirus Op-IAP transgenes conferred heritable resistance to several necrotrophic fungal pathogens, suggesting that disease development required host–cell death pathways. In addition, the transgenic tobacco plants displayed resistance to a necrogenic virus. Transgenic tobacco harboring Bcl-xl with a loss-of-function mutation did not protect against pathogen challenge. We also show that discrete DNA fragmentation (laddering) occurred in susceptible tobacco during fungal infection, but does not occur in transgenic-resistant plants. Our data indicate that in compatible plant–pathogen interactions apoptosis-like programmed cell death occurs. Further, these animal antiapoptotic genes function in plants and should be useful to delineate resistance pathways. These genes also have the potential to generate effective disease resistance in economically important crops.