Dendritic cells rapidly undergo apoptosis in vitro following culture with activated CD4(+) V alpha 24 natural killer T cells expressing CD40L

Human V alpha 24 natural killer T (V alpha 24NKT) cells are activated by -glycosylceramide-pulsed dendritic cells (DCs) in a CDld-dependent and T-cell receptor-mediated manner. There are two major subpopulations of V alpha 24NKT cells, CD4(-) CD8(-) V alpha 24NKT and CD4(+) V alpha 24NKT cells. We have recently shown that activated CD4(-) CD8 V alpha 24NKT cells have cytotoxic activity against DCs, but knowledge of the molecules responsible for cytotoxicity of V alpha 24NKT cells is currently limited. We aimed to investigate whether CD4(+) V alpha 24NKT cells also have cytotoxic activity against DCs and to determine the mechanisms underlying any observed cytotoxic activity. We demonstrated that activated CD4(+) V alpha 24NKT cells [CD40 ligand (CD40L) -positive] have cytotoxic activity against DCs (strongly CD40-positive), but not against monocytes (weakly CD40-positive) or phytohaemagglutinin blast T cells (CD40-negative), and that apoptosis of DCs significantly contributes to the observed cytotoxicity. The apoptosis of DCs following culture with activated CD4(+) V alpha 24NKT cells, but not with resting CD4(+) V alpha 24NKT cells (CD40L-negative), was partially inhibited by anti-CD40L mAb, Direct ligation of CD40 on the DCs by the anti-CD40 antibody also induced apoptosis of DCs. Our results suggest that CD40-CD40L interaction plays an important role in the induction of apoptosis of DCs following culture with activated CD4+ Va24NKT cells. The apoptosis of DCs from normal donors. triggered by the CD40-CD40L interaction, may contribute to the homeostatic regulation of the normal human immune system, preventing the interminable activation of activated CD4(+) V alpha 24NKT cells by virtue of apoptosis of DCs.

TRAIL expression by activated human CD4(+)V alpha 24NKT cells induces in vitro and in vivo apoptosis of human acute myeloid leukema cells

Human V alpha 24NKT cells are activated by alpha -galactosylceramide (alpha -GalCer)-pulsed dendritic cells in a CD1d-dependent and a T-cell receptor-mediated manner. Here, we demonstrate that CD4(+)V alpha 24NKT cells derived from a patient with acute myeloid leukemia (AML) M4 are phenotypically similar to those of healthy donors and, in common with those derived from healthy donors, express tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) when the cells are activated by alpha -GalCer-pulsed dendritic cells but not prior to activation. We also show that myeloid that human activated CD4(+)V alpha 24NKT cells induced apoptosis of human leukemia cells in vivo. This is the first evidence that activated V alpha 24NKT cells express TRAIL and that TRAIL causes apoptosis of monocytic leukemia cells from patients with AML M4 in vitro and in vivo. Adoptive immune therapy with activated V alpha 24NKT cells, or other strategies to increase activated V alpha 24NKT cells in vivo, may be of benefit to patients with AML M4.

Functional heterogeneity within rhodamine123(lo) Hoechst33342(lo/sp) primitive hemopoietic stem cells revealed by pyronin Y

Objective. The aim of this study was to determine the function of primitive hematopoietic stem cells (PHSC) at phases G(0) and G(1) of the cell cycle. Materials and Methods. A combination of supravital dyes rhodamine123 (Rh), Hoechst33342 (Ho), and pyronin (PY) was used to isolate the G(0) and G(1) subsets of PHSC. A competitive repopulation assay was used to evaluate their in vivo function. Results. We confirmed that the Rh(lo)Lin(-)Kit(+)Sca-1(+) PHSC were relatively quiescent when compared with the more mature Rh(hi)Lin(-)Kit(+)Sca-1 HSC and Rh(hi)Lin(-)Kit(+)Sca-1(-) progenitors. In addition, cells with Rh(lo)Lin(-)Kit(+)Sca-1(+), Rh(lo)Ho(lo)Lin(-)Sca-1(+), or Rh(lo)Ho(sp)Lin(-)Sca-1(+) phenotypes identified the same cell population. We further subfractionated the Rh(lo)Ho(lo/sp)Lin(-)Sca-1(+) PHSC using PY into PYlo and PYhi subsets. Limiting dilution analysis revealed that the frequency of long-term in vivo competitive repopulating units (CRU) of the (PYRhHolo/sp)-Rh-lo-Ho-lo PHSC was 1 in 10 cells, whereas there was at least a three-fold lower frequency in those isolated at the G(1) phase (PYhi) We found a dose-dependent PY-mediated cytotoxicity that at moderate concentration affected most of the murine hematopoietic compartment but spared the early HSC compartment. Conclusion. Our data confirm that the HSC compartment is hierarchically ordered on the basis of quiescence and further extend this concept to PY-mediated cytotoxicity. PY supravital dye can be used to reveal functional heterogeneity within the (RhHolosp)-Ho-lo PHSC population but is of limited use in dissecting the relatively more mature hematopoietic stem/progenitor cell population. (C) 2001 International Society for Experimental Hematology. Published by Elsevier Science Inc.

Investigation of electrical conductivity as a function of dopant-ion radius in the systems Zr0.75Ce0.08M0.17O1.92 (M=Nd, Sm, Gd, Dy, Ho, Y, Er, Yb, Sc)

Electrical conductivity versus dopant ionic radius studies in zirconia- and ceria-based, solid oxide fuel cell (SOFC) electrolyte systems have shown that oxygen-ion conductivity is highest when the host and dopant ions are similar in size [J. Am. Ceram. Soc. 48 (1965) 286; Solid State Ionics 37 (1989) 67; Solid State Ionics 5 (1981) 547]. Under these conditions, it is thought that the conduction paths within the crystal lattice become less distorted [Solid State Ionics 8 (1983) 201]. In this study, binary ZrO2-M2O3 unit cells were expanded, via the partial substitution of Ce+4 for Zr+4 into the lattice, in an attempt to identify new, ternary, zirconia/ceria-based electrolyte systems with enhanced electrical conductivity. The compositions Zr0.75Ce0.08M0.17O1.92 (M = Nd, Sm, Gd, Dy, Ho, Y, Yb, Sc) were prepared using traditional solid state techniques. Bulk phase characterisation and precise lattice parameter measurements were performed with X-ray diffraction techniques. Four-probe DC conductivity measurements between 400 and 900 degreesC showed that the dopant-ion radius influenced electrical conductivity. The conductivity versus dopant-ion radius trends previously observed in zirconia-based, binary systems are clearly apparent in the ternary systems investigated in this study. The addition of ceria was found to have a negative influence on the electrical conductivity over the temperature range 400-900 degreesC. It is suggested that distortion of the oxygen-ion conduction path by the presence of the larger M+3 and Ce+4 species (relative to Zr+4) is the reason for the decreasing electrical conductivity as a function of increasing dopant size and ceria addition, respectively. (C) 2002 Elsevier Science B.V. All rights reserved.

A genomewide survey of developmentally relevant genes in Ciona intestinalis - V. Genes for receptor tyrosine kinase pathway and Notch signaling pathway

In the present survey, we identified most of the genes involved in the receptor tyrosine kinase (RTK), mitogen activated protein kinase (MAPK) and Notch signaling pathways in the draft genome sequence of Ciona intestinalis, a basal chordate. Compared to vertebrates, most of the genes found in the Ciona genome had fewer paralogues, although several genes including ephrin, Eph and fringe appeared to have multiplied or duplicated independently in the ascidian genome. In contrast, some genes including kit/flt, PDGF and Trk receptor tyrosine kinases were not found in the present survey, suggesting that these genes are innovations in the vertebrate lineage or lost in the ascidian lineage. The gene set identified in the present analysis provides an insight into genes for the RTK, MAPK and Notch signaling pathways in the ancient chordate genome and thereby how chordates evolved these signaling pathway.

Colet??nea de pol??ticas p??blicas: volume 2: implementaci??n de las pol??ticas y asesor??a presidencial

O principal objetivo deste livro ?? constituir uma fonte de pesquisa para o estudo do processo de produ????o e implementa????o de pol??ticas p??blicas. Por meio de textos selecionados, analisa-se o pr??prio conceito de pol??ticas p??blicas, discute-se as defini????es utilizadas para distinguir suas diversas fases e apresenta-se algumas das principais correntes te??ricas de an??lise sobre o processo de pol??ticas p??blicas.

Gobernaciones y nueva gesti??n p??blica en Venezuela

A fines de los ???80, el Estado venezolano inici?? una descentralizaci??n pol??tico-territorial produciendo cambios en las gobernaciones, instancias receptoras de competencias en este proceso, las cuales realizan reformas a trav??s de la estrategia selectiva, incorporando algunas de la propuestas de la nueva gesti??n p??blica. Este trabajo explora estas reformas. Se observan: diferencias entre los servicios sociales y los relacionados directamente con la econom??a; privatizaci??n de ??stos; traspaso a la sociedad civil de algunos servicios sociales, creaci??n de entes descentralizados; automatizaci??n de procesos; flexibilizaci??n laboral; iniciativas con lento avance en rendici??n de cuentas por resultados y capacitaci??n para una nueva cultura administrativa. En conclusi??n: la tendencia es a la conformaci??n de una gesti??n p??blica eficiente sobre la base de la reducci??n del aparato estatal, de costos sociales, as?? como de costos y conflictos laborales y escasa incorporaci??n de las propuestas de participaci??n que permiten profundizar la democracia y promover el bienestar social.

Exclusi??n social y pol??ticas de inclusi??n. Algunos elementos sobre la realidad europea y espa??ola

La globalizaci??n econ??mica ha impactado fuertemente en el mercado laboral europeo, abriendo puertas para el trabajo precario. Mientras el capital se torna global, el trabajo permanece local y m??s sumiso a los flujos econ??micos mundiales. Adem??s, los patrones de la sociedad de consumo se han consolidado, promoviendo nuevas desigualdades sociales y aumentando los riesgos de exclusi??n y vulnerabilidad social. La ca??da progresiva del industrialismo tambi??n afecta las principales bases de la estructura social como los roles de g??nero o las relaciones familiares. Diferentes redes aparecen como clave para la inclusi??n, especialmente en el actual contexto de crisis del Estado de Bienestar Social en que se encuentra Europa. Es decir, el an??lisis de la exclusi??n social debe tener en cuenta la evoluci??n de las pol??ticas sociales en toda Europa y la tendencia actual de descentralizaci??n y focalizaci??n de los ser vicios sociales. El objetivo de este art??culo es, por lo tanto, no s??lo describir el fen??meno de la exclusi??n social, sino tambi??n lanzar ideas para construir nuevos criterios de redefinici??n de las pol??ticas sociales.

Los desaf??os de las pol??ticas y la gesti??n social en Am??rica Latina

La pobreza est?? aumentando en t??rminos absolutos de manera sistem??tica desde 1990 y, desde comienzos del nuevo siglo, tambi??n en valores relativos. Hay, sin embargo, una buena nueva: el gasto p??blico social ha aumentado tambi??n de manera sistem??tica desde entonces. ??Qu?? se ha hecho con la enorme magnitud de recursos destinada a financiar las pol??ticas sociales? Hay, por un lado, limitaciones que surgen de la forma en que ellas se dise??an e implementan. La gesti??n social tradicional asume que el impacto perseguido se producir?? autom??ticamente como resultado de la mera entrega de los bienes o servicios a la poblaci??n destinataria. Aparece, adem??s, la masiva introducci??n de mecanismos de mercado en las pol??ticas sociales, bajo el supuesto que permitir??an mejorar su eficiencia e impacto. Teniendo en cuenta las limitaciones precedentes, se sugieren en este art??culo tres senderos, estos son: la superaci??n del estilo tradicional de gestionar los programas y proyectos sociales; el aprendizaje por medio de la experiencia de la evaluaci??n de impacto y del monitoreo; y la generaci??n de un estilo m??s participativo en el proceso de dise??o, gesti??n y evaluaci??n de las pol??ticas sociales.

Pol??ticas y pr??cticas para gestionar los conflictos de inter??s en Europa: una visi??n comparada

Este informe expone de forma sumaria los diversos enfoques y aproximaciones que nueve pa??ses de la Uni??n Europea ??? seis antiguos miembros (Reino Unido, Alemania, Francia, Italia, Espa??a y Portugal) y tres miembros recientes (Letonia, Polonia y Hungr??a) ??? est??n usando para gestionar los conflictos de inter??s en el sector p??blico. En la primera parte, se presenta el marco conceptual y las definiciones con las que poder entender de qu?? hablamos cuando hablamos de corrupci??n y de conflictos de inter??s en el sector p??blico. Posteriormente, trata de las razones existentes tras las pol??ticas de regulaci??n y tratamiento de los conflictos de inter??s y la importancia de ellas para el funcionamiento adecuado de la democracia. A continuaci??n, se explican las caracter??sticas, peculiaridades y dilemas de esta pol??tica p??blica en el contexto de las teor??as y enfoques sobre pol??ticas p??blicas. El informe tambi??n examina los puntos comunes en las estructuras, m??todos y procesos utilizados para gestionar los conflictos de inter??s en los pa??ses estudiados, adem??s de explicitar las principales diferencias en los marcos legales, medios de implantaci??n, mecanismos de evaluaci??n y medios de ejecuci??n. Por ??ltimo, incluye una visi??n cr??tica de las ventajas y desventajas relacionadas con la utilidad de los instrumentos empleados y finaliza con recomendaciones relativas a c??mo formular e implantar pol??ticas de este tipo.

Desenvolvimento de metodologia para determinação de Co, Cr, Fe, Mn, Ni, Se e V em amostras de água produzida da indústria do petróleo através da técnica ICP OES utilizando digestão por micro-ondas

O descarte ou reutilização da água produzida da indústria do petróleo é difícil por causa dos impactos ambientais causados devido à presença de alta salinidade e componentes tóxicos, ou pelo risco de obstrução nas colunas de produção devido à formação de incrustações que causam redução na produção de petróleo e enormes perdas no processo de extração. Assim, o conhecimento da composição química da água produzida é muito importante. O método proposto por este trabalho visa a determinação de elementos traço (Co, Cr, Fe, Mn, Ni, Se e V) em amostras de água produzida de petróleo por espectrometria de emissão óptica com plasma indutivamente acoplado (ICP OES) utilizando a digestão ácida assistida por micro-ondas para o preparo das amostras (15 g de amostra e 2 mL de HNO3 concentrado). A curva analítica construída em HNO3 2% v v-1 foi adotada para o método após verificar que não é necessário o uso de salinidade para equiparação de matriz. Para o elemento Ni, não há necessidade do uso de padrão interno, para os elementos Co, Cr, Fe, Mn e V os melhores resultados foram obtidos usando Sc como padrão interno. Para o elemento Se é recomendado o uso de Y como padrão interno. Os limites de detecção obtidos foram Co 0,67, Cr 1,2, Fe 2,3, Mn 0,49, Ni 1,9, Se 3,7 e V 5,5 μg L-1; e os limites de quantificação foram Co 2,2, Cr 4,0, Fe 7,7, Mn 1,6, Ni 6,5, Se 12,4 e V 18,3 μg L-1. A exatidão do procedimento foi verificada através de testes de recuperação em dois níveis de concentração (40 e 80 μg L-1) e análise dos materiais certificados de referência de água estuarina SLEW-2 e de água do mar NASS-5. Bons valores de recuperação foram obtidos e não houve diferença significativa (95% de confiança) entre os resultados obtidos e os valores certificados dos materiais de referência.