Mouse CD11c(+) B220(+) Gr1(+) plasmacytoid dendritic cells develop independently of the T-cell lineage.

The developmental origin of dendritic cells (DCs) is controversial. In the mouse CD8alpha(+) and CD8alpha(-) DC subsets are often considered to be of lymphoid and myeloid origin respectively, although evidence on this point is conflicting. Very recently a novel CD11c(+) B220(+) DC subset has been identified that appears to be the murine counterpart to interferon alpha (IFNalpha)-producing human plasmacytoid DCs (PDCs). We show here that CD11c(+) B220(+) mouse PDCs, like human PDCs, are present in the thymus and express T lineage markers such as CD8alpha and CD4. However, the intrathymic development of PDCs can be completely dissociated from immature T lineage cells in mixed chimeras established with bone marrow cells from mice deficient for either Notch-1 or T-cell factor 1, two independent mutations that severely block early T-cell development. Our data indicate that thymic PDCs do not arise from a bipotential T/DC precursor.

DL4-mediated Notch signaling is required for the development of fetal αβ and γδ T cells.

T-cell development depends upon interactions between thymocytes and thymic epithelial cells (TECs). The engagement of delta-like 4 (DL4) on TECs by Notch1 expressed by blood-borne BM-derived precursors is essential for T-cell commitment in the adult thymus. In contrast to the adult, the earliest T-cell progenitors in the embryo originate in the fetal liver and migrate to the nonvascularized fetal thymus via chemokine signals. Within the fetal thymus, some T-cell precursors undergo programmed TCRγ and TCRδ rearrangement and selection, giving rise to unique γδ T cells. Despite these fundamental differences between fetal and adult T-cell lymphopoiesis, we show here that DL4-mediated Notch signaling is essential for the development of both αβ and γδ T-cell lineages in the embryo. Deletion of the DL4 gene in fetal TECs results in an early block in αβ T-cell development and a dramatic reduction of all γδ T-cell subsets in the fetal thymus. In contrast to the adult, no dramatic deviation of T-cell precursors to alternative fates was observed in the fetal thymus in the absence of Notch signaling. Taken together, our data reveal a common requirement for DL4-mediated Notch signaling in fetal and adult thymopoiesis.

Beyond the enlargement

Con la Europa del 2004 acercándose rápidamente, esta obra no pretende re-explorar el proceso de ampliación una vez más. Este trabajo pretende aportar una perspectiva aproximativa de aquello que le espera a la Unión Europea tras su ampliación. El acento se pone en las distintas oportunidades y desafíos que la acción exterior de la Unión tendrá que afrontar en su futuro ampliado, centrándose especialmente en la UE-25 como una actor en política exterior a la vez que un proveedor de seguridad. El objetivo de los capítulos de la primera parte de este volumen es reflejar cómo se producirá la adaptación de los nuevos miembros a las cuatro áreas de impacto exterior de la UE (PESC, PESD, minorías y asilo), y consecuentemente, de qué modo influirán éstos nuevos actores. En la última parte de la obra, se explora la naturaleza de las nuevas fronteras de la UE-25.

A critical lineage-nonspecific role for pTalpha in mediating allelic and isotypic exclusion in TCRbeta-transgenic mice.

Although it is well established that early expression of TCRbeta transgenes in the thymus leads to efficient inhibition of both endogenous TCRbeta and TCRgamma rearrangement (also known as allelic and "isotypic" exclusion, respectively) the role of pTalpha in these processes remains controversial. Here, we have systematically re-evaluated this issue using three independent strains of TCRbeta-transgenic mice that differ widely in transgene expression levels, and a sensitive intracellular staining assay that detects endogenous TCRVbeta expression in individual immature thymocytes. In the absence of pTalpha, both allelic and isotypic exclusion were reversed in all three TCRbeta-transgenic strains, clearly demonstrating a general requirement for pre-TCR signaling in the inhibition of endogenous TCRbeta and TCRgamma rearrangement. Both allelic and isotypic exclusion were pTalpha dose dependent when transgenic TCRbeta levels were subphysiological. Moreover, pTalpha-dependent allelic and isotypic exclusion occurred in both alphabeta and gammadelta T cell lineages, indicating that pre-TCR signaling can potentially be functional in gammadelta precursors. Finally, levels of endogenous RAG1 and RAG2 were not down-regulated in TCRbeta-transgenic immature thymocytes undergoing allelic or isotypic exclusion. Collectively, our data reveal a critical but lineage-nonspecific role for pTalpha in mediating both allelic and isotypic exclusion in TCRbeta-transgenic mice.

Servidor municipal de datos espaciales con capacidad para WMTS : aplicación al callejero municipal de Malgrat de Mar

El sistema inclou un servidor d'aplicacions, un servidor de dades espacials i un sistema gestor de bases de dades alfanumèriques; dóna servei de mapes sota l'especificació Web Map Tile Service, de l'OGC, i s'explica el procés de confecció dels tiles per a cada nivell de zoom amb el programari GeoWebCache integrat en Geoserver. Mostra l'estructura de matrius de tessel·les (TileMatrix) i piràmides (TileMatrixSets). Implementa un portal visualitzador de mapes (geoportal), capaç per a WMTS i WMS, amb les opcions d'exploració de capes i consulta a la base de dades del carrerer oficial de l'Ajuntament de Malgrat de Mar

Dynamic regulation of notch 1 and notch 2 surface expression during T cell development and activation revealed by novel monoclonal antibodies.

It is well established that Notch signaling plays a critical role at multiple stages of T cell development and activation. However, detailed analysis of the cellular and molecular events associated with Notch signaling in T cells is hampered by the lack of reagents that can unambiguously measure cell surface Notch receptor expression. Using novel rat mAbs directed against the extracellular domains of Notch1 and Notch2, we find that Notch1 is already highly expressed on common lymphoid precursors in the bone marrow and remains at high levels during intrathymic maturation of CD4(-)CD8(-) thymocytes. Notch1 is progressively down-regulated at the CD4(+)CD8(+) and mature CD4(+) or CD8(+) thymic stages and is expressed at low levels on peripheral T cells. Immunofluorescence staining of thymus cryosections further revealed a localization of Notch1(+)CD25(-) cells adjacent to the thymus capsule. Notch1 was up-regulated on peripheral T cells following activation in vitro with anti-CD3 mAbs or infection in vivo with lymphocytic chorio-meningitis virus or Leishmania major. In contrast to Notch1, Notch2 was expressed at intermediate levels on common lymphoid precursors and CD117(+) early intrathymic subsets, but disappeared completely at subsequent stages of T cell development. However, transient up-regulation of Notch2 was also observed on peripheral T cells following anti-CD3 stimulation. Collectively our novel mAbs reveal a dynamic regulation of Notch1 and Notch2 surface expression during T cell development and activation. Furthermore they provide an important resource for future analysis of Notch receptors in various tissues including the hematopoietic system.

Notch1 deficiency dissociates the intrathymic development of dendritic cells and T cells.

Thymic dendritic cells (DCs) form a discrete subset of bone marrow (BM)-derived cells, the function of which is to mediate negative selection of autoreactive thymocytes. The developmental origin of thymic DCs remains controversial. Although cell transfer studies support a model in which T cells and thymic DCs develop from the same intrathymic pluripotential precursor, it remains possible that these two types of cells develop from independent intrathymic precursors. Notch proteins are cell surface receptors involved in the regulation of cell fate specification. We have recently reported that T cell development in inducible Notch1-deficient mice is severely impaired at an early stage, before the expression of T cell lineage markers. To investigate whether development of thymic DCs also depends on Notch1, we have constructed mixed BM chimeric mice. We report here that thymic DC development from Notch1(-/)- BM precursors is absolutely normal (in terms of absolute number and phenotype) in this competitive situation, despite the absence of Notch1(-/)- T cells. Furthermore, we find that peripheral DCs and Langerhans cells are also not affected by Notch1 deficiency. Our results demonstrate that the development of DCs is totally independent of Notch1 function, and strongly suggest a dissociation between intrathymic T cell and DC precursors.

Revisão das espécies de Ceroplastinae Atkinson (Hemiptera, Coccoidea, Coccidae) do Estado de São Paulo, Brasil

As espécies de Ceroplastinae (Hemiptera, Coccoidea, Coccidae) que ocorrem no Estado de São Paulo são revisadas. São estudadas 36 espécies de Ceroplastinae, das quais 9 são sinonimizadas, 8 espécies novas são descritas e 19 são redescritas. Ceroplastes campinensis Hempel, 1901, C. bicolor Hempel, 1901, C. excaericae Hempel, 1912 e C. farmairii (Signoret, 1866), mencionadas para o Estado de São Paulo, não foram examinadas, devido a não localização do material tipo ou de outros exemplares. Nossos estudos indicaram que C. albolineatus Cockerell, 1894 e C. confluens Cockerell & Tinsley, 1898 foram erroneamente citadas por Hempel, 1900 para o estado de São Paulo. Coccus stellifer Westwood, 1871, atualmente Vinsonia stellifera (Westwood, 1871), é transferida para gênero Ceroplastes como Ceroplastes stellifer (Westwood, 1871) n. comb. C. flosculoides Matile-Ferrero, 1993 é registrada pela primeira vez para o país e C. cassiae (Chavannes, 1848), C. deodorensis Hempel, 1937, C. formosus Hempel, 1900 e C. quadratus Green, 1935 são registradas pela primeira vez no Estado de São Paulo. Ceroplastinae é agora representada por 31 espécies no Estado de São Paulo, todas incluídas no gênero Ceroplastes. Ilustrações e uma chave para espécies são incluídas. Novos sinônimos: C. formicarius Hempel = Ceroplastes communis Hempel, 1900 n. sin.; C. janeirensis Gray, 1828 = Ceroplastes psidii (Chavannes, 1848) n. sin. = C. simplex Hempel, 1900 n. sin.; C. cirripediformis Comstock, 1881 = C. cultus Hempel, 1900 n. sin. = C. cuneatus Hempel, 1900 n. sin. = C. rarus Hempel, 1900 n. sin e C. rotundus Hempel, 1900 n. sin.; C. lucidus Hempel, 1900 = C. novaesi Hempel, 1900 n. sin.; C. grandis Hempel, 1900 = C. rhizophorae Hempel, 1918 n. sin. Novas espécies descritas: C. acutus sp. nov.; C. bragai sp. nov.; C. coronatus sp. nov; C. glomeratus sp. nov; C. jordanensis sp. nov.; C. minimus sp. nov.; C. solanaceus sp. nov.; C. willinkae sp. nov. Espécies redescritas: C. agrestis Hempel, 1932; C. cassiae (Chavannes, 1848); C. cirripediformis; C. deodorensis Hempel, 1900; C. diospyros Hempel, 1928; C. floridensis Comstock, 1881; C. flosculoides Matile-Ferrero, 1993; C. formicarius Hempel, 1900; C. formosus Hempel, 1900; C. grandis Hempel, 1900; C. gregarius Hempel, 1932; C. iheringi Cockerell, 1895; C. janeirensis; C. lucidus; C. purpureus Hempel, 1900; C. quadratus Green, 1935; C. speciosus Hempel, 1900; C. stellifer e C. variegatus Hempel, 1900. São designados lectótipos e paralectótipos para C. agrestis, C. deodorensis, C. diospyros, C. formosus, C. purpureus, C. speciosus e C. variegatus e um neótipo para C. cassiae.

Expression and presentation of endogenous mouse mammary tumor virus superantigens by thymic and splenic dendritic cells and B cells.

Tolerance against superantigens (SAgs) encoded by endogenous mouse mammary tumor virus (Mtv) loci involves the intrathymic deletion of SAg-reactive T cells expressing a particular TCR V beta-chain, presumably upon presentation of the SAg by specialized APC. However, although the role of dendritic cells (DC) in the induction of tolerance against conventional Ags has been demonstrated, little is known about the role played by DC in tolerance induction against Mtv SAgs. Moreover, there is conflicting evidence concerning the capacity of DC to express and present Mtv SAgs. In this report we have analyzed the expression of Mtv SAgs in highly purified thymic and splenic DC and B cells by reverse transcriptase-PCR, using primers amplifying Mtv SAg-specific spliced mRNAs. DC express Mtv SAgs at levels comparable to B cells, but display a differential expression pattern of the various Mtv loci compared with B cells. Furthermore, our results show that DC are able to induce the deletion of SAg-reactive thymocytes in an in vitro assay, indicating that Mtv SAgs are functionally expressed on the DC surface. Collectively, our data are consistent with the hypothesis that DC play a role in the induction of intrathymic tolerance to Mtv SAgs.

TCRgamma silencing during alphabeta T cell development depends upon pre-TCR-induced proliferation.

During thymus development, immature T cells become committed to two distinct lineages based upon expression of alphabeta or gammadelta TCR. In the alphabeta lineage, developing thymocytes progressively extinguish transcription of the TCRgamma genes by a poorly understood process known as gamma silencing. We show that alphabeta lineage thymocytes in mice lacking a functional pre-TCR undergo limited proliferation and fail to silence TCRgamma genes during development. Stimulation of pre-TCR-deficient immature thymocytes with anti-CD3 Abs does not directly down-regulate TCRgamma transcription but restores TCRgamma silencing following proliferation. Collectively our data reveal an important role for pre-TCR induced proliferation in activating the TCRgamma silencer in alphabeta lineage thymocytes, a process that may reinforce alphabeta or gammadelta lineage commitment.

Cutting edge: thymic crosstalk regulates delta-like 4 expression on cortical epithelial cells.

Interactions between Notch1 receptors on lymphoid progenitors and Delta-like 4 (DL4) ligands on cortical thymic epithelial cells (cTEC) are essential for T cell lineage commitment, expansion, and maturation in the thymus. Using a novel mAb against DL4, we show that DL4 levels on cTEC are very high in the fetal and neonatal thymus when thymocyte expansion is maximal but decrease dramatically in the adult when steady-state homeostasis is attained. Analysis of mutant mouse strains where thymocyte development is blocked at different stages indicates that lymphostromal interactions ("thymus crosstalk") are required for DL4 down-regulation on cTEC. Reconstitution of thymocyte development in these mutant mice further suggests that maturation of thymocytes to the CD4(+)CD8(+) stage and concomitant expansion are needed to promote DL4 down-regulation on cTEC. Collectively, our data support a model where thymic crosstalk quantitatively regulates the rate of Notch1-dependent thymopoiesis by controlling DL4 expression levels on cTEC.

Mental disorders in offspring of parents with bipolar and major depressive disorders.

OBJECTIVES: There is limited information on the specificity of associations between parental bipolar disorder (BPD) and major depressive disorder (MDD) and the risk of psychopathology in offspring. The chief aim of the present study was to investigate the association between mood disorder subtypes in the two parents and mental disorders in the offspring. METHODS: A total of 376 offspring (aged 6.0-17.9 years; mean=11.5years) of 72 patients with BPD (139 offspring), 56 patients with MDD (110 offspring), and 66 controls (127 offspring) participated in a family study conducted in two university hospital centers in Switzerland. Probands, offspring, and biological co-parents were interviewed by psychologists blind to proband diagnoses, using a semi-structured diagnostic interview. RESULTS: Rates of mood and anxiety disorders were elevated among offspring of BPD probands (34.5% any mood; 42.5% any anxiety) and MDD probands (25.5% any mood; 44.6% any anxiety) as compared to those of controls (12.6% any mood; 22.8% any anxiety). Moreover, recurrent MDD was more frequent among offspring of BPD probands (7.9%) than those of controls (1.6%). Parental concordance for bipolar spectrum disorders was associated with a further elevation in the rates of mood disorders in offspring (64.3% both parents versus 27.2% one parent). CONCLUSIONS:   These findings provide unique information on the broad manifestations of parental mood disorders in their offspring. The earlier onset and increased risk of recurrent MDD in the offspring of parents with BPD compared to those of controls suggests that the episodicity characterizing BPD may emerge in childhood and adolescence.