Deficiency of MALT1 paracaspase activity results in unbalanced regulatory and effector T and B cell responses leading to multiorgan inflammation

The paracaspase MALT1 plays an important role in immune receptor-driven signaling pathways leading to NF-κB activation. MALT1 promotes signaling by acting as a scaffold, recruiting downstream signaling proteins, as well as by proteolytic cleavage of multiple substrates. However, the relative contributions of these two different activities to T and B cell function are not well understood. To investigate how MALT1 proteolytic activity contributes to overall immune cell regulation, we generated MALT1 protease-deficient mice (Malt1(PD/PD)) and compared their phenotype with that of MALT1 knockout animals (Malt1(-/-)). Malt1(PD/PD) mice displayed defects in multiple cell types including marginal zone B cells, B1 B cells, IL-10-producing B cells, regulatory T cells, and mature T and B cells. In general, immune defects were more pronounced in Malt1(-/-) animals. Both mouse lines showed abrogated B cell responses upon immunization with T-dependent and T-independent Ags. In vitro, inactivation of MALT1 protease activity caused reduced stimulation-induced T cell proliferation, impaired IL-2 and TNF-α production, as well as defective Th17 differentiation. Consequently, Malt1(PD/PD) mice were protected in a Th17-dependent experimental autoimmune encephalomyelitis model. Surprisingly, Malt1(PD/PD) animals developed a multiorgan inflammatory pathology, characterized by Th1 and Th2/0 responses and enhanced IgG1 and IgE levels, which was delayed by wild-type regulatory T cell reconstitution. We therefore propose that the pathology characterizing Malt1(PD/PD) animals arises from an immune imbalance featuring pathogenic Th1- and Th2/0-skewed effector responses and reduced immunosuppressive compartments. These data uncover a previously unappreciated key function of MALT1 protease activity in immune homeostasis and underline its relevance in human health and disease.

Catalpa speciosa (Warder)

Von v. St. Paul, Corvetten-Capitain z. D. und Hofmarschall weiland Sr. Königlichen Hoheit des Prinzen Adalbert von Preussen

Swahili-Sprachführer

von Walter von St. Paul-Illaire

La asthéneia en la antropología cristiana primitiva

La Patrística cristiana recibió la noción veterotestamentaria de asthéneia de la versión griega de los LXX. Entendida como “debilidad" y “falta de fuerza", se la asoció con “enfermedad" o “estado general de debilidad", significado que se conservó tanto en los libros históricos como en los poéticos. El término aparece con frecuencia también en los Evangelios y en los escritos de Pablo, posibilitando así una comprensión de la enfermedad en clave filosófico-teológica por parte de los Padres, entre los que se destaca el Patriarca de Constantinopla San Juan Crisóstomo, quien recurriendo a una exégesis literal de la Escritura según los principios de la escuela antioquena, analiza el concepto en sus comentarios a las Epístolas llamadas “Mayores" de San Pablo y, particularmente, a la Segunda Carta a los Corintios. De esta lectura se desprende la necesidad de considerar la asthéneia de manera inseparable de la antropología cristiana. En los orígenes del cristianismo la concepción de hombre resultaba extremadamente compleja, oscilando desde la antropología tripartita de San Pablo (I Tes. 5, 23) a la quíntuple presentada por ciertos textos gnósticos (Carta esotérica de Santiago 11, 36-12, 17; 14, 24-36) y a la década de Clemente de Alejandría (Strómata VI, 16, 135, 1-2). El estudio de la aplicación del concepto de asthéneia a los distintos componentes del hombre en la polifacética literatura cristiana primitiva, permite comprender la importancia asignada a cada uno de ellos según las distintas corrientes interpretativas.

Isotope geochemistry of Ninetyeast Ridge basalts

The Ninetyeast Ridge lavas have Sr and Nd isotopic ratios intermediate between those of Indian Ocean MORBs and those of the very enriched Kerguelen hot spot. In an Nd-Sr isotope diagram, they also plot close to the fields of St. Paul Island lavas and of the early magmatism on Kerguelen Archipelago. The Ninetyeast Ridge lavas were generated by mixing among at least three components: a depleted, MORB-type component, such as the one erupted today on the Southeast Indian Ridge; a very enriched, high- Sr/ Sr, low-epsilon-Nd, OIB-type component (the Kerguelen hot spot); and an OIB-type component comparable to that sampled from the St. Paul (and Amsterdam) lavas. The Ninetyeast Ridge lavas show a typical Dupal anomaly signature and Pb, Sr, and Nd isotopic systematics indicate that the Kerguelen hot spot was involved in the ridge's formation as the Indian plate moved northward. The different sites cored during ODP Leg 121 show a trend in their isotopic compositions, from less radiogenic Pb/ Pb ratios and intermediate 87Sr/86Sr and 143Nd/**Nd ratios in the oldest lavas (Site 758) toward more radiogenic 206Pb/204Pb, higher epsilon-Nd, and lower 87Sr/86Sr values in the youngest lavas (Site 756). The lavas from Site 757 have 206Pb/204Pb ratios intermediate between those of the lavas from Sites 756 and 758 and higher 87Sr/86Sr and lower epsilon-Nd values. The relative proportions of the hot spot(s) and MORB component have evolved with time, reflecting differences of tectonic setting: the relative proportion of the Kerguelen hot spot component appears lower in the younger Site 756 lavas than in the older lavas from Sites 757 and 758. Site 756 coincides with the beginning of rifting at the Southeast Indian Ridge, about 43 Ma ago. The formation of the early Kerguelen Archipelago lavas may have drained most of the plume-derived material toward the Antarctic plate. Alternatively, the proximity of the spreading-ridge axis may account for the isotopic similarity of the Site 756 lavas to young lavas erupted on the Southeast Indian Ridge, from 33? to 37?S. The older lavas of Ninetyeast Ridge may have formed when the hot spot and ridge axis did not exactly coincide. The involvement of the third component, a St. Paul hot spot, in the genesis of the Ninetyeast Ridge lavas, especially for the Site 756 lavas, is clearly indicated by Sr, Pb, and Nd isotope systematics and also by trace element ratios. These data, together with those from the Kerguelen Plateau, indicate that the Kerguelen hot spot has been active more or less continuously in the South Indian Ocean for at least 115 Ma. This could indicate that the plume, and by inference the Dupal anomaly, is deep seated in origin.

Mineralogy and geochemistry of a basalt from ODP Hole 119-738C

The Lower Cretaceous tholeiitic basalt cored at Site 738, on the southernmost part of the Kerguelen Plateau, shows anomalous Sr, Nd, and Pb isotopic compositions compared to other lavas from Kerguelen Island and the Kerguelen Plateau. The strongly negative value of eNd (- 8.5) and high 207Pb/204Pb ratio (15.71) reflect a long-term evolution in a source high in Nd/Sm and µ. These geochemical properties, not observed in the Indian Ocean mantle plumes (St. Paul, Kerguelen Islands), have been reported for alkali lavas erupted in East Antarctica, thus suggesting that they originate from the Gondwana subcontinental lithosphere.

London, England, 1742 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: London surveyed, or, a new map of the cities of London and Westminster and the borough of Southwark : shewing the several streets and lanes with the most of the alleys & thorough fairs with the additional new buildings to this present year 1742. It was printed for John Bowles at the Black Horse in Cornhill in 1742. Scale [ca. 1:5,280]. The image inside the map neatline is georeferenced to the surface of the earth and fit to the British National Grid coordinate system (British National Grid, Airy Spheroid OSGB (1936) Datum). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, drainage, selected buildings (some shown pictorially), built-up areas, docks, city district boundaries, and more. Relief is shown pictorially. Includes illustrations, tables of fares, and views: South prospect of London -- North prospect of St. Paul's Cathedral -- Bank of England -- Front of the Royal Exchange -- Banqueting House -- Treasury. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

London, England, 1830 (Image 6 of 6) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Map of London : made from an actual survey in the years 1824, 1825, & 1826, by C. & J. Greenwood, extended and comprising the various improvements to 1830 ; engraved by Josiah Neele. It was published by C. & J. Greenwood August 31st, 1830. Scale [ca. 1: 63,360]. This layer is image 6 of 6 total images of the six sheet source map, representing the southeast portion of the map. The image inside the map neatline is georeferenced to the surface of the earth and fit to the British National Grid coordinate system (British National Grid, Airy Spheroid OSGB (1936) Datum). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, drainage, selected buildings, industry locations (e.g. mills, factories, etc.), docks, parks, cemeteries, ground cover, windmills, city district boundaries, and more. Relief is shown by hachures. Includes view of St. Paul's Cathedral, "Explanation" table for points of interest & "References to the Parishes &c." This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

Influência da clorexidina na adesão ao esmalte

Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz

Avaliação in vitro da microinfiltração marginal de resinas de polimerização aumentada pela técnica directa

Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz

Avaliação in vitro da resistência adesiva à microtracção e caracterização morfológica com SEM de um novo sistema adesivo

Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz

Nd and Sr isotope record of ODP Sites 121-756 and 122-762 sediments

We have analyzed the Nd isotopic composition of both ancient seawater and detrital material from long sequences of carbonated oozes of the South Indian Ocean which are ODP Site 756 (Ninety East Ridge (-30°S), 1518 m water depth) and ODP Site 762 (Northwest Australian margin, 1360 m water depth). The measurements indicate that the epsilon-Nd changes in Indian seawater over the last 35 Ma result from changes in the oceanic circulation, large volcanic and continental weathering Nd inputs. This highlights the diverse nature of those controls and their interconnections in a small area of the ocean. These new records combined with those previously obtained at the equatorial ODP Sites 757 and 707 in the Indian Ocean (Gourlan et al., 2008, doi:10.1016/j.epsl.2007.11.054) established that the distribution of intermediate seawater epsilon-Nd was uniform over most of the Indian Ocean from 35 Ma to 10 Ma within a geographical area extending from 40°S to the equator and from -60°E to 120°E. However, the epsilon-Nd value of Indian Ocean seawater which kept an almost constant value (at about -7 to -8) from 35 to 15 Ma rose by 3 epsilon-Nd units from 15 to 10 Ma. This sharp increase has been caused by a radiogenic Nd enrichment of the water mass originating from the Pacific flowing through the Indonesian Passage. Using a two end-members model we calculated that the Nd transported to the Indian Ocean through the Indonesian Pathway was 1.7 times larger at 10 Ma than at 15 Ma. The Nd isotopic composition of ancient seawater and that of the sediment detrital component appear to be strongly correlated for some specific events. A first evidence occurs between 20 and 15 Ma with two positive spikes recorded in both epsilon-Nd signals that are clearly induced by a volcanic crisis of, most likely, the St. Paul hot-spot. A second evidence is the very large epsilon-Nd decrease recorded at ODP Sites 756 and 762 during the past 10 Ma which has never been previously observed. The synchronism between the epsilon-Nd decrease in seawater from 10 to 5 Ma and evidences of desertification in the western part of the nearly Australian continent suggests enhanced weathering inputs in this ocean from this continent as a result of climatic changes.

The works of Matthew Arnold.

"This edition consists of seven hundred and seventy-five copies."

The southern reporter.

Vols. 6-142: Permanent ed.

Cases and readings on law and society,

Bibliographical footnotes.