Enhanced pathologic properties of Dutch-type mutant amyloid beta-protein.

Cerebrovascular amyloid beta-protein (Abeta) deposition is a pathological feature of several related disorders including Alzheimer disease and hereditary cerebral hemorrhage with amyloidosis Dutch-type (HCHWA-D). HCHWA-D is caused by a point mutation in the gene that encodes the Abeta precursor and results in a Glu --> Gln substitution at position 22 of Abeta. In comparison to Alzheimer disease, the cerebrovascular Abeta deposition in HCHWA-D is generally more severe, often resulting in intracerebral hemorrhage when patients reach 50 years of age. We recently reported that Abeta(1-42), but not the shorter Abeta(1-40) induces pathologic responses in cultured human leptomeningeal smooth muscle cells including cellular degeneration that is accompanied by a marked increase in the levels of cellular Abeta precursor and soluble Abeta peptide. In the present study, we show that the HCHWA-D mutation converts the normally nonpathologic Abeta(1-40) into a highly pathologic form of the peptide for cultured human leptomeningeal smooth muscle cells. These findings suggest that these altered functional properties of HCHWA-D mutated Abeta may contribute to the early and often severe cerebrovascular pathology that is the hallmark of this disorder.

(Table 1) Neodymium and Strontium measurements from sediment core MD01-2451

In the nineties, cold-water coral mounds were discovered in the Porcupine Seabight (NE Atlantic, west of Ireland). A decade later, this discovery led to the drilling of the entire Challenger cold-water coral mound (Eastern slope, Porcupine Seabight) during IODP Expedition 307. As more than 50% of the sediment within Challenger Mound consists of terrigenous material, the terrigenous component is equally important for the build-up of the mound as the framework-building corals. Moreover, the terrigenous fraction contains important information on the dynamics and the conditions of the depositional environment during mound development. In this study, the first in-depth investigation of the terrigenous sediment fraction of a cold-water coral mound is performed, combining clay mineralogy, sedimentology, petrography and Sr-Nd-isotopic analysis on a gravity core (MD01-2451G) collected at the top of Challenger Mound. Sr- and Nd-isotopic fingerprinting identifies Ireland as the main contributor of terrigenous material in Challenger Mound. Besides this, a variable input of volcanic material from the northern volcanic provinces (Iceland and/or the NW British Isles) is recognized in most of the samples. This volcanic material was most likely transported to Challenger Mound during cold climatic stages. In three samples, the isotopic ratios indicate a minor contribution of sediment deriving from the old cratons on Greenland, Scandinavia or Canada. The grain-size distributions of glacial sediments demonstrate that ice-rafted debris was deposited with little or no sorting, indicating a slow bottom-current regime. In contrast, interglacial intervals contain strongly current-sorted sediments, including reworked glacio-marine grains. The micro textures of the quartz-sand grains confirm the presence of grains transported by icebergs in interglacial intervals. These observations highlight the role of ice-rafting as an important transport mechanism of terrigenous material towards the mound during the Late Quaternary. Furthermore, elevated smectite content in the siliciclastic, glaciomarine sediment intervals is linked to the deglaciation history of the British-Irish Ice Sheet (BIIS). The increase of smectite is attributed to the initial stage of chemical weathering processes, which became activated following glacial retreat and the onset of warmer climatic conditions. During these deglaciations a significant change in the signature of the detrital fraction and a lack of coral growth is observed. Therefore, we postulate that the deglaciation of the BIIS has an important effect on mound growth. It can seriously alter the hydrography, nutrient supply and sedimentation processes, thereby affecting both sediment input and coral growth and hence, coral mound development.

Grandes escritores de America. (Siglo XIX)

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"Noticia preliminar, por R. Rojas": p.[9]-19.