Subduction and collision processes in the Central Andes constrained by converted seismic phases

The Central Andes are the Earth's highest mountain belt formed by ocean-continent collision. Most of this uplift is thought to have occurred in the past 20 Myr, owing mainly to thickening of the continental crust, dominated by tectonic shortening. Here we use P-to-S (compressional-to-shear) converted teleseismic waves observed on several temporary networks in the Central Andes to image the deep structure associated with these tectonic processes. We find that the Moho (the Mohorovici? discontinuity--generally thought to separate crust from mantle) ranges from a depth of 75 km under the Altiplano plateau to 50 km beneath the 4-km-high Puna plateau. This relatively thin crust below such a high-elevation region indicates that thinning of the lithospheric mantle may have contributed to the uplift of the Puna plateau. We have also imaged the subducted crust of the Nazca oceanic plate down to 120 km depth, where it becomes invisible to converted teleseismic waves, probably owing to completion of the gabbro-eclogite transformation; this is direct evidence for the presence of kinetically delayed metamorphic reactions in subducting plates. Most of the intermediate-depth seismicity in the subducting plate stops at 120 km depth as well, suggesting a relation with this transformation. We see an intracrustal low-velocity zone, 10-20 km thick, below the entire Altiplano and Puna plateaux, which we interpret as a zone of continuing metamorphism and partial melting that decouples upper-crustal imbrication from lower-crustal thickening.     

A learning deficit related to age and beta-amyloid plaques in a mouse model of Alzheimer's disease

Mice that overexpress the human mutant amyloid precursor protein (hAPP) show learning deficits, but the apparent lack of a relationship between these deficits and the progressive beta-amyloid plaque formation that the hAPP mice display is puzzling. In the water maze, hAPP mice are impaired before and after amyloid plaque deposition. Here we show, using a new water-maze training protocol, that PDAPP mice also exhibit a separate age-related deficit in learning a series of spatial locations. This impairment correlates with beta-amyloid plaque burden and is shown in both cross-sectional and longitudinal experimental designs. Cued navigation and object-recognition memory are normal. These findings indicate that A beta overexpression and/or A beta plaques are associated with disturbed cognitive function and, importantly, suggest that some but not all forms of learning and memory are suitable behavioural assays of the progressive cognitive deficits associated with Alzheimer's-disease-type pathologies.     

Resveratrol-type oligostilbenes from Iris clarkei antagonize 20-hydroxyecdysone action in the Drosophila melanogaster B(II) cell line

Bioassay-guided high-performance liquid chromatography analysis of a MeOH extract of Iris clarkei seeds yielded the resveratrol-type oligomeric stilbenes, ampelopsin B and α-viniferin, which antagonize the action of 20-hydroxyecdysone; with a 20-hydroxyecdysone concentration of 50 nM, the ED₅₀ values were 33 μM and 10 μM, respectively. The structures of these compounds were determined by spectroscopic analysis, notably ultraviolet, liquid secondary ion mass spectrometry and modern one- and two-dimensional nuclear magnetic resonance techniques. Received 4 November 1999; accepted 13 December 1999     

MDR1, cholesterol certification and cell growth: a comparative study in normal and multidrug-resistant KB cell lines

The product of the MDR1 gene (P-gp) has been implicated in the transport of cholesterol from plasma membrane to endoplasmic reticulum for esterification. In previous studies on leukemia cell lines, we suggested that cholesterol esterification may regulate the rate of cell growth and that the MDR1 gene might be involved in this process by modulating intracellular cholesterol esters levels. To further investigate this matter, the rate of cell growth, cholesterol metabolism, expression of the MDR1 gene, and P-gp activity were compared in KB cell lines displaying differences in expression and function of P-gp (drug-sensitive phenotype versus MDR phenotype). The rate of cell growth correlated with cholesterol esterification in all KB cell lines, whereas the over-expression of MDR1 observed in the MDR cell lines was not always associated with an increased capacity of cells to esterify cholesterol. Two known inhibitors of P-gp activity, progesterone and verapamil, strongly inhibited both cholesterol esterification and cell proliferation in all KB cell lines, but they affected intracellular accumulation of labeled vinblastine only in MDR cell lines. These results further support a role for cholesterol esters in the regulation of cell growth and suggest that the P-gp expressed in MDR KB cells is not involved in the general process leading to cholesterol esterification. Received 14 February 2000; received after revision 10 April 2000; accepted 8 May 2000     

Expression and cellular distribution of perchloric acid-soluble protein is dependent on the cell-proliferating states of NRK-52E cells

To clarify the biological role of kidney perchloric acid-soluble protein 1 (K-PSP1), its expression and intracellular distribution were examined in normal rat kidney epithelial NRK-52E cells. K-PSP1 expression was low during the proliferating phase and high in the stationary phase, and shown to have a negative relationship with the protein-synthesizing activity of the cells. Immunocytochemical studies revealed that K-PSP1 is predominantly located in the cytosol, especially in endoplasmic reticulum and Golgi apparatus of proliferating cells. In the stationary phase, K-PSP1 was not detected immunologically even though protein and mRNA expression were high. This disappearance of reactivity with anti-serum seems to be due to a conformational change in K-PSP1 induced by unknown factors. These results suggest that the role of K-PSP1 is to regulate cell proliferation, and this may be related to a previously reported ability to inhibit protein synthesis.     

Avian influenza viruses infecting humans

Avian species, particularly waterfowl, are the natural hosts of influenza A viruses. Influenza viruses bearing each of the 15 hemagglutinin and nine neuraminidase subtypes infect birds and serve as a reservoir from which influenza viruses or genes are introduced into the human population. Viruses with novel hemagglutinin genes derived from avian influenza viruses, with or without other accompanying avian influenza virus genes, have the potential for pandemic spread when the human population lacks protective immunity against the new hemagglutinin. Avian influenza viruses were thought to be limited in their ability to directly infect humans until 1997, when 18 human infections with avian influenza H5N1 viruses occurred in Hong Kong. In 1999, two human infections with avian influenza H9N2 viruses were also identified in Hong Kong. These events established that avian viruses could infect humans without acquiring human influenza genes by reassortment in an intermediate host and highlighted challenges associated with the detection of human immune responses to avian influenza viruses and the development of appropriate vaccines.     

4-Hydroxynonenal-modified amyloid-beta peptide inhibits the proteasome: possible importance in Alzheimer's disease

The amyloid β-peptide (Aβ) is a 4-kDa species derived from the amyloid precursor protein, which accumulates in the brains of patients with Alzheimer’s disease. Although we lack full understanding of the etiology and pathogenesis of selective neuron death, considerable data do imply roles for both the toxic Aβ and increased oxidative stress. Another significant observation is the accumulation of abnormal, ubiquitin-conjugated proteins in affected neurons, suggesting dysfunction of the proteasome proteolytic system in these cells. Recent reports have indicated that Aβ can bind and inhibit the proteasome, the major cytoslic protease for degrading damaged and ubiquitin-conjugated proteins. Earlier results from our laboratory showed that moderately oxidized proteins are preferentially recognized and degraded by the proteasome; however, severely oxidized proteins cannot be easily degraded and, instead, inhibit the proteasome. We hypothesized that oxidatively modified Aβ might have a stronger (or weaker) inhibitory effect on the proteasome than does native Aβ. We therefore also investigated the proteasome inhibitory action of Aβ _1–40 (a peptide comprising the first 40 residues of Aβ) modified by the intracellular oxidant hydrogen peroxide, and by the lipid peroxidation product 4-hydroxynonenal (HNE). H₂O₂ modification of Aβ _1–40 generates a progressively poorer inhibitor of the purified human 20S proteasome. In contrast, HNE modification of Aβ _1–40 generates a progressively more selective and efficient inhibitor of the degradation of fluorogenic peptides and oxidized protein substrates by human 20S proteasome. This interaction may contribute to certain pathological manifestations of Alzheimer’s disease Received 26 September 2000; accepted 26 September 2000     

Estimate of human gene number provided by genome-wide analysis using Tetraodon nigroviridis DNA sequence

The number of genes in the human genome is unknown, with estimates ranging from 50,000 to 90,000 (refs 1, 2), and to more than 140,000 according to unpublished sources. We have developed 'Exofish', a procedure based on homology searches, to identify human genes quickly and reliably. This method relies on the sequence of another vertebrate, the pufferfish Tetraodon nigroviridis, to detect conserved sequences with a very low background. Similar to Fugu rubripes, a marine pufferfish proposed by Brenner et al. as a model for genomic studies, T. nigroviridis is a more practical alternative with a genome also eight times more compact than that of human. Many comparisons have been made between F. rubripes and human DNA that demonstrate the potential of comparative genomics using the pufferfish genome. Application of Exofish to the December version of the working draft sequence of the human genome and to Unigene showed that the human genome contains 28,000-34,000 genes, and that Unigene contains less than 40% of the protein-coding fraction of the human genome.