Response to erythropoietin in germfree mice

Zusammenfassung Unsere gegenwärtigen Ergebnisse zeigen, dass keimfreie Mäuse dem Erythropoietin (ESF) gegenüber einen verstärkten erythrocytenerzeugenden Faktor aufweisen als normale Mäuse.     

Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse.

Amyloid-beta peptide (Abeta) seems to have a central role in the neuropathology of Alzheimer's disease (AD). Familial forms of the disease have been linked to mutations in the amyloid precursor protein (APP) and the presenilin genes. Disease-linked mutations in these genes result in increased production of the 42-amino-acid form of the peptide (Abeta42), which is the predominant form found in the amyloid plaques of Alzheimer's disease. The PDAPP transgenic mouse, which overexpresses mutant human APP (in which the amino acid at position 717 is phenylalanine instead of the normal valine), progressively develops many of the neuropathological hallmarks of Alzheimer's disease in an age- and brain-region-dependent manner. In the present study, transgenic animals were immunized with Abeta42, either before the onset of AD-type neuropathologies (at 6 weeks of age) or at an older age (11 months), when amyloid-beta deposition and several of the subsequent neuropathological changes were well established. We report that immunization of the young animals essentially prevented the development of beta-amyloid-plaque formation, neuritic dystrophy and astrogliosis. Treatment of the older animals also markedly reduced the extent and progression of these AD-like neuropathologies. Our results raise the possibility that immunization with amyloid-beta may be effective in preventing and treating Alzheimer's disease.     

Neural subsystems for object knowledge.

Critical issues in the cognitive neuroscience of language are whether there are multiple systems for the representation of meaning, perhaps organized by processing system (such as vision or language), and whether further subsystems are distinguishable within these larger ones. We describe here a patient (K.R.) with cerebral damage whose pattern of acquired deficits offers direct evidence for a major division between visually based and language-based higher-level representations, and for processing subsystems within language. K.R. could not name animals regardless of the type of presentation (auditory or visual), but had no difficulty naming other living things and objects. When asked to describe verbally the physical attributes of animals (for example, 'what colour is an elephant?'), she was strikingly impaired. Nevertheless, she could distinguish the correct physical attributes of animals when they were presented visually (she could distinguish animals that were correctly coloured from those that were not). Her knowledge of input stimulus. To explain this selective deficit, these data mandate the existence of two distinct representations of such properties in normal individuals, one visually based and one language-based. Furthermore, these data establish that knowledge of physical attributes is strictly segregated from knowledge of other properties in the language system.     

Chronic ethanol causes heterologous desensitization of receptors by reducing alpha s messenger RNA

One of the biochemical results of ethanol exposure is a change in the amount of the intracellular second messenger cyclic AMP (cAMP) produced in response to receptor stimulation. In general, acute ethanol exposure increases the amount of cAMP produced on stimulation of receptors coupled to the enzyme adenylyl cyclase via the GTP-binding protein Gs, whereas chronic ethanol exposure has the opposite effect (results for receptors coupled via Gi have been more variable). We previously reported that adaptation to continuous ethanol exposure reduces receptor-stimulated cAMP production by 25-35% in a neuroblastoma cell line (NG108-15), and an even greater reduction of 75% was observed in lymphocytes taken from actively-drinking alcoholics. This reduction in receptor-stimulated cAMP levels was recently confirmed in platelets from alcoholics. None of these studies, however, determined whether more than one receptor coupled to adenylyl cyclase activity was affected in the same cell. Here we report that chronic ethanol exposure causes desensitization of heterologous receptors coupled to Gs as cAMP production mediated by prostaglandin E1 as well as by adenosine is reduced by approximately 30% in NG108-15 cells. We show that, after chronic ethanol exposure, the activity of the alpha subunit of Gs is decreased by 29%, the amount of alpha s protein is decreased by 38.5%, and alpha s messenger RNA is decreased by 30%. Thus, cellular adaptation to ethanol involves a reduction in alpha s mRNA and, as a consequence, reduced cAMP production by heterologous receptors coupled to Gs. Such changes in cAMP production may account for the tolerance and physical dependence on ethanol in alcoholism.     

A gravitationally lensed quasar with quadruple images separated by 14.62 arcseconds

Gravitational lensing is a powerful tool for the study of the distribution of dark matter in the Universe. The cold-dark-matter model of the formation of large-scale structures (that is, clusters of galaxies and even larger assemblies) predicts the existence of quasars gravitationally lensed by concentrations of dark matter so massive that the quasar images would be split by over 7 arcsec. Numerous searches for large-separation lensed quasars have, however, been unsuccessful. All of the roughly 70 lensed quasars known, including the first lensed quasar discovered, have smaller separations that can be explained in terms of galaxy-scale concentrations of baryonic matter. Although gravitationally lensed galaxies with large separations are known, quasars are more useful cosmological probes because of the simplicity of the resulting lens systems. Here we report the discovery of a lensed quasar, SDSS J1004 + 4112, which has a maximum separation between the components of 14.62 arcsec. Such a large separation means that the lensing object must be dominated by dark matter. Our results are fully consistent with theoretical expectations based on the cold-dark-matter model.