Programmed cell death (apoptosis) occurs during normal development of the central nervous system. However, the mechanisms that determine which neurons will succumb to apoptosis are poorly understood. ...Blockade of N-methyl-D-aspartate (NMDA) glutamate receptors for only a few hours during late fetal or early neonatal life triggered widespread apoptotic neurodegeneration in the developing rat brain, suggesting that the excitatory neurotransmitter glutamate, acting at NMDA receptors, controls neuronal survival. These findings may have relevance to human neurodevelopmental disorders involving prenatal (drug-abusing mothers) or postnatal (pediatric anesthesia) exposure to drugs that block NMDA receptors.
Request routing in cache meshes Grimm, C; Vöckler, J.-S; Pralle, H
Computer networks and ISDN systems,
11/1998, Letnik:
30, Številka:
22
Journal Article, Conference Proceeding
Recenzirano
The current document concerns the inclusion of routing data into neighbor cache selection algorithms. The background for this work is derived from experiences in the DFN Caching Project. During this ...project, 10 cache servers were installed at the central nodes of the German Broadband Research Network (B-WiN) as an integral part of the backbone infrastructure. The fact that B-WiN contains several exchange points to other networks aggravates an intelligent and effective domain name based routing of requests within this cache hierarchy. Especially exchange points in Frankfurt and Hanover to other national networks — all containing Web servers in the same toplevel domain .de — demonstrate the insufficient possibilities in common implementations of neighbor selection algorithms. The proposed solution consists of an extended caching software to gather routing data with the help of Whois requests. These data can be evaluated in the cache selection algorithm. Starting with basic design issues, the focus of this paper is on a detailed description of an extended neighbor selection algorithm. It is concluded by the description of a full implementation in the Squid cache software.
Background: AA amyloidosis develops in patients with chronic inflammatory diseases. The AA amyloid proteins are proteolytic fragments obtained from serum amyloid A (SAA). Previous studies have ...provided evidence that endosomes or lysosomes might be involved in the processing of SAA, and contribute to the pathology of AA amyloidosis. Objective: To investigate the anatomical distribution of cathepsin (Cath) B and CathL in AA amyloidosis and their ability to process SAA and AA amyloid proteins. Methods and results: CathB and CathL were found immunohistochemically in every patient with AA amyloidosis and displayed a spatial relationship with amyloid in all the cases studied. Both degraded SAA and AA amyloid proteins in vitro. With the help of mass spectrometry 27 fragments were identified after incubation of SAA with CathB, nine of which resembled AA amyloid proteins, and seven fragments after incubation with CathL. CathL did not generate AA amyloid-like peptides. When native human AA amyloid proteins were used as a substrate 26 fragments were identified after incubation with CathB and 18 after incubation with CathL. Conclusion: The two most abundant and ubiquitously expressed lysosomal proteases can cleave SAA and AA amyloid proteins. CathB generates nine AA amyloid-like proteins by its carboxypeptidase activity, whereas CathL may prevent the formation of AA amyloid proteins by endoproteolytic activity within the N-terminal region of SAA. This is particularly interesting, because AA amyloidosis is a systemic disease affecting many organs and tissue types, almost all of which express CathB and CathL.
The majority of foodborne illnesses associated with E. coli O157 are attributed to the consumption of foods of bovine origin. In this study, RNA-Seq experiments were undertaken with E. coli O157 to ...identify genes that may be associated with growth and survival on meat and the beef carcass at low temperature. In addition, the response of an E. coli O157 isolate representative of the general genetic ‘type’ found in Australia (E. coli O157:H− strain EC2422) was compared to that of a pathogenic clinical isolate (E. coli O157:H7 strain Sakai) not typically found in Australia. Both strains up-regulated genes involved in the acid stress response, cold shock response, quorum sensing, biofilm formation and Shiga toxin production. Differences were also observed, with E. coli O157:H7 Sakai up-regulating genes playing a critical role in the barrier function of the outer membrane, lipopolysaccharide biosynthesis, extracellular polysaccharide synthesis and curli production. In contrast, E. coli O157:H− EC2422 down-regulated genes involved in peptidoglycan biosynthesis and of the primary envelope stress response Cpx system. The unique gene expression profiles of the strains, indicate that these genotypes may differ in their ability to persist in the meat production environment and therefore also in their ability to cause disease.
•E. coli O157 elicits a gene expression response that is specific to the meat matrix.•E. coli O157 exhibits a strain-specific gene expression response on meat.•E. coli O157 strains may differ in their ability to persist on meat and the carcass.
The current document summarizes the experiences obtained during the maintenance and operations of the cache hierarchy within the German broadband research network. Installed at central nodes, the ...cache service is an integral part of the backbone infrastructure. Ten distributed cache servers are the building blocks of a large scale top-level cache hierarchy. Since the beginning in January 1997, the DFN cache service was subjected to different mesh designs and conceptions. Various approaches were aimed at improvements in the load and traffic balance among the caches. At the same time, the benefit of the mesh as whole was to be increased, as well. Due to the fact that the caches are used in a production-like environment, few of the variations thought of manifested themselves in practical configurations. Maintainers of similar cache meshes may benefit from our ideas and experiences related in this document for their own conceptual design, configuration, and hardware selection. The reader might want to investigate further publications describing the design of single web caching systems
1–4.
This paper describes a novel species of ericoid mycorrhizal fungus from Australia, Cairneyella variabilis, Midgley and Tran-Dinh, gen. nov. sp. nov. The genome of C. variabilis was sequenced and a ...draft genome assembled. The draft genome of C. variabilis is 52.4 Mbp in length, and to our knowledge, this is the first study to present a genome of an ericoid mycorrhizal fungus from the southern hemisphere. Using the SignalP and dbCAN bioinformatic pipelines, a study of the catabolic potential of C. variabilis was undertaken and showed genes for an array of degradative enzymes, most of which appear to be secreted from the hyphae, to access a suite of different carbon sources. Isolates of C. variabilis have been previously shown to utilise cellulose, carboxymethyl cellulose (CMC), cellobiose, xylan, pectin, starch and tannic acid for growth, and in the current study, putative enzymes for these processes were revealed. These enzymes likely play key roles in nutrient cycling and other edaphic processes in heathland environments. ITS phylogenetic analyses showed C. variabilis to be distinct from the fungi of the “Hymenoscyphus ericae aggregate”.
Despite its global abundance, Bacillus pumilus is poorly studied. The Fairview strain was obtained from a methanogenic anaerobic coal digester. The draft genome sequence was 3.8 Mbp long and ...contained 3,890 protein-coding genes. Like the SAFR-032 strain, it includes B. pumilus-specific proteins that likely confer enhanced resistance to environmental stresses.
Interleukin-10 (IL-10) has potent anti-inflammatory and immunosuppressive properties. The potential therapeutic benefit may be compromised by the down-regulation of the non-specific immune system and ...an increased risk of infection. We studied the effects of IL-10 on important functions of native and granulocyte-macrophage colony-stimulating factor (GM-CSF) activated neutrophils and monocytes, namely phagocytosis and membrane expression of the beta superset2-integrins and of the intercellular adhesion molecule-1 (ICAM-1). In order to simulate the in vivo situation closely, we used whole blood flowcytometric assays. The effects of IL-10 (0.05, 1, 10, 100 ng/ml) were compared to those of prednisolone (10 superset-8-10 superset-5 Mol/l), an approved immunosuppressive drug which is known to impair phagocyte function. - Incubation with IL-10 for three hours significantly attenuated the ability of neutrophils to phagocytose E.coli, particularly in lower concentrations. On the other hand, high IL-10 concentrations (10, 100 ng/ml) slightly augmented monocyte phagocytosis. Similarly, expression of the beta subset2-integrins and of ICAM-1 on monocytes was markedly enhanced with IL-10 concentrations in the range from 1 to 100 ng/ml and IL-10 showed strong synergistic effects with GM-CSF in the enhancement of monocyte receptor expression. Neutrophil adhesion molecule expression was not affected. Prednisolone suppressed the phagocytosis of both cell types in a dose-dependent fashion but hardly altered the receptor numbers. Our study indicates that IL-10 can behave as a de-activator as well as an activator on the non-specific immune system, depending on the cell type and the concentration.
A lot of scientific data is not obtained from measurements but rather derived from other data by the application of computational procedures. We hypothesize that explicit representation of these ...procedures can enable documentation of data provenance, discovery of available methods, and on-demand data generation (so-called "virtual data"). To explore this idea, we have developed the Chimera virtual data system, which combines a virtual data catalog for representing data derivation procedures and derived data, with a virtual data language interpreter that translates user requests into data definition and query operations on the database. We couple the Chimera system with distributed "data grid" services to enable on-demand execution of computation schedules constructed from database queries. We have applied this system to two challenge problems, the reconstruction of simulated collision event data from a high-energy physics experiment, and searching digital sky survey data for galactic clusters, with promising results.
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