101,878 research outputs found
Medicinal chemistry of nicotinamide phosphoribosyltransferase (NAMPT) inhibitors
No full text: Nicotinamide phoshophoribosyltransferase (NAMPT) plays a key role in the replenishment of the NAD pool in cells. This in turn makes this enzyme an important player in bioenergetics and in the regulation of NAD-using enzymes, such as PARPs and sirtuins. Furthermore, there is now ample evidence that NAMPT is secreted and has a role as a cytokine. An important role of either the intracellular or extracellular form of NAMPT has been shown in cancer, inflammation, and metabolic diseases. The first NAMPT inhibitors (FK866 and CHS828) have already entered clinical trials, and a surge in interest in the synthesis of novel molecules has occurred. The present review summarizes the recent progress in this field
Aβ leads to Ca 2+ signaling alterations and transcriptional changes in glial cells
No full textThe pathogenesis of Alzheimer's disease includes accumulation of toxic amyloid beta (Aβ) peptides. A recently developed cell-permeable peptide, termed Tat-Pro, disrupts the complex between synapse-associated protein 97 (SAP97) and the α-secretase a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10), thereby leading to an alteration of the trafficking of the enzyme, which is important for nonamyloidogenic processing of amyloid precursor protein (APP). We report that Tat-Pro treatment, as well as the treatment with exogenous Aβ, deregulates Ca 2+ homeostasis specifically in astrocytes through increased expression of key components of Ca 2+ signaling, metabotropic glutamate receptor-5 and inositol 1,4,5-trisphosphate receptor-1. This is accompanied by potentiation of (S)-3,5-dihydroxyphenylglycine-induced Ca 2+ transients. Calcineurin inhibition reverts all these effects. Furthermore, our data demonstrate that astrocytes express all the components for the amyloidogenic and nonamyloidogenic processing of APP including APP itself, beta-site APP-cleaving enzyme 1 (BACE1), ADAM10, γ-secretase, and SAP97. Indeed, treatment with Tat-Pro for 48 hours significantly increased the amount of Aβ 1-42 in the medium of cultured astrocytes. Taken together, our results suggest that astroglia might be active players in Aβ production and indicate that the calcium hypothesis of Alzheimer's disease may recognize glial cells as important intermediates
WIN55212-2 attenuates amyloid-beta-induced neuroinflammation in rats through activation of cannabinoid receptors and PPAR-γ pathway
No full textCannabinoids have been shown to exert neuroprotective effects in a plethora of neurodegenerative conditions. Over the past decade, some studies demonstrate that cannabinoids can interact with nuclear peroxisome proliferator-activated receptors (PPARs). We investigated protective properties of WIN55212-2 (WIN, a non-selective cannabinoid receptor agonist) in beta-amyloid (Aβ)-induced neurodegeneration in rat hippocampus and possible involvement of PPAR-gamma (PPAR-γ). Aβ (1-42) was injected into the hippocampus of male rats. Animals were administered by intracerebroventricular rout the following treatments on days 1, 3, 5, 7: vehicle, WIN, GW9662 (selective PPAR-γ antagonist) plus WIN, AM251 (selective CB1 receptor antagonist) plus WIN, SR144528 (selective CB2 receptor antagonist) plus WIN, each of antagonists alone. Injection of Aβ-induced spatial memory impairment and a dramatic rise in hippocampal TNF-α, active caspase 3, nuclear NF-kB levels and TUNEL-positive neurons. WIN administration significantly improved memory function and diminished the elevated levels of these markers, while antagonizing either CB1 or CB2 receptor subtype partially attenuated the protective effects. Intriguingly, WIN significantly increased PPAR-γ level and transcriptional activity, the latter being partially inhibited with AM251 but not with SR144528. The enhancing effect on PPAR-γ pathway was crucial to WIN-induced neuroprotection since GW9662 partially reversed the beneficial actions of WIN. Co-administration of the three antagonists led to the complete abrogation of WIN effects. Our findings indicate that WIN exerts neuroprotective and anti-inflammatory actions against Aβ damage through both CB1 and CB2 receptors. Of great note, both direct and CB1-mediated increase in PPAR-γ signaling also contributes to WIN-induced neuroprotection
Bibliographie Hilarion G. Petzold 1958 – 2009 mit Anhang als Einführung
No full textDieses Archiv enthält die Gesamtbibliographie der Werke des Autors nebst einiger Texte „Über H. G. Petzold“ im Schlussteil der Bibliographie sowie einen Anhang mit einer Einführung in die Architektur des Werkes in seinem wissenslogischen Aufbau als Ausarbeitung seines „Tree of Science Modells“ (2007).This archive contains the complete bibliography of the author and some texts about H. G. Petzold, moreover an epilogue with an introduction to the architecture of the works in its epistemological structure and composition and as an elaborations of Petzold’s „Tree of Science Modell (2007).https://www.fpi-publikation.de/polyloge/01-2009-petzold-h-g-gesamtbibliographie-h-g-petzold-1958-2009-updating-november2009/peerReviewedpublishedVersio
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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3346: Samuel G. Freedman, author, 2013
No full textPhotograph of author Samuel G. Freedman, at NT Daily Slash meeting in the Mayborn School of Journalism at UNT
An epoxy photoresist modified by luminescent nanocrystals for the fabrication of 3D high-aspect-ratio microstructures
No full textAn epoxy-based negative-tone photoresist, which is known as a suitable material for high-aspect-ratio surface micromachining,is functionalized with red-light-emitting CdSe@ZnS nanocrystals (NCs). The proper selection of a common solvent for the NCs and the resist is found to be critical for the efficient incorporation of the NCs in the epoxy matrix. The NC-modified resist can be patterned by standard UV lithography down to micrometer-scale resolution, and high-aspect-ratio structures have been successfully fabricated on a 100 mm scaled wafer. The “as-fabricated”, 3D, epoxy-based surface microstructures show the characteristic luminescent properties of the embedded NCs, as verified by fluorescence microscopy. This issue demonstrates that the NC emission properties can be conveniently conveyed into the polymer matrix without deteriorating the lithographic performance of the latter. The dimensions, the resolution, and the surface morphology of the NC-modified-epoxy microstructures exhibit only minor deviations with respect to that of the unmodified reference material, as examined by means of microscopic and metrologic investigations. The proposed approach of the incorporation of emitting and non-bleachable NCs into a photoresist opens novel routes for surface patterning of integrated microsystems with inherent photonic functionality at the micro- and nanometer-scale for light sensing and emitting applications
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