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Stock K.,Max Delbruck Center for Molecular Medicine | Kumar J.,Max Delbruck Center for Molecular Medicine | Synowitz M.,Max Delbruck Center for Molecular Medicine | Synowitz M.,University Medicine Berlin | And 23 more authors.
Nature Medicine | Year: 2012

Primary astrocytomas of grade 3 or 4 according to the classification system of the World Health Organization (high-grade astrocytomas or HGAs) are preponderant among adults and are almost invariably fatal despite the use of multimodal therapy. Here we show that the juvenile brain has an endogenous defense mechanism against HGAs. Neural precursor cells (NPCs) migrate to HGAs, reduce glioma expansion and prolong survival time by releasing endovanilloids that activate the vanilloid receptor (transient receptor potential vanilloid subfamily member-1 or TRPV1) on HGA cells. TRPV1 is highly expressed in tumor and weakly expressed in tumor-free brain. TRPV1 stimulation triggers tumor cell death through the branch of the endoplasmic reticulum stress pathway that is controlled by activating transcription factor-3 (ATF3). The antitumorigenic response of NPCs is lost with aging. NPC-mediated tumor suppression can be mimicked in the adult brain by systemic administration of the synthetic vanilloid arvanil, suggesting that TRPV1 agonists have potential as new HGA therapeutics. © 2012 Nature America, Inc. All rights reserved.


Aretz A.,Central Facility for Electronic Microscopy | Verberckmoes S.C.,University of Antwerp | Behets G.J.,University of Antwerp | Ghadimi R.,Central Facility for Electronic Microscopy | And 6 more authors.
Journal of the American Society of Nephrology | Year: 2010

Accelerated intimal and medial calcification and sclerosis accompany the increased cardiovascular mortality of dialysis patients, but the pathomechanisms initiating microcalcifications of the media are largely unknown. In this study, we systematically investigated the ultrastructural properties of medial calcifications from patients with uremia. We collected iliac artery segments from 30 dialysis patients before kidney transplantation and studied them by radiography, microcomputed tomography, light microscopy, and transmission electron microscopy including electron energy loss spectrometry, energy dispersive spectroscopy, and electron diffraction. In addition, we performed synchrotron X-ray analyses and immunogold labeling to detect inhibitors of calcification. Von Kossa staining revealed calcification of 53% of the arteries. The diameter of these microcalcifications ranged from 20 to 500 nm, with a core-shell structure consisting of up to three layers (subshells). Many of the calcifications consisted of 2-to 10-nm nanocrystals and showed a hydroxyapatite and whitlockite crystalline structure and mineral phase. Immunogold labeling of calcification foci revealed the calcification inhibitors fetuin-A, osteopontin, and matrix gla protein. These observations suggest that uremic microcalcifications originate from nanocrystals, are chemically diverse, and intimately associate with proteinaceous inhibitors of calcification. Furthermore, considering the core-shell structure of the calcifications, apoptotic bodies or matrix vesicles may serve as a calcification nidus. Copyright © 2010 by the American Society of Nephrology.


Nick E.-M.,Institute of Ferrous Metallurgy IEHK | Muller M.G.J.,Central Facility for Electronic Microscopy | Voigt S.G.,Central Facility for Electronic Microscopy | Park D.,Central Facility for Electronic Microscopy | And 5 more authors.
Steel Research International | Year: 2012

A detailed microstructural analysis on two precipitation hardening steels of similar chemical composition and of identical heat treatment but with different microstructures and mechanical properties was performed to reveal the constituents that are of major importance for strength and toughness. Light optical microscopy, magnetic saturation measurements, energy dispersive X-ray analysis, scanning and transmission electron microscopy were used to identify and quantify the internal cleanliness, the secondary phases (δ-ferrite, retained austenite), and the copper-rich precipitates. The high purity and homogeneity of the steel's microstructure proved to be beneficial for upper shelf toughness and general isotropic behavior. In contrast, good elongation depended on local element segregation, allowing the stabilization of austenite to ambient temperature. The precipitation of copper-enriched inter-metallic phase was documented both in the martensitic matrix and in the δ-ferrite; it ensured - for given heat treatment - sufficient yield strength independent of other microstructural constituents. Due to their favorable combination of strength, toughness, and corrosion resistance precipitation hardening stainless steels are widely employed. To evaluate costs and effects of metallurgical processing and heat treatment the two steels 1.4542 and 1.4545 are compared regarding their microstructure and resulting mechanical properties. The analysis leads to a deeper understanding of how purity and microstructural constituents may impair strength, elongation, and toughness behavior. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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