244 research outputs found

    Cryptotomography: reconstructing 3D Fourier intensities from randomly oriented single-shot diffraction patterns

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    We reconstructed the 3D Fourier intensity distribution of mono-disperse prolate nano-particles using single-shot 2D coherent diffraction patterns collected at DESY's FLASH facility when a bright, coherent, ultrafast X-ray pulse intercepted individual particles of random, unmeasured orientations. This first experimental demonstration of cryptotomography extended the Expansion-Maximization-Compression (EMC) framework to accommodate unmeasured fluctuations in photon fluence and loss of data due to saturation or background scatter. This work is an important step towards realizing single-shot diffraction imaging of single biomolecules.Comment: 4 pages, 4 figure

    NQO2 is a reactive oxygen species generating off-target for acetaminophen

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    [Image: see text] The analgesic and antipyretic compound acetaminophen (paracetamol) is one of the most used drugs worldwide. Acetaminophen overdose is also the most common cause for acute liver toxicity. Here we show that acetaminophen and many structurally related compounds bind quinone reductase 2 (NQO2) in vitro and in live cells, establishing NQO2 as a novel off-target. NQO2 modulates the levels of acetaminophen derived reactive oxygen species, more specifically superoxide anions, in cultured cells. In humans, NQO2 is highly expressed in liver and kidney, the main sites of acetaminophen toxicity. We suggest that NQO2 mediated superoxide production may function as a novel mechanism augmenting acetaminophen toxicity

    Identification of Impact Craters in Foils from the Stardust Interstellar Dust Collector

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    The Stardust Interstellar Dust Collection tray provides the first opportunity for the direct laboratory-based measurement of contemporary interstellar dust. The total exposed surface of the tray was approximately 0.1 square meters, including 153 square centimeters of Al foil in addition to the silica aerogel tiles that are the primary collection medium. Preliminary examination of aerogel tiles has already revealed 16 tracks from particle impacts with an orientation consistent with an interstellar origin, and to date four of the particles associated with these tracks have a composition consistent with an extraterrestrial origin. Tentative identification of impact craters on three foil samples was also reported previously. Here we present the definitive identification of 20 impact craters on five foils

    Role of TRAIL and the pro-apoptotic Bcl-2 homolog Bim in acetaminophen-induced liver damage

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    Acetaminophen (N-acetyl-para-aminophenol (APAP), paracetamol) is a commonly used analgesic and antipyretic agent. Although considered safe at therapeutic doses, accidental or intentional overdose causes acute liver failure characterized by centrilobular hepatic necrosis with high morbidity and mortality. Although many molecular aspects of APAP-induced cell death have been described, no conclusive mechanism has been proposed. We recently identified TNF-related apoptosis-inducing ligand (TRAIL) and c-Jun kinase (JNK)-dependent activation of the pro-apoptotic Bcl-2 homolog Bim as an important apoptosis amplification pathway in hepatocytes. In this study, we, thus, investigated the role of TRAIL, c-JNK and Bim in APAP-induced liver damage. Our results demonstrate that TRAIL strongly synergizes with APAP in inducing cell death in hepatocyte-like cells lines and primary hepatocyte. Furthermore, we found that APAP strongly induces the expression of Bim in a c-JNK-dependent manner. Consequently, TRAIL- or Bim-deficient mice were substantially protected from APAP-induced liver damage. This study identifies the TRAIL-JNK-Bim axis as a novel target in the treatment of APAP-induced liver damage and substantiates its general role in hepatocyte death
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