54 research outputs found

    The Role of Attractin in Neurodegeneration Caused by Oxidative Stress

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    Oxidative stress is linked to dopaminergic (DA) neurodegeneration in Parkinson’s disease. Our laboratory reported slowly progressive DA neurodegeneration in the zitter (zi) rat, which is Attractin (Atrn) deficient. However, little is known about the function of Atrn in the central nervous system (CNS). Thus, we investigated whether DA neurodegeneration in the zi rat was induced by oxidative stress, and how Atrn affects oxidative stress. First, we summarize our previous in vivo data, which revealed suppression of DA neurodegeneration using antioxidants (vitamin E and melatonin) in zi rats. Second, our current ex vivo and in vitro studies are introduced. Using primary neuronal cultures of zi mesencephalon as a model of Atrn-deficient neurons or Atrn-GFP-overexpressing HEK293 cells, accumulation of reactive oxygen species (ROS) in mitochondria and cell viability was examined under oxidative stress. Atrn-deficient neurons accumulated excess ROS in mitochondria, resulting in neurodegeneration, whereas Atrn-overexpressing cells showed suppression of ROS accumulation under oxidative stress. These results showed that Atrn plays a suppressive role against ROS and that the loss of Atrn function induced excess ROS accumulation and led to DA neurodegeneration. This is the first report to show that Atrn directly modulates mitochondrial ROS accumulation in the CNS

    Intrinsic Promoter Activities of Primary DNA Sequences in the Human Genome

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    In order to understand an overview of promoter activities intrinsic to primary DNA sequences in the human genome within a particular cell type, we carried out systematic quantitative luciferase assays of DNA fragments corresponding to putative promoters for 472 human genes which are expressed in HEK (human embryonic kidney epithelial) 293 cells. We observed the promoter activities of them were distributed in a bimodal manner; putative promoters belonging to the first group (with strong promoter activities) were designated as P1 and the latter (with weak promoter activities) as P2. The frequencies of the TATA-boxes, the CpG islands, and the overall G + C-contents were significantly different between these two populations, indicating there are two separate groups of promoters. Interestingly, similar analysis using 251 randomly isolated genomic DNA fragments showed that P2-type promoter occasionally occurs within the human genome. Furthermore, 35 DNA fragments corresponding to putative promoters of non-protein-coding transcripts (ncRNAs) shared similar features with the P2 in both promoter activities and sequence compositions. At least, a part of ncRNAs, which have been massively identified by full-length cDNA projects with no functional relevance inferred, may have originated from those sporadic promoter activities of primary DNA sequences inherent to the human genome

    Impurity emission characteristics of long pulse discharges in Large Helical Device

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    Line spectra from intrinsic impurity ions have been monitored during the three kinds of long-pulse discharges (ICH, ECH, NBI). Constant emission from the iron impurity shows no preferential accumulation of iron ion during the long-pulse operations. Stable Doppler ion temperature has been also measured from Fe XX, C V and C III spectra

    Following the Birth of a Nanoplasma Produced by an Ultrashort Hard-X-Ray Laser in Xenon Clusters

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    X-ray free-electron lasers (XFELs) made available a new regime of x-ray intensities, revolutionizing the ultrafast structure determination and laying the foundations of the novel field of nonlinear x-ray optics. Although earlier studies revealed nanoplasma formation when an XFEL pulse interacts with any nanometer-scale matter, the formation process itself has never been decrypted and its timescale was unknown. Here we show that time-resolved ion yield measurements combined with a near-infrared laser probe reveal a surprisingly ultrafast population (similar to 12 fs), followed by a slower depopulation (similar to 250 fs) of highly excited states of atomic fragments generated in the process of XFEL-induced nanoplasma formation. Inelastic scattering of Auger electrons and interatomic Coulombic decay are suggested as the mechanisms populating and depopulating, respectively, these excited states. The observed response occurs within the typical x-ray pulse durations and affects x-ray scattering, thus providing key information on the foundations of x-ray imaging with XFELs

    Real-time observation of X-ray-induced intramolecular and interatomic electronic decay in CH2I2

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    The increasing availability of X-ray free-electron lasers (XFELs) has catalyzed the development of single-object structural determination and of structural dynamics tracking in realtime. Disentangling the molecular-level reactions triggered by the interaction with an XFEL pulse is a fundamental step towards developing such applications. Here we report real-time observations of XFEL-induced electronic decay via short-lived transient electronic states in the diiodomethane molecule, using a femtosecond near-infrared probe laser. We determine the lifetimes of the transient states populated during the XFEL-induced Auger cascades and find that multiply charged iodine ions are issued from short-lived (similar to 20 fs) transient states, whereas the singly charged ones originate from significantly longer-lived states (similar to 100 fs). We identify the mechanisms behind these different time scales: contrary to the short-lived transient states which relax by molecular Auger decay, the long-lived ones decay by an interatomic Coulombic decay between two iodine atoms, during the molecular fragmentation
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