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| 553. |
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| 554. |
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| 555. |
- Szekely, L, et al.
(author)
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Human herpesvirus-8-encoded LNA-1 accumulates in heterochromatin- associated nuclear bodies
- 1999
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In: The Journal of general virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 8080 ( Pt 11), s. 2889-2900
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Journal article (peer-reviewed)abstract
- Subnuclear distribution of the human herpesvirus-8 (HHV-8)- encoded nuclear protein LNA-1 was analysed at high resolution in body cavity (BC) lymphoma-derived cell lines, in cell hybrids between BC cells and various human and mouse cells and in freshly infected K562 and ECV cell lines. Three-dimensional reconstruction of nuclei from optical sections and quantitative analysis of the distribution of LNA-1 fluorescence in relation to chromatin showed that LNA-1 associates preferentially with the border of heterochromatin in the interphase nuclei. This was further confirmed in the following systems: in endo- and exonuclease-digested nuclei, in human–mouse (BC-1–Sp2- 0) hybrids and on chromatin spreads. LNA-1 was found to bind to mitotic chromosomes at random. Epstein–Barr virus (EBV), but not HHV-8, was rapidly lost from mouse–human hybrid cells in parallel with the loss of human chromosomes. HHV-8 could persist on the residual mouse background for more than 8 months. In early human–mouse hybrids that contain a single fused nucleus, LNA-1 preferentially associates with human chromatin. After the gradual loss of the human chromosomes, LNA-1 becomes associated with the murine pericentromeric heterochromatin. In human–human hybrids derived from the fusion of the HHV-8-carrying BCBL-1 cells and the EBV-immortalized lymphoblastoid cell line IB4, LNA-1 did not co-localize with EBNA-1, EBNA-2, EBNA-5 or EBNA-6. LNA-1 was not associated with PML containing ND10 bodies either. DNase but not RNase or detergent treatment of isolated nuclei destroys LNA-1 bodies. In advanced apoptotic cells LNA- 1 bodies remain intact but are not included in the apoptotic bodies themselves.
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| 556. |
- Tanaka, T., et al.
(author)
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Data acquisition system for the PoGOLite astronomical hard X-ray polarimeter
- 2007
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In: Nuclear Science Symposium Conference Record, 2007. - 9781424409228 ; , s. 445-449, s. 445-449
-
Conference paper (other academic/artistic)abstract
- The PoGOLite is a new balloon-borne instrument to measure the polarization of hard X-rays/soft gamma-rays in the 25-80 keV energy range for the first time. In order to detect the polarization, PoGOLite measures the azimuthal angle asymmetry of Compton scattering and the subsequent photo-absorption in an array of detectors. This array consists of 217 well-type phoswich detector cells (PDCs) surrounded by a side anti-coincidence shield (SAS) composed of 54 segments of BGO crystals. At balloon altitude, the intensity of backgrounds due to cosmic-ray charged particles, atmospheric gamma-rays and neutrons is extremely high, typically a few hundred Hz per unit. Hence the data acquisition (DAQ) system of PoGOLite is required to handle more than 270 signals simultaneously, and detect weak signals from astrophysical objects (100mCrab, 1.5 cs(-1) in 25-80 keV) under such a severe environment. We have developed a new DAQ system consisting of front-end electronics, waveform digitizer, Field Programmable Gate Array (FPGA) and a microprocessor. In this system, all output signals of PDC / SAS are fed into individual charge-sensitive amplifier and then digitized to 12 bit accuracy at 24 MSa/s by pipelined analog to digital converters. A DAQ board for the PDC records waveforms which will be examined in an off-line analysis to distinguish signals from the background events and measure the energy spectrum and polarization of targets. A board for the SAS records hit pattern to be used for background rejection. It also continuously records a pulse-height analysis (PHA) histogram to monitor incident background flux. These basic functions of the DAQ system were verified in a series of beam tests.
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| 557. |
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| 558. |
- Tsiantoulas, D., et al.
(author)
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APRIL limits atherosclerosis by binding to heparan sulfate proteoglycans
- 2021
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 597, s. 92-96
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Journal article (peer-reviewed)abstract
- Atherosclerotic cardiovascular disease causes heart attacks and strokes, which are the leading causes of mortality worldwide(1). The formation of atherosclerotic plaques is initiated when low-density lipoproteins bind to heparan-sulfate proteoglycans (HSPGs)(2) and become trapped in the subendothelial space of large and medium size arteries, which leads to chronic inflammation and remodelling of the artery wall(2). A proliferation-inducing ligand (APRIL) is a cytokine that binds to HSPGs(3), but the physiology of this interaction is largely unknown. Here we show that genetic ablation or antibody-mediated depletion of APRIL aggravates atherosclerosis in mice. Mechanistically, we demonstrate that APRIL confers atheroprotection by binding to heparan sulfate chains of heparan-sulfate proteoglycan 2 (HSPG2), which limits the retention of low-density lipoproteins, accumulation of macrophages and formation of necrotic cores. Indeed, antibody-mediated depletion of APRIL in mice expressing heparan sulfate-deficient HSPG2 had no effect on the development of atherosclerosis. Treatment with a specific anti-APRIL antibody that promotes the binding of APRIL to HSPGs reduced experimental atherosclerosis. Furthermore, the serum levels of a form of human APRIL protein that binds to HSPGs, which we termed non-canonical APRIL (nc-APRIL), are associated independently of traditional risk factors with long-term cardiovascular mortality in patients with atherosclerosis. Our data reveal properties of APRIL that have broad pathophysiological implications for vascular homeostasis.
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| 559. |
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| 560. |
- Wernly, B, et al.
(author)
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Anti-CD3 Antibody Treatment Reduces Scar Formation in a Rat Model of Myocardial Infarction
- 2020
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In: Cells. - : MDPI AG. - 2073-4409. ; 9:2
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Journal article (peer-reviewed)abstract
- Introduction: Antibody treatment with anti-thymocyte globulin (ATG) has been shown to be cardioprotective. We aimed to evaluate which single anti-T-cell epitope antibody alters chemokine expression at a level similar to ATG and identified CD3, which is a T-cell co-receptor mediating T-cell activation. Based on these results, the effects of anti-CD3 antibody treatment on angiogenesis and cardioprotection were tested in vitro and in vivo. Methods: Concentrations of IL-8 and MCP-1 in supernatants of human peripheral blood mononuclear cell (PBMC) cultures following distinct antibody treatments were evaluated by Enzyme-linked Immunosorbent Assay (ELISA). In vivo, anti-CD3 antibodies or vehicle were injected intravenously in rats subjected to acute myocardial infarction (AMI). Chemotaxis and angiogenesis were evaluated using tube and migration assays. Intracellular pathways were assessed using Western blot. Extracellular vesicles (EVs) were quantitatively evaluated using fluorescence-activated cell scanning, exoELISA, and nanoparticle tracking analysis. Also, microRNA profiles were determined by next-generation sequencing. Results: Only PBMC stimulation with anti-CD3 antibody led to IL-8 and MCP-1 changes in secretion, similar to ATG. In a rat model of AMI, systemic treatment with an anti-CD3 antibody markedly reduced infarct scar size (27.8% (Inter-quartile range; IQR 16.2–34.9) vs. 12.6% (IQR 8.3–27.2); p < 0.01). The secretomes of anti-CD3 treated PBMC neither induced cardioprotective pathways in cardiomyocytes nor pro-angiogenic mechanisms in human umbilical vein endothelial cell (HUVECs) in vitro. While EVs quantities remained unchanged, PBMC incubation with an anti-CD3 antibody led to alterations in EVs miRNA expression. Conclusion: Treatment with an anti-CD3 antibody led to decreased scar size in a rat model of AMI. Whereas cardioprotective and pro-angiogenetic pathways were unaltered by anti-CD3 treatment, qualitative changes in the EVs miRNA expression could be observed, which might be causal for the observed cardioprotective phenotype. We provide evidence that EVs are a potential cardioprotective treatment target. Our findings will also provide the basis for a more detailed analysis of putatively relevant miRNA candidates.
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