3,419 research outputs found

    Regulation of caspase-3 processing by cIAP2 controls the switch between pro-inflammatory activation and cell death in microglia.

    Get PDF
    Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International Licence. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons licence, users will need to obtain permission from the licence holder to reproduce the material.The activation of microglia, resident immune cells of the central nervous system, and inflammation-mediated neurotoxicity are typical features of neurodegenerative diseases, for example, Alzheimer's and Parkinson's diseases. An unexpected role of caspase-3, commonly known to have executioner role for apoptosis, was uncovered in the microglia activation process. A central question emerging from this finding is what prevents caspase-3 during the microglia activation from killing those cells? Caspase-3 activation occurs as a two-step process, where the zymogen is first cleaved by upstream caspases, such as caspase-8, to form intermediate, yet still active, p19/p12 complex; thereafter, autocatalytic processing generates the fully mature p17/p12 form of the enzyme. Here, we show that the induction of cellular inhibitor of apoptosis protein 2 (cIAP2) expression upon microglia activation prevents the conversion of caspase-3 p19 subunit to p17 subunit and is responsible for restraining caspase-3 in terms of activity and subcellular localization. We demonstrate that counteracting the repressive effect of cIAP2 on caspase-3 activation, using small interfering RNA targeting cIAP2 or a SMAC mimetic such as the BV6 compound, reduced the pro-inflammatory activation of microglia cells and promoted their death. We propose that the different caspase-3 functions in microglia, and potentially other cell types, reside in the active caspase-3 complexes formed. These results also could indicate cIAP2 as a possible therapeutic target to modulate microglia pro-inflammatory activation and associated neurotoxicity observed in neurodegenerative disorders

    First observation of psi(2S)-->K_S K_L

    Full text link
    The decay psi(2S)-->K_S K_L is observed for the first time using psi(2S) data collected with the Beijing Spectrometer (BESII) at the Beijing Electron Positron Collider (BEPC); the branching ratio is determined to be B(psi(2S)-->K_S K_L) = (5.24\pm 0.47 \pm 0.48)\times 10^{-5}. Compared with J/psi-->K_S K_L, the psi(2S) branching ratio is enhanced relative to the prediction of the perturbative QCD ``12%'' rule. The result, together with the branching ratios of psi(2S) decays to other pseudoscalar meson pairs (\pi^+\pi^- and K^+K^-), is used to investigate the relative phase between the three-gluon and the one-photon annihilation amplitudes of psi(2S) decays.Comment: 5 pages, 4 figures, 2 tables, submitted to Phys. Rev. Let

    Gene and protein expression of glucose transporter 1 and glucose transporter 3 in human laryngeal cancer—the relationship with regulatory hypoxia-inducible factor-1α expression, tumor invasiveness, and patient prognosis

    Get PDF
    Increased glucose uptake mediated by glucose transporters and reliance on glycolysis are common features of malignant cells. Hypoxia-inducible factor-1α supports the adaptation of hypoxic cells by inducing genes related to glucose metabolism. The contribution of glucose transporter (GLUT) and hypoxia-inducible factor-1α (HIF-1α) activity to tumor behavior and their prognostic value in head and neck cancers remains unclear. The aim of this study was to examine the predictive value of GLUT1, GLUT3, and HIF-1α messenger RNA (mRNA)/protein expression as markers of tumor aggressiveness and prognosis in laryngeal cancer. The level of hypoxia/metabolic marker genes was determined in 106 squamous cell laryngeal cancer (SCC) and 73 noncancerous matched mucosa (NCM) controls using quantitative realtime PCR. The related protein levels were analyzed by Western blot. Positive expression of SLC2A1, SLC2A3, and HIF-1α genes was noted in 83.9, 82.1, and 71.7 % of SCC specimens and in 34.4, 59.4, and 62.5 % of laryngeal cancer samples. Higher levels of mRNA/protein for GLUT1 and HIF-1α were noted in SCC compared to NCM (p<0.05). SLC2A1 was found to have a positive relationship with grade, tumor front grading (TFG) score, and depth and mode of invasion (p<0.05). SLC2A3 was related to grade and invasion type (p<0.05). There were also relationships of HIF-1α with pTNM, TFG scale, invasion depth and mode, tumor recurrences, and overall survival (p<0.05). In addition, more advanced tumors were found to be more likely to demonstrate positive expression of these proteins. In conclusion, the hypoxia/metabolic markers studied could be used as molecular markers of tumor invasiveness in laryngeal cancer.This work was supported, in part, by the statutory fund of the Department of Cytobiochemistry, University of Łódź, Poland (506/811), and by grant fromtheNational Science Council, Poland (N403 043 32/2326)

    Study of psi(2S) decays to X J/psi

    Full text link
    Using J/psi -> mu^+ mu^- decays from a sample of approximately 4 million psi(2S) events collected with the BESI detector, the branching fractions of psi(2S) -> eta J/psi, pi^0 pi^0 J/psi, and anything J/psi normalized to that of psi(2S) -> pi^+ pi^- J/psi are measured. The results are B(psi(2S) -> eta J/psi)/B(psi(2S) -> pi^+ pi^- J/psi) = 0.098 \pm 0.005 \pm 0.010, B(psi(2S) -> pi^0 pi^0 J/psi)/B(psi(2S) -> pi^+ pi^- J/psi) = 0.570 \pm 0.009 \pm 0.026, and B(psi(2S) -> anything J/psi)/B(psi(2S) -> pi^+ pi^- J/psi) = 1.867 \pm 0.026 \pm 0.055.Comment: 13 pages, 8 figure

    Asymmetric Origin for Gravitino Relic Density in the Hybrid Gravity-Gauge Mediated Supersymmetry Breaking

    Get PDF
    We propose the hybrid gravity-gauge mediated supersymmetry breaking where the gravitino mass is about several GeV. The strong constraints on supersymmetry viable parameter space from the CMS and ATLAS experiments at the LHC can be relaxed due to the heavy colored supersymmetric particles, and it is consistent with null results in the dark matter (DM) direct search experiments such as XENON100. In particular, the possible maximal flavor and CP violations from the relatively small gravity mediation may naturally account for the recent LHCb anomaly. In addition, because the gravitino mass is around the asymmetric DM mass, we propose the asymmetric origin of the gravitino relic density and solve the cosmological coincident problem on the DM and baryon densities \Omega_{\rm DM}:\Omega_{B}\approx 5:1. The gravitino relic density arises from asymmetric metastable particle (AMP) late decay. However, we show that there is no AMP candidate in the minimal supersymmetric Standard Model (SM) due to the robust gaugino/Higgsino mediated wash-out effects. Interestingly, AMP can be realized in the well motivated supersymmetric SMs with vector-like particles or continuous U(1)_R symmetry. Especially, the lightest CP-even Higgs boson mass can be lifted in the supersymmetric SMs with vector-like particles.Comment: RevTex4, 21 pages, 1 figure, minor corrections, JHEP versio

    The extraordinary evolutionary history of the reticuloendotheliosis viruses

    Get PDF
    The reticuloendotheliosis viruses (REVs) comprise several closely related amphotropic retroviruses isolated from birds. These viruses exhibit several highly unusual characteristics that have not so far been adequately explained, including their extremely close relationship to mammalian retroviruses, and their presence as endogenous sequences within the genomes of certain large DNA viruses. We present evidence for an iatrogenic origin of REVs that accounts for these phenomena. Firstly, we identify endogenous retroviral fossils in mammalian genomes that share a unique recombinant structure with REVs—unequivocally demonstrating that REVs derive directly from mammalian retroviruses. Secondly, through sequencing of archived REV isolates, we confirm that contaminated Plasmodium lophurae stocks have been the source of multiple REV outbreaks in experimentally infected birds. Finally, we show that both phylogenetic and historical evidence support a scenario wherein REVs originated as mammalian retroviruses that were accidentally introduced into avian hosts in the late 1930s, during experimental studies of P. lophurae, and subsequently integrated into the fowlpox virus (FWPV) and gallid herpesvirus type 2 (GHV-2) genomes, generating recombinant DNA viruses that now circulate in wild birds and poultry. Our findings provide a novel perspective on the origin and evolution of REV, and indicate that horizontal gene transfer between virus families can expand the impact of iatrogenic transmission events

    Measurement of the Branching Fraction of J/psi --> pi+ pi- pi0

    Full text link
    Using 58 million J/psi and 14 million psi' decays obtained by the BESII experiment, the branching fraction of J/psi --> pi+ pi- pi0 is determined. The result is (2.10+/-0.12)X10^{-2}, which is significantly higher than previous measurements.Comment: 9 pages, 8 figures, RevTex

    Resonances in J/ψϕπ+πJ/\psi \to \phi \pi ^+\pi ^- and ϕK+K\phi K^+K^-

    Full text link
    A partial wave analysis is presented of J/ψϕπ+πJ/\psi \to \phi \pi ^+\pi ^- and ϕK+K\phi K^+K^- from a sample of 58M J/ψJ/\psi events in the BES II detector. The f0(980)f_0(980) is observed clearly in both sets of data, and parameters of the Flatt\' e formula are determined accurately: M=965±8M = 965 \pm 8 (stat) ±6\pm 6 (syst) MeV/c2^2, g1=165±10±15g_1 = 165 \pm 10 \pm 15 MeV/c2^2, g2/g1=4.21±0.25±0.21g_2/g_1 = 4.21 \pm 0.25 \pm 0.21. The ϕππ\phi \pi \pi data also exhibit a strong ππ\pi \pi peak centred at M=1335M = 1335 MeV/c2^2. It may be fitted with f2(1270)f_2(1270) and a dominant 0+0^+ signal made from f0(1370)f_0(1370) interfering with a smaller f0(1500)f_0(1500) component. There is evidence that the f0(1370)f_0(1370) signal is resonant, from interference with f2(1270)f_2(1270). There is also a state in ππ\pi \pi with M=179030+40M = 1790 ^{+40}_{-30} MeV/c2^2 and Γ=27030+60\Gamma = 270 ^{+60}_{-30} MeV/c2^2; spin 0 is preferred over spin 2. This state, f0(1790)f_0(1790), is distinct from f0(1710)f_0(1710). The ϕKKˉ\phi K\bar K data contain a strong peak due to f2(1525)f_2'(1525). A shoulder on its upper side may be fitted by interference between f0(1500)f_0(1500) and f0(1710)f_0(1710).Comment: 17 pages, 6 figures, 1 table. Submitted to Phys. Lett.
    corecore