Involvement of the Choroid Plexus in the Pathogenesis of Niemann-Pick Disease Type C

Niemann-Pick type C (NPC) disease, sometimes called childhood Alzheimer's, is a rare neurovisceral lipid storage disease with progressive neurodegeneration leading to premature death. The disease is caused by loss-of-function mutations in the Npc1 or Npc2 gene which both result into lipid accumulation in the late endosomes and lysosomes. Since the disease presents with a broad heterogenous clinical spectrum, the involved disease mechanisms are still incompletely understood and this hampers finding an effective treatment. As NPC patients, who carry NPC1 mutations, have shown to share several pathological features with Alzheimer's disease (AD) and we and others have previously shown that AD is associated with a dysfunctionality of the blood-cerebrospinal fluid (CSF) barrier located at choroid plexus, we investigated the functionality of this latter barrier in NPC1 pathology. Using NPC1-/- mice, we show that despite an increase in inflammatory gene expression in choroid plexus epithelial (CPE) cells, the blood-CSF barrier integrity is not dramatically affected. Interestingly, we did observe a massive increase in autophagosomes in CPE cells and enlarged extracellular vesicles (EVs) in CSF upon NPC1 pathology. Additionally, we revealed that these EVs exert toxic effects on brain tissue, in vitro as well as in vivo. Moreover, we observed that EVs derived from the supernatant of NPC1-/- choroid plexus explants are able to induce typical brain pathology characteristics of NPC1-/-, more specifically microgliosis and astrogliosis. Taken together, our data reveal for the first time that the choroid plexus and CSF EVs might play a role in the brain-related pathogenesis of NPC1

Human transmission of blastocystis by fecal microbiota transplantation without development of gastrointestinal symptoms in recipients

Background. Patients with multiple recurrent Clostridioides difficile infections (rCDI) are treated with fecal microbiota transplantation (FMT), using feces provided by healthy donors. Blastocystis colonization of donors is considered an exclusion criterion, whereas its pathogenicity is still under debate. Methods. The introduction of molecular screening for Blastocystis sp. at our stool bank identified 2 donors with prior negative microscopies but positive polymerase chain reactions (PCRs). Potential transmission of Blastocystis sp. to patients was assessed on 16 fecal patient samples, pre- and post-FMT, by PCR and subtype (ST) analyses. In addition, clinical outcomes for the treatment of rCDI (n = 31), as well as the development of gastrointestinal symptoms, were assessed. Results. There was 1 donor who carried Blastocystis ST1, and the other contained ST3. All patients tested negative for Blastocystis prior to FMT. With a median diagnosis at 20.5 days after FMT, 8 of 16 (50%) patients developed intestinal colonization with Blastocystis, with identical ST sequences as their respective donors. Blastocystis-containing fecal suspensions were used to treat 31 rCDI patients, with an FMT success rate of 84%. This success rate was not statistically different from patients transferred with Blastocystis sp.–negative donor feces (93%, 76/82). Patients transferred with Blastocystis sp.–positive donor feces did not report any significant differences in bowel complaints in the first week, after 3 weeks, or

Effect of event selection on jetlike correlation measurement in d+Au collisions at sNN=200 GeV

AbstractDihadron correlations are analyzed in sNN=200 GeV d+Au collisions classified by forward charged particle multiplicity and zero-degree neutral energy in the Au-beam direction. It is found that the jetlike correlated yield increases with the event multiplicity. After taking into account this dependence, the non-jet contribution on the away side is minimal, leaving little room for a back-to-back ridge in these collisions

Beam-energy Dependence Of Charge Balance Functions From Au + Au Collisions At Energies Available At The Bnl Relativistic Heavy Ion Collider

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Balance functions have been measured in terms of relative pseudorapidity (Δη) for charged particle pairs at the BNL Relativistic Heavy Ion Collider from Au + Au collisions at sNN=7.7GeV to 200 GeV using the STAR detector. These results are compared with balance functions measured at the CERN Large Hadron Collider from Pb + Pb collisions at sNN=2.76TeV by the ALICE Collaboration. The width of the balance function decreases as the collisions become more central and as the beam energy is increased. In contrast, the widths of the balance functions calculated using shuffled events show little dependence on centrality or beam energy and are larger than the observed widths. Balance function widths calculated using events generated by UrQMD are wider than the measured widths in central collisions and show little centrality dependence. The measured widths of the balance functions in central collisions are consistent with the delayed hadronization of a deconfined quark gluon plasma (QGP). The narrowing of the balance function in central collisions at sNN=7.7 GeV implies that a QGP is still being created at this relatively low energy. © 2016 American Physical Society.942CNPq, Conselho Nacional de Desenvolvimento Científico e TecnológicoMinistry of Education and Science of the Russian FederationMOE, Ministry of Education of the People's Republic of ChinaMOST, Ministry of Science and Technology of the People's Republic of ChinaNRF-2012004024, National Research FoundationNSF, National Stroke FoundationConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Multi-wavelength observations of blazar AO 0235+164 in the 2008-2009 flaring state

The blazar AO 0235+164 (z = 0.94) has been one of the most active objects observed by Fermi Large Area Telescope (LAT) since its launch in Summer 2008. In addition to the continuous coverage by Fermi, contemporaneous observations were carried out from the radio to γ-ray bands between 2008 September and 2009 February. In this paper, we summarize the rich multi-wavelength data collected during the campaign (including F-GAMMA, GASP-WEBT, Kanata, OVRO, RXTE, SMARTS, Swift, and other instruments), examine the cross-correlation between the light curves measured in the different energy bands, and interpret the resulting spectral energy distributions in the context of well-known blazar emission models. We find that the γ-ray activity is well correlated with a series of near-IR/optical flares, accompanied by an increase in the optical polarization degree. On the other hand, the X-ray light curve shows a distinct 20 day high state of unusually soft spectrum, which does not match the extrapolation of the optical/UV synchrotron spectrum. We tentatively interpret this feature as the bulk Compton emission by cold electrons contained in the jet, which requires an accretion disk corona with an effective covering factor of 19% at a distance of 100 R g. We model the broadband spectra with a leptonic model with external radiation dominated by the infrared emission from the dusty torus. © 2012. The American Astronomical Society. All rights reserved

J/ψ Production At Low Pt In Au+au And Cu+cu Collisions At Snn =200 Gev With The Star Detector

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Dielectron Azimuthal Anisotropy At Mid-rapidity In Au+au Collisions At Snn =200 Gev

We report on the first measurement of the azimuthal anisotropy (v2) of dielectrons (e+e- pairs) at mid-rapidity from sNN=200 GeV Au+Au collisions with the STAR detector at the Relativistic Heavy Ion Collider (RHIC), presented as a function of transverse momentum (pT) for different invariant-mass regions. In the mass region Mee<1.1 GeV/c2 the dielectron v2 measurements are found to be consistent with expectations from π0,η,ω, and φ decay contributions. In the mass region 1.1<Mee<2.9GeV/c2, the measured dielectron v2 is consistent, within experimental uncertainties, with that from the cc¯ contributions.906Adams, J., (2005) Nucl. Phys. A, 757, p. 102. , NUPABL 0375-9474Arsene, I., (2005) Nucl. Phys. A, 757, p. 1. , NUPABL 0375-9474Adcox, K., (2005) Nucl. Phys. A, 757, p. 184. , NUPABL 0375-9474Back, B.B., (2005) Nucl. Phys. A, 757, p. 28. , NUPABL 0375-9474Rapp, R., Wambach, J., (2002) Adv. Nucl. Phys., 25, p. 1. , 0065-2970David, G., Rapp, R., Xu, Z., (2008) Phys. 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Beam-energy Dependence Of Charge Separation Along The Magnetic Field In Au+au Collisions At Rhic

Local parity-odd domains are theorized to form inside a quark-gluon plasma which has been produced in high-energy heavy-ion collisions. The local parity-odd domains manifest themselves as charge separation along the magnetic field axis via the chiral magnetic effect. The experimental observation of charge separation has previously been reported for heavy-ion collisions at the top RHIC energies. In this Letter, we present the results of the beam-energy dependence of the charge correlations in Au+Au collisions at midrapidity for center-of-mass energies of 7.7, 11.5, 19.6, 27, 39, and 62.4 GeV from the STAR experiment. After background subtraction, the signal gradually reduces with decreased beam energy and tends to vanish by 7.7 GeV. 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Insights into the high-energy γ-ray emission of Markarian 501 from extensive multifrequency observations in the Fermi era

We report on the γ-ray activity of the blazar Mrk 501 during the first 480 days of Fermi operation. We find that the average Large Area Telescope (LAT) γ-ray spectrum of Mrk 501 can be well described by a single power-law function with a photon index of 1.78 ± 0.03. While we observe relatively mild flux variations with the Fermi-LAT (within less than a factor of two), we detect remarkable spectral variability where the hardest observed spectral index within the LAT energy range is 1.52 ± 0.14, and the softest one is 2.51 ± 0.20. These unexpected spectral changes do not correlate with the measured flux variations above 0.3 GeV. In this paper, we also present the first results from the 4.5 month long multifrequency campaign (2009 March 15-August 1) on Mrk 501, which included the Very Long Baseline Array (VLBA), Swift, RXTE, MAGIC, and VERITAS, the F-GAMMA, GASP-WEBT, and other collaborations and instruments which provided excellent temporal and energy coverage of the source throughout the entire campaign. The extensive radio to TeV data set from this campaign provides us with the most detailed spectral energy distribution yet collected for this source during its relatively low activity. The average spectral energy distribution of Mrk 501 is well described by the standard one-zone synchrotron self-Compton (SSC) model. In the framework of this model, we find that the dominant emission region is characterized by a size ≲0.1 pc (comparable within a factor of few to the size of the partially resolved VLBA core at 15-43 GHz), and that the total jet power (≃1044 erg s-1) constitutes only a small fraction (∼10-3) of the Eddington luminosity. The energy distribution of the freshly accelerated radiating electrons required to fit the time-averaged data has a broken power-law form in the energy range 0.3 GeV-10 TeV, with spectral indices 2.2 and 2.7 below and above the break energy of 20 GeV. We argue that such a form is consistent with a scenario in which the bulk of the energy dissipation within the dominant emission zone of Mrk 501 is due to relativistic, proton-mediated shocks. We find that the ultrarelativistic electrons and mildly relativistic protons within the blazar zone, if comparable in number, are in approximate energy equipartition, with their energy dominating the jet magnetic field energy by about two orders of magnitude. © 2011. The American Astronomical Society

Search for single vector-like B quark production and decay via B → bH(b¯b) in pp collisions at √s = 13 TeV with the ATLAS detector

A search is presented for single production of a vector-like B quark decaying into a Standard Model b-quark and a Standard Model Higgs boson, which decays into a b¯b pair. The search is carried out in 139 fb−1 of √s = 13 TeV proton-proton collision data collected by the ATLAS detector at the LHC between 2015 and 2018. No significant deviation from the Standard Model background prediction is observed, and mass-dependent exclusion limits at the 95% confidence level are set on the resonance production cross-section in several theoretical scenarios determined by the couplings cW, cZ and cH between the B quark and the Standard Model W, Z and Higgs bosons, respectively. For a vector-like B occurring as an isospin singlet, the search excludes values of cW greater than 0.45 for a B resonance mass (mB) between 1.0 and 1.2 TeV. For 1.2 TeV < mB < 2.0 TeV, cW values larger than 0.50–0.65 are excluded. If the B occurs as part of a (B, Y) doublet, the smallest excluded cZ coupling values range between 0.3 and 0.5 across the investigated resonance mass range 1.0 TeV < mB < 2.0 TeV