Dopamine induces the accumulation of insoluble prion protein and affects autophagic flux

Accumulation of protein aggregates is a histopathological hallmark of several neurodegenerative diseases, but in most cases the aggregation occurs without defined mutations or clinical histories, suggesting that certain endogenous metabolites can promote aggregation of specific proteins. One example that supports this hypothesis is dopamine and its metabolites. Dopamine metabolism generates several oxidative metabolites that induce aggregation of alpha-synuclein, and represents the main etiology of Parkinson's diseases. Because dopamine and its metabolites are unstable and can be highly reactive, we investigated whether these molecules can also affect other proteins that are prone to aggregate, such as cellular prion protein (PrPC). in this study, we showed that dopamine treatment of neuronal cells reduced the number of viable cells and increased the production of reactive oxygen species (ROS) as demonstrated in previous studies. Overall PrPC expression level was not altered by dopamine treatment, but its unglycosylated form was consistently reduced at 100 mu M of dopamine. At the same concentration, the level of phosphorylated mTOR and 4EBP1 was also reduced. Moreover, dopamine treatment decreased the solubility of PrPC, and increased its accumulation in autophagosomal compartments with concomitant induction of LC3-II and p62/SQSTM1 levels. in vitro oxidation of dopamine promoted formation of high-order oligomers of recombinant prion protein. These results suggest that dopamine metabolites alter the conformation of PrPC, which in turn is sorted to degradation pathway, causing autophagosome overload and attenuation of protein synthesis. Accumulation of PrPC aggregates is an important feature of prion diseases. Thus, this study brings new insight into the dopamine metabolism as a source of endogenous metabolites capable of altering PrPC solubility and its subcellular localization.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)EMU (programa de equipamentos multiusuarios)Universidade Federal de São Paulo, Dept Biochem Mol & Cell Biol, BR-04039032 São Paulo, BrazilUniv Metodista São Paulo, São Paulo, BrazilAC Camargo Canc Ctr, Int Res Ctr, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biophys, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biochem Mol & Cell Biol, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biophys, BR-04039032 São Paulo, BrazilFAPESP: 2008/06152-9FAPESP: 2009/14027-2FAPESP: 2013/22413-5FAPESP: 2012/18093-2Web of Scienc

Wide-Field Imaging and Polarimetry for the Biggest and Brightest in the 20GHz Southern Sky

We present wide-field imaging and polarimetry at 20GHz of seven of the most extended, bright (Stot >= 0.50 Jy), high-frequency selected radio sources in the southern sky with declinations < -30 deg. Accompanying the data are brief reviews of the literature for each source, The results presented here aid in the statistical completeness of the Australia Telescope 20GHz Survey's bright source sample. The data are of crucial interest for future cosmic microwave background missions as a collection of information about candidate calibrator sources. We are able to obtain data for seven of the nine sources identified by our selection criteria. We report that Pictor A is thus far the best extragalactic calibrator candidate for the Low Frequency Instrument of the Planck European Space Agency mission due to its high level of integrated polarized flux density (0.50+/-0.06 Jy) on a scale of 10 arcmin. Six of the seven sources have a clearly detected compact radio core, with either a null or less than two percent detection of polarized emission from the nucleus. Most sources with detected jets have magnetic field alignments running in a longitudinal configuration, however PKS1333-33 exhibits transverse fields and an orthogonal change in field geometry from nucleus to jets.Comment: 17 pages, 9 figures, 2 table

Galactic and Extragalactic Samples of Supernova Remnants: How They Are Identified and What They Tell Us

Supernova remnants (SNRs) arise from the interaction between the ejecta of a supernova (SN) explosion and the surrounding circumstellar and interstellar medium. Some SNRs, mostly nearby SNRs, can be studied in great detail. However, to understand SNRs as a whole, large samples of SNRs must be assembled and studied. Here, we describe the radio, optical, and X-ray techniques which have been used to identify and characterize almost 300 Galactic SNRs and more than 1200 extragalactic SNRs. We then discuss which types of SNRs are being found and which are not. We examine the degree to which the luminosity functions, surface-brightness distributions and multi-wavelength comparisons of the samples can be interpreted to determine the class properties of SNRs and describe efforts to establish the type of SN explosion associated with a SNR. We conclude that in order to better understand the class properties of SNRs, it is more important to study (and obtain additional data on) the SNRs in galaxies with extant samples at multiple wavelength bands than it is to obtain samples of SNRs in other galaxiesComment: Final 2016 draft of a chapter in "Handbook of Supernovae" edited by Athem W. Alsabti and Paul Murdin. Final version available at https://doi.org/10.1007/978-3-319-20794-0_90-

Search for High Mass Photon Pairs in p-pbar --> gamma-gamma-jet-jet Events at sqrt(s)=1.8 TeV

A search has been carried out for events in the channel p-barp --> gamma gamma jet jet. Such a signature can characterize the production of a non-standard Higgs boson together with a W or Z boson. We refer to this non-standard Higgs, having standard model couplings to vector bosons but no coupling to fermions, as a "bosonic Higgs." With the requirement of two high transverse energy photons and two jets, the diphoton mass (m(gamma gamma)) distribution is consistent with expected background. A 90(95)% C.L. upper limit on the cross section as a function of mass is calculated, ranging from 0.60(0.80) pb for m(gamma gamma) = 65 GeV/c^2 to 0.26(0.34) pb for m(gamma gamma) = 150 GeV/c^2, corresponding to a 95% C.L. lower limit on the mass of a bosonic Higgs of 78.5 GeV/c^2.Comment: 9 pages, 3 figures. Replacement has new H->gamma gamma branching ratios and corresponding new mass limit

Search For Heavy Pointlike Dirac Monopoles

We have searched for central production of a pair of photons with high transverse energies in $p\bar p$ collisions at $\sqrt{s} = 1.8$ TeV using $70 pb^{-1}$ of data collected with the D\O detector at the Fermilab Tevatron in 1994--1996. If they exist, virtual heavy pointlike Dirac monopoles could rescatter pairs of nearly real photons into this final state via a box diagram. We observe no excess of events above background, and set lower 95% C.L. limits of $610, 870, or 1580 GeV/c^2$ on the mass of a spin 0, 1/2, or 1 Dirac monopole.Comment: 12 pages, 4 figure

Direct Search for Charged Higgs Bosons in Decays of Top Quarks

We present a search for charged Higgs bosons in decays of pair-produced top quarks in pbar p collisions at sqrt(s) = 1.8 TeV using 62.2 pb^-1 of data recorded by the D0 detector at the Fermilab Tevatron collider. No evidence is found for signal, and we exclude at 95% confidence most regions of the (M higgs, tan beta) parameter space where the decay t->H b has a branching fraction greater than 0.36 and B(H -> tau nu) is large.Comment: 11 pages, 4 figures, submitted to Phys. Rev. Let

Ratio of the Isolated Photon Cross Sections at \sqrt{s} = 630 and 1800 GeV

The inclusive cross section for production of isolated photons has been measured in \pbarp collisions at $\sqrt{s} = 630$ GeV with the \D0 detector at the Fermilab Tevatron Collider. The photons span a transverse energy ($E_T$) range from 7-49 GeV and have pseudorapidity $|\eta| < 2.5$. This measurement is combined with to previous \D0 result at $\sqrt{s} = 1800$ GeV to form a ratio of the cross sections. Comparison of next-to-leading order QCD with the measured cross section at 630 GeV and ratio of cross sections show satisfactory agreement in most of the $E_T$ range.Comment: 7 pages. Published in Phys. Rev. Lett. 87, 251805, (2001

Limits on Anomalous WWgamma and WWZ Couplings

Limits on the anomalous WWgamma and WWZ couplings are presented from a simultaneous fit to the data samples of three gauge boson pair final states in pbar-p collisions at sqrt(s)=1.8 TeV: Wgamma production with the W boson decaying to enu or munu, W boson pair production with both of the W bosons decaying to enu or munu, and WW or WZ production with one W boson decaying to enu and the other W boson or the Z boson decaying to two jets. Assuming identical WWgamma and WWZ couplings, 95 % C.L. limits on the anomalous couplings of -0.30<Delta kappa<0.43 (lambda = 0) and -0.20<lambda<0.20 (Delta kappa = 0) are obtained using a form factor scale Lambda = 2.0 TeV. Limits found under other assumptions on the relationship between the WWgamma and WWZ couplings are also presented.Comment: 13 pages, 3 figures, submitted to Physical Review

Search for Top Squark Pair Production in the Dielectron Channel

This report describes the first search for top squark pair production in the channel stop_1 stopbar_1 -> b bbar chargino_1 chargino_1 -> ee+jets+MEt using 74.9 +- 8.9 pb^-1 of data collected using the D0 detector. A 95% confidence level upper limit on sigma*B is presented. The limit is above the theoretical expectation for sigma*B for this process, but does show the sensitivity of the current D0 data set to a particular topology for new physics.Comment: Five pages, including three figures, submitted to PRD Brief Report

Search for First Generation Scalar Leptoquark Pairs in ppbar Collisions at sqrt(s)=1.8 TeV

We have searched for first generation scalar leptoquark (LQ) pairs in the enu+jets channel using ppbar collider data (integrated luminosity= 115 pb^-1) collected by the DZero experiment at the Fermilab Tevatron during 1992-96. The analysis yields no candidate events. We combine the results with those from the ee+jets and nunu+jets channels to obtain 95% confidence level (CL) upper limits on the LQ pair production cross section as a function of mass and of beta, the branching fraction to a charged lepton. Comparing with the next-to-leading order theory, we set 95% CL lower limits on the LQ mass of 225, 204, and 79 GeV/c^2 for beta=1, 1/2, and 0, respectively.Comment: 14 pages, 4 figures, submitted to Physical Review Letters Replaced to correct visitor addresse