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Sample records for earth skimming tau

  1. Tau energy loss and ultrahigh energy skimming tau neutrinos

    NASA Astrophysics Data System (ADS)

    Jeong, Yu Seon; Luu, Minh Vu; Reno, Mary Hall; Sarcevic, Ina

    2017-08-01

    We consider propagation of high-energy earth-skimming taus produced in interactions of astrophysical tau neutrinos. For astrophysical tau neutrinos, we take generic power-law flux, E-2 and the cosmogenic flux initiated by the protons. We calculate tau energy loss in several approaches, such as dipole models and the phenomenological approach in which parametrization of the F2 is used. We evaluate the tau neutrino charged-current cross section using the same approaches for consistency. We find that uncertainty in the neutrino cross section and in the tau energy loss partially compensate giving very small theoretical uncertainty in the emerging tau flux for distances ranging from 2 to 100 km and for the energy range between 1 06 and 1 011 GeV , focusing on energies above 1 08 GeV . When we consider uncertainties in the neutrino cross section, inelasticity in neutrino interactions and the tau energy loss, which are not correlated, i.e. they are not all calculated in the same approach, theoretical uncertainty ranges from about 30% and 60% at 1 08 GeV to about factors of 3.3 and 3.8 at 1 011 GeV for the E-2 flux and the cosmogenic flux, respectively, for the distance of 10 km rock. The spread in predictions significantly increases for much larger distances, e.g., ˜1 ,000 km . Most of the uncertainty comes from the treatment of photonuclear interactions of the tau in transit through large distances. We also consider Monte Carlo calculation of the tau propagation and we find that the result for the emerging tau flux is in agreement with the result obtained using analytic approach. Our results are relevant to several experiments that are looking for skimming astrophysical taus, such as the Pierre Auger Observatory, HAWC and Ashra. We evaluate the aperture for the Auger and discuss briefly application to the other two experiments.

  2. Observability of Earth-Skimming Ultrahigh Energy Neutrinos

    NASA Astrophysics Data System (ADS)

    Feng, Jonathan L.; Fisher, Peter; Wilczek, Frank; Yu, Terri M.

    2002-04-01

    Neutrinos with energies above 108 GeV are expected from cosmic ray interactions with the microwave background and are predicted in many speculative models. Such energetic neutrinos are difficult to detect, as they are shadowed by Earth, but rarely interact in the atmosphere. Here we propose a novel detection strategy: Earth-skimming neutrinos convert to charged leptons that escape Earth, and these leptons are detected in ground level fluorescence detectors. With the existing HiRes detector, neutrinos from some proposed sources are marginally detectable, and improvements of 2 orders of magnitude are possible at the proposed Telescope Array.

  3. Upper limit on the diffuse flux of ultrahigh energy tau neutrinos from the Pierre Auger Observatory.

    PubMed

    Abraham, J; Abreu, P; Aglietta, M; Aguirre, C; Allard, D; Allekotte, I; Allen, J; Allison, P; Alvarez-Muñiz, J; Ambrosio, M; Anchordoqui, L; Andringa, S; Anzalone, A; Aramo, C; Argirò, S; Arisaka, K; Armengaud, E; Arneodo, F; Arqueros, F; Asch, T; Asorey, H; Assis, P; Atulugama, B S; Aublin, J; Ave, M; Avila, G; Bäcker, T; Badagnani, D; Barbosa, A F; Barnhill, D; Barroso, S L C; Bauleo, P; Beatty, J J; Beau, T; Becker, B R; Becker, K H; Bellido, J A; BenZvi, S; Berat, C; Bergmann, T; Bernardini, P; Bertou, X; Biermann, P L; Billoir, P; Blanch-Bigas, O; Blanco, F; Blasi, P; Bleve, C; Blümer, H; Bohácová, M; Bonifazi, C; Bonino, R; Boratav, M; Brack, J; Brogueira, P; Brown, W C; Buchholz, P; Bueno, A; Burton, R E; Busca, N G; Caballero-Mora, K S; Cai, B; Camin, D V; Caramete, L; Caruso, R; Carvalho, W; Castellina, A; Catalano, O; Cataldi, G; Cazon, L; Cester, R; Chauvin, J; Chiavassa, A; Chinellato, J A; Chou, A; Chye, J; Clark, P D J; Clay, R W; Colombo, E; Conceição, R; Connolly, B; Contreras, F; Coppens, J; Cordier, A; Cotti, U; Coutu, S; Covault, C E; Creusot, A; Criss, A; Cronin, J; Curutiu, A; Dagoret-Campagne, S; Daumiller, K; Dawson, B R; de Almeida, R M; De Donato, C; de Jong, S J; De La Vega, G; de Mello Junior, W J M; de Mello Neto, J R T; DeMitri, I; de Souza, V; del Peral, L; Deligny, O; Della Selva, A; Delle Fratte, C; Dembinski, H; Di Giulio, C; Diaz, J C; Dobrigkeit, C; D'Olivo, J C; Dornic, D; Dorofeev, A; dos Anjos, J C; Dova, M T; D'Urso, D; Dutan, I; DuVernois, M A; Engel, R; Epele, L; Erdmann, M; Escobar, C O; Etchegoyen, A; Facal San Luis, P; Falcke, H; Farrar, G; Fauth, A C; Fazzini, N; Ferrer, F; Ferry, S; Fick, B; Filevich, A; Filipcic, A; Fleck, I; Fonte, R; Fracchiolla, C E; Fulgione, W; García, B; García Gámez, D; Garcia-Pinto, D; Garrido, X; Geenen, H; Gelmini, G; Gemmeke, H; Ghia, P L; Giller, M; Glass, H; Gold, M S; Golup, G; Gomez Albarracin, F; Gómez Berisso, M; Gómez Herrero, R; Gonçalves, P; Gonçalves do Amaral, M; Gonzalez, D; Gonzalez, J G; González, M; Góra, D; Gorgi, A; Gouffon, P; Grassi, V; Grillo, A F; Grunfeld, C; Guardincerri, Y; Guarino, F; Guedes, G P; Gutiérrez, J; Hague, J D; Hamilton, J C; Hansen, P; Harari, D; Harmsma, S; Harton, J L; Haungs, A; Hauschildt, T; Healy, M D; Hebbeker, T; Hebrero, G; Heck, D; Hojvat, C; Holmes, V C; Homola, P; Hörandel, J; Horneffer, A; Horvat, M; Hrabovský, M; Huege, T; Hussain, M; Iarlori, M; Insolia, A; Ionita, F; Italiano, A; Kaducak, M; Kampert, K H; Karova, T; Kégl, B; Keilhauer, B; Kemp, E; Kieckhafer, R M; Klages, H O; Kleifges, M; Kleinfeller, J; Knapik, R; Knapp, J; Koang, D-H; Krieger, A; Krömer, O; Kuempel, D; Kunka, N; Kusenko, A; La Rosa, G; Lachaud, C; Lago, B L; Lebrun, D; Lebrun, P; Lee, J; Leigui de Oliveira, M A; Letessier-Selvon, A; Leuthold, M; Lhenry-Yvon, I; López, R; Lopez Agüera, A; Lozano Bahilo, J; Luna García, R; Maccarone, M C; Macolino, C; Maldera, S; Mancarella, G; Manceñido, M E; Mandat, D; Mantsch, P; Mariazzi, A G; Maris, I C; Marquez Falcon, H R; Martello, D; Martínez, J; Martínez Bravo, O; Mathes, H J; Matthews, J; Matthews, J A J; Matthiae, G; Maurizio, D; Mazur, P O; McCauley, T; McEwen, M; McNeil, R R; Medina, M C; Medina-Tanco, G; Meli, A; Melo, D; Menichetti, E; Menschikov, A; Meurer, Chr; Meyhandan, R; Micheletti, M I; Miele, G; Miller, W; Mollerach, S; Monasor, M; Monnier Ragaigne, D; Montanet, F; Morales, B; Morello, C; Moreno, J C; Morris, C; Mostafá, M; Muller, M A; Mussa, R; Navarra, G; Navarro, J L; Navas, S; Necesal, P; Nellen, L; Newman-Holmes, C; Newton, D; Nguyen Thi, T; Nierstenhoefer, N; Nitz, D; Nosek, D; Nozka, L; Oehlschläger, J; Ohnuki, T; Olinto, A; Olmos-Gilbaja, V M; Ortiz, M; Ortolani, F; Ostapchenko, S; Otero, L; Pacheco, N; Pakk Selmi-Dei, D; Palatka, M; Pallotta, J; Parente, G; Parizot, E; Parlati, S; Pastor, S; Patel, M; Paul, T; Pavlidou, V; Payet, K; Pech, M; Pekala, J; Pelayo, R; Pepe, I M; Perrone, L; Petrera, S; Petrinca, P; Petrov, Y; Pham Ngoc, Diep; Pham Ngoc, Dong; Pham Thi, T N; Pichel, A; Piegaia, R; Pierog, T; Pimenta, M; Pinto, T; Pirronello, V; Pisanti, O; Platino, M; Pochon, J; Privitera, P; Prouza, M; Quel, E J; Rautenberg, J; Redondo, A; Reucroft, S; Revenu, B; Rezende, F A S; Ridky, J; Riggi, S; Risse, M; Rivière, C; Rizi, V; Roberts, M; Robledo, C; Rodriguez, G; Rodríguez Frías, D; Rodriguez Martino, J; Rodriguez Rojo, J; Rodriguez-Cabo, I; Ros, G; Rosado, J; Roth, M; Rouillé-d'Orfeuil, B; Roulet, E; Rovero, A C; Salamida, F; Salazar, H; Salina, G; Sánchez, F; Santander, M; Santo, C E; Santos, E M; Sarazin, F; Sarkar, S; Sato, R; Scherini, V; Schieler, H; Schmidt, A; Schmidt, F; Schmidt, T; Scholten, O; Schovánek, P; Schüssler, F; Sciutto, S J; Scuderi, M; Segreto, A; Semikoz, D; Settimo, M; Shellard, R C; Sidelnik, I; Siffert, B B; Sigl, G; Smetniansky De Grande, N; Smiałkowski, A; Smída, R; Smith, A G K; Smith, B E; Snow, G R; Sokolsky, P; Sommers, P; Sorokin, J; Spinka, H; Squartini, R; Strazzeri, E; Stutz, A; Suarez, F; Suomijärvi, T; Supanitsky, A D; Sutherland, M S; Swain, J; Szadkowski, Z; Takahashi, J; Tamashiro, A; Tamburro, A; Taşcău, O; Tcaciuc, R; Thomas, D; Ticona, R; Tiffenberg, J; Timmermans, C; Tkaczyk, W; Todero Peixoto, C J; Tomé, B; Tonachini, A; Torres, I; Torresi, D; Travnicek, P; Tripathi, A; Tristram, G; Tscherniakhovski, D; Tueros, M; Tunnicliffe, V; Ulrich, R; Unger, M; Urban, M; Valdés Galicia, J F; Valiño, I; Valore, L; van den Berg, A M; van Elewyck, V; Vázquez, R A; Veberic, D; Veiga, A; Velarde, A; Venters, T; Verzi, V; Videla, M; Villaseñor, L; Vorobiov, S; Voyvodic, L; Wahlberg, H; Wainberg, O; Walker, P; Warner, D; Watson, A A; Westerhoff, S; Wieczorek, G; Wiencke, L; Wilczyńska, B; Wilczyński, H; Wileman, C; Winnick, M G; Wu, H; Wundheiler, B; Yamamoto, T; Younk, P; Zas, E; Zavrtanik, D; Zavrtanik, M; Zech, A; Zepeda, A; Ziolkowski, M

    2008-05-30

    The surface detector array of the Pierre Auger Observatory is sensitive to Earth-skimming tau neutrinos that interact in Earth's crust. Tau leptons from nu(tau) charged-current interactions can emerge and decay in the atmosphere to produce a nearly horizontal shower with a significant electromagnetic component. The data collected between 1 January 2004 and 31 August 2007 are used to place an upper limit on the diffuse flux of nu(tau) at EeV energies. Assuming an E(nu)(-2) differential energy spectrum the limit set at 90% C.L. is E(nu)(2)dN(nu)(tau)/dE(nu)<1.3 x 10(-7) GeV cm(-2) s(-1) sr(-1) in the energy range 2 x 10(17) eV< E(nu)< 2 x 10(19) eV.

  4. Skimming and Skipping Stones

    ERIC Educational Resources Information Center

    Humble, Steve

    2007-01-01

    This article presents an example of skimming and skipping stone motion in mathematical terms available to students studying A-level mathematics. The theory developed in the article postulates a possible mathematical model that is verified by experimental results.

  5. Ultra high-energy neutrino at GZK energy: Z-WW showering in dark halo and tau airshowers emerging from the Earth

    NASA Astrophysics Data System (ADS)

    Fargion, Daniele

    2003-02-01

    Relic neutrino nur light masses clustering in Galactic and Local Hot Dark Halos act as a beam dump calorimeter. Ultra High Energy nu, above ZeV, born by AGNs, GRBs at cosmic edges, overcoming the Greisen, Zatsepin, Kuzmin (GZK) cut-off, may hit near Z resonance and WW-ZZ channels energies: their showering into nucleons and gamma Ultra High Cosmic Ray (UHECR) fit observed data . Any tiny neutrino mass splitting may reflect into a twin bump at highest GZK energy cut-off. The lighter the neutrino masses the higher the Z-Showering cut-off. The Z or WW,ZZ showering might explain a peculiar clustering in observed UHECR spectra at 1019, 2x1019, 4x1019 eV found recently by AGASA. Coincidence of clustered UHECR with highest gamma BLac sources, originated either by neutral and charged particles (Q=0,+1,-1) is well tuned to Z-Showering Scenario. Additional prompt TeVs signals occur offering a natural solution of growing Infrared-TeV cut-off paradoxes related to distant TeV BLac sources and a GRB at TeV energy. Electromagnetic Cascades tail may explain correlation found between GeV-EGRET Sources and UHECR. Such UHE v Astrophysics might trace near GZK energy into Horizontal Tau Air-Showers originated by the UHE vτ Earth-Skimming in wide Corona Earth Crust around the observer; their consequent τ escape and decay upward in flight . These Upward and Horizontal τ Air-Showers UPTAUS, HORTAUS, monitor huge volumes from high mountains as well as observing from planes, balloons and satellites. HORTAUS from mountains observe corona masses at UHE v EeVs energies comparable to few km3, while from satellites at orbit altitudes, at GZK energies Enu>= 1019 eV, their corresponding Horizontal Corona Masses may even exceed 150 km3. The expected event rate may exceed a dozen of event a year in Z-WW Showering model from satellite.

  6. Tau physics

    SciTech Connect

    Perl, M.L.

    1993-03-01

    This report discusses the following topics: [tau] production and related [tau] properties; general discussion of [tau] decays; leptonic decays; hadronic decays; the [tau] in atomic physics; and the [tau] neutrino: [nu][sub [tau

  7. Tau physics

    SciTech Connect

    Perl, M.L.

    1993-03-01

    This report discusses the following topics: {tau} production and related {tau} properties; general discussion of {tau} decays; leptonic decays; hadronic decays; the {tau} in atomic physics; and the {tau} neutrino: {nu}{sub {tau}}

  8. Upper limit on the diffuse flux of UHE tau neutrinos from the Pierre Auger Observatory

    SciTech Connect

    Collaboration, The Pierre Auger

    2007-12-01

    The surface detector array of the Pierre Auger Observatory is sensitive to Earth-skimming tau-neutrinos {nu}{sub {tau}} that interact in the Earth's crust. Tau leptons from {tau}{sub {tau}} charged-current interactions can emerge and decay in the atmosphere to produce a nearly horizontal shower with a significant electromagnetic component. The data collected between 1 January 2004 and 31 August 2007 is used to place an upper limit on the diffuse flux of {nu}{sub {tau}} at EeV energies. Assuming an E{sub {nu}}{sup -2} differential energy spectrum the limit set at 90 % C.L. is E{sub {nu}}{sup 2} dN{sub {nu}{sub {tau}}}/dE{sub {nu}} < 1.3 x 10{sup -7} GeV cm{sup -2} s{sup -1} sr{sup -1} in the energy range 2 x 10{sup 17} eV < E{sub {nu}} < 2 x 10{sup 19} eV.

  9. Detection of tau neutrinos by imaging air Cherenkov telescopes

    NASA Astrophysics Data System (ADS)

    Góra, D.; Bernardini, E.

    2016-09-01

    This paper investigates the potential to detect tau neutrinos in the energy range of 1-1000 PeV searching for very inclined showers with imaging Cherenkov telescopes. A neutrino induced tau lepton escaping from the Earth may decay and initiate an air shower which can be detected by a fluorescence or Cherenkov telescope. We present here a study of the detection potential of Earth-skimming neutrinos taking into account neutrino interactions in the Earth crust, local matter distributions at various detector sites, the development of tau-induced showers in air and the detection of Cherenkov photons with IACTs. We analyzed simulated shower images on the camera focal plane and implemented generic reconstruction chains based on Hillas parameters. We find that present IACTs can distinguish air showers induced by tau neutrinos from the background of hadronic showers in the PeV-EeV energy range. We present the neutrino trigger efficiency obtained for a few configurations being considered for the next-generation Cherenkov telescopes, i.e. the Cherenkov Telescope Array. Finally, for a few representative neutrino spectra expected from astrophysical sources, we compare the expected event rates at running IACTs to what is expected for the dedicated IceCube neutrino telescope.

  10. Search for Point-like Sources of Ultra-high Energy Neutrinos at the Pierre Auger Observatory and Improved Limit on the Diffuse Flux of Tau Neutrinos

    NASA Astrophysics Data System (ADS)

    Pierre Auger Collaboration; Abreu, P.; Aglietta, M.; Ahlers, M.; Ahn, E. J.; Albuquerque, I. F. M.; Allard, D.; Allekotte, I.; Allen, J.; Allison, P.; Almela, A.; Alvarez Castillo, J.; Alvarez-Muñiz, J.; Alves Batista, R.; Ambrosio, M.; Aminaei, A.; Anchordoqui, L.; Andringa, S.; Antiči'c, T.; Aramo, C.; Arganda, E.; Arqueros, F.; Asorey, H.; Assis, P.; Aublin, J.; Ave, M.; Avenier, M.; Avila, G.; Badescu, A. M.; Balzer, M.; Barber, K. B.; Barbosa, A. F.; Bardenet, R.; Barroso, S. L. C.; Baughman, B.; Bäuml, J.; Baus, C.; Beatty, J. J.; Becker, K. H.; Bellétoile, A.; Bellido, J. A.; BenZvi, S.; Berat, C.; Bertou, X.; Biermann, P. L.; Billoir, P.; Blanch-Bigas, O.; Blanco, F.; Blanco, M.; Bleve, C.; Blümer, H.; Boháčová, M.; Boncioli, D.; Bonifazi, C.; Bonino, R.; Borodai, N.; Brack, J.; Brancus, I.; Brogueira, P.; Brown, W. C.; Bruijn, R.; Buchholz, P.; Bueno, A.; Buroker, L.; Burton, R. E.; Caballero-Mora, K. S.; Caccianiga, B.; Caramete, L.; Caruso, R.; Castellina, A.; Catalano, O.; Cataldi, G.; Cazon, L.; Cester, R.; Chauvin, J.; Cheng, S. H.; Chiavassa, A.; Chinellato, J. A.; Chirinos Diaz, J.; Chudoba, J.; Cilmo, M.; Clay, R. W.; Cocciolo, G.; Collica, L.; Coluccia, M. R.; Conceição, R.; Contreras, F.; Cook, H.; Cooper, M. J.; Coppens, J.; Cordier, A.; Coutu, S.; Covault, C. E.; Creusot, A.; Criss, A.; Cronin, J.; Curutiu, A.; Dagoret-Campagne, S.; Dallier, R.; Daniel, B.; Dasso, S.; Daumiller, K.; Dawson, B. R.; de Almeida, R. M.; De Domenico, M.; De Donato, C.; de Jong, S. J.; De La Vega, G.; de Mello Junior, W. J. M.; de Mello Neto, J. R. T.; De Mitri, I.; de Souza, V.; de Vries, K. D.; del Peral, L.; del Río, M.; Deligny, O.; Dembinski, H.; Dhital, N.; Di Giulio, C.; Díaz Castro, M. L.; Diep, P. N.; Diogo, F.; Dobrigkeit, C.; Docters, W.; D'Olivo, J. C.; Dong, P. N.; Dorofeev, A.; dos Anjos, J. C.; Dova, M. T.; D'Urso, D.; Dutan, I.; Ebr, J.; Engel, R.; Erdmann, M.; Escobar, C. O.; Espadanal, J.; Etchegoyen, A.; Facal San Luis, P.; Falcke, H.; Farrar, G.; Fauth, A. C.; Fazzini, N.; Ferguson, A. P.; Fick, B.; Figueira, J. M.; Filevich, A.; Filipčič, A.; Fliescher, S.; Fracchiolla, C. E.; Fraenkel, E. D.; Fratu, O.; Fröhlich, U.; Fuchs, B.; Gaior, R.; Gamarra, R. F.; Gambetta, S.; García, B.; Garcia Roca, S. T.; Garcia-Gamez, D.; Garcia-Pinto, D.; Gascon Bravo, A.; Gemmeke, H.; Ghia, P. L.; Giller, M.; Gitto, J.; Glass, H.; Gold, M. S.; Golup, G.; Gomez Albarracin, F.; Gómez Berisso, M.; Gómez Vitale, P. F.; Gonçalves, P.; Gonzalez, J. G.; Gookin, B.; Gorgi, A.; Gouffon, P.; Grashorn, E.; Grebe, S.; Griffith, N.; Grigat, M.; Grillo, A. F.; Guardincerri, Y.; Guarino, F.; Guedes, G. P.; Hansen, P.; Harari, D.; Harrison, T. A.; Harton, J. L.; Haungs, A.; Hebbeker, T.; Heck, D.; Herve, A. E.; Hojvat, C.; Hollon, N.; Holmes, V. C.; Homola, P.; Hörandel, J. R.; Horvath, P.; Hrabovský, M.; Huber, D.; Huege, T.; Insolia, A.; Ionita, F.; Italiano, A.; Jansen, S.; Jarne, C.; Jiraskova, S.; Josebachuili, M.; Kadija, K.; Kampert, K. H.; Karhan, P.; Kasper, P.; Katkov, I.; Kégl, B.; Keilhauer, B.; Keivani, A.; Kelley, J. L.; Kemp, E.; Kieckhafer, R. M.; Klages, H. O.; Kleifges, M.; Kleinfeller, J.; Knapp, J.; Koang, D.-H.; Kotera, K.; Krohm, N.; Krömer, O.; Kruppke-Hansen, D.; Kuempel, D.; Kulbartz, J. K.; Kunka, N.; La Rosa, G.; Lachaud, C.; LaHurd, D.; Latronico, L.; Lauer, R.; Lautridou, P.; Le Coz, S.; Leão, M. S. A. B.; Lebrun, D.; Lebrun, P.; Leigui de Oliveira, M. A.; Letessier-Selvon, A.; Lhenry-Yvon, I.; Link, K.; López, R.; Lopez Agüera, A.; Louedec, K.; Lozano Bahilo, J.; Lu, L.; Lucero, A.; Ludwig, M.; Lyberis, H.; Maccarone, M. C.; Macolino, C.; Maldera, S.; Maller, J.; Mandat, D.; Mantsch, P.; Mariazzi, A. G.; Marin, J.; Marin, V.; Maris, I. C.; Marquez Falcon, H. R.; Marsella, G.; Martello, D.; Martin, L.; Martinez, H.; Martínez Bravo, O.; Martraire, D.; Masías Meza, J. J.; Mathes, H. J.; Matthews, J.; Matthews, J. A. J.; Matthiae, G.; Maurel, D.; Maurizio, D.; Mazur, P. O.; Medina-Tanco, G.; Melissas, M.; Melo, D.; Menichetti, E.; Menshikov, A.; Mertsch, P.; Meurer, C.; Meyhandan, R.; Mi'canovi'c, S.; Micheletti, M. I.; Minaya, I. A.; Miramonti, L.; Molina-Bueno, L.; Mollerach, S.; Monasor, M.; Monnier Ragaigne, D.; Montanet, F.; Morales, B.; Morello, C.; Moreno, E.; Moreno, J. C.; Mostafá, M.; Moura, C. A.; Muller, M. A.; Müller, G.; Münchmeyer, M.; Mussa, R.; Navarra, G.; Navarro, J. L.; Navas, S.; Necesal, P.; Nellen, L.; Nelles, A.; Neuser, J.; Nhung, P. T.; Niechciol, M.; Niemietz, L.; Nierstenhoefer, N.; Nitz, D.; Nosek, D.; Nožka, L.; Oehlschläger, J.; Olinto, A.; Ortiz, M.; Pacheco, N.; Pakk Selmi-Dei, D.; Palatka, M.; Pallotta, J.; Palmieri, N.; Parente, G.; Parizot, E.; Parra, A.; Pastor, S.; Paul, T.; Pech, M.; Peķala, J.; Pelayo, R.; Pepe, I. M.; Perrone, L.; Pesce, R.; Petermann, E.; Petrera, S.; Petrolini, A.; Petrov, Y.; Pfendner, C.; Piegaia, R.; Pierog, T.; Pieroni, P.; Pimenta, M.; Pirronello, V.; Platino, M.; Plum, M.; Ponce, V. H.; Pontz, M.; Porcelli, A.; Privitera, P.; Prouza, M.; Quel, E. J.; Querchfeld, S.; Rautenberg, J.; Ravel, O.; Ravignani, D.; Revenu, B.; Ridky, J.; Riggi, S.; Risse, M.; Ristori, P.; Rivera, H.; Rizi, V.; Roberts, J.; Rodrigues de Carvalho, W.; Rodriguez, G.; Rodriguez Cabo, I.; Rodriguez Martino, J.; Rodriguez Rojo, J.; Rodríguez-Frías, M. D.; Ros, G.; Rosado, J.; Rossler, T.; Roth, M.; Rouillé-d'Orfeuil, B.; Roulet, E.; Rovero, A. C.; Rühle, C.; Saftoiu, A.; Salamida, F.; Salazar, H.; Salesa Greus, F.; Salina, G.; Sánchez, F.; Santo, C. E.; Santos, E.; Santos, E. M.; Sarazin, F.; Sarkar, B.; Sarkar, S.; Sato, R.; Scharf, N.; Scherini, V.; Schieler, H.; Schiffer, P.; Schmidt, A.; Scholten, O.; Schoorlemmer, H.; Schovancova, J.; Schovánek, P.; Schröder, F.; Schulte, S.; Schuster, D.; Sciutto, S. J.; Scuderi, M.; Segreto, A.; Settimo, M.; Shadkam, A.; Shellard, R. C.; Sidelnik, I.; Sigl, G.; Silva Lopez, H. H.; Sima, O.; 'Smiałkowski, A.; Šmída, R.; Snow, G. R.; Sommers, P.; Sorokin, J.; Spinka, H.; Squartini, R.; Srivastava, Y. N.; Stanic, S.; Stapleton, J.; Stasielak, J.; Stephan, M.; Stutz, A.; Suarez, F.; Suomijärvi, T.; Supanitsky, A. D.; Šuša, T.; Sutherland, M. S.; Swain, J.; Szadkowski, Z.; Szuba, M.; Tapia, A.; Tartare, M.; Taşcău, O.; Tcaciuc, R.; Thao, N. T.; Thomas, D.; Tiffenberg, J.; Timmermans, C.; Tkaczyk, W.; Todero Peixoto, C. J.; Toma, G.; Tomankova, L.; Tomé, B.; Tonachini, A.; Travnicek, P.; Tridapalli, D. B.; Tristram, G.; Trovato, E.; Tueros, M.; Ulrich, R.; Unger, M.; Urban, M.; Valdés Galicia, J. F.; Valiño, I.; Valore, L.; van Aar, G.; van den Berg, A. M.; van Vliet, A.; Varela, E.; Vargas Cárdenas, B.; Vázquez, J. R.; Vázquez, R. A.; Veberič, D.; Verzi, V.; Vicha, J.; Videla, M.; Villaseñor, L.; Wahlberg, H.; Wahrlich, P.; Wainberg, O.; Walz, D.; Watson, A. A.; Weber, M.; Weidenhaupt, K.; Weindl, A.; Werner, F.; Westerhoff, S.; Whelan, B. J.; Widom, A.; Wieczorek, G.; Wiencke, L.; Wilczyńska, B.; Wilczyński, H.; Will, M.; Williams, C.; Winchen, T.; Wommer, M.; Wundheiler, B.; Yamamoto, T.; Yapici, T.; Younk, P.; Yuan, G.; Yushkov, A.; Zamorano Garcia, B.; Zas, E.; Zavrtanik, D.; Zavrtanik, M.; Zaw, I.; Zepeda, A.; Zhou, J.; Zhu, Y.; Zimbres Silva, M.; Ziolkowski, M.

    2012-08-01

    The surface detector array of the Pierre Auger Observatory can detect neutrinos with energy E ν between 1017 eV and 1020 eV from point-like sources across the sky south of +55° and north of -65° declinations. A search has been performed for highly inclined extensive air showers produced by the interaction of neutrinos of all flavors in the atmosphere (downward-going neutrinos), and by the decay of tau leptons originating from tau neutrino interactions in Earth's crust (Earth-skimming neutrinos). No candidate neutrinos have been found in data up to 2010 May 31. This corresponds to an equivalent exposure of ~3.5 years of a full surface detector array for the Earth-skimming channel and ~2 years for the downward-going channel. An improved upper limit on the diffuse flux of tau neutrinos has been derived. Upper limits on the neutrino flux from point-like sources have been derived as a function of the source declination. Assuming a differential neutrino flux k PS · E -2 ν from a point-like source, 90% confidence level upper limits for k PS at the level of ≈5 × 10-7 and 2.5 × 10-6 GeV cm-2 s-1 have been obtained over a broad range of declinations from the searches for Earth-skimming and downward-going neutrinos, respectively.

  11. Tau Now

    NASA Astrophysics Data System (ADS)

    Fargion, D.; Oliva, P.

    2016-10-01

    :arXiv:astro-ph/9906450], as well as up-going tau air showers escaping our Earth, observable in air by their fluorescence lights as in AUGER and TA, might be a signal at EeVs energies. At lower energies blazing few PeVs tau airshower flashes are better observable from the top of the mountains, by an array located in a crown edge (as water Cherenkov, telescope Cherenkov or radio array), as it has been done in ASHRA or it might be done on ideal modified GRAND experiments constructed within aeolian towers by radio array possibly in mountains, facing the wide peculiar τ neutrino sky: our own Earth.

  12. Tau physics and tau factories

    SciTech Connect

    Perl, M.L.

    1989-01-01

    Substantial progress in tau lepton physics requires larger and cleaner samples of /tau/'s produced in e/sup +/e/sup minus/ ..-->.. /tau//sup +//tau//sup minus/. Single-tagging of the /tau/ pair is crucial. Possibilities for such progress at particle factories are discussed with emphasis on the Tau-Charm Factory concept. 30 refs., 1 fig., 1 tab.

  13. Upper Limit on the Diffuse Flux of Ultrahigh Energy Tau Neutrinos from the Pierre Auger Observatory

    NASA Astrophysics Data System (ADS)

    Abraham, J.; Abreu, P.; Aglietta, M.; Aguirre, C.; Allard, D.; Allekotte, I.; Allen, J.; Allison, P.; Alvarez-Muñiz, J.; Ambrosio, M.; Anchordoqui, L.; Andringa, S.; Anzalone, A.; Aramo, C.; Argirò, S.; Arisaka, K.; Armengaud, E.; Arneodo, F.; Arqueros, F.; Asch, T.; Asorey, H.; Assis, P.; Atulugama, B. S.; Aublin, J.; Ave, M.; Avila, G.; Bäcker, T.; Badagnani, D.; Barbosa, A. F.; Barnhill, D.; Barroso, S. L. C.; Bauleo, P.; Beatty, J. J.; Beau, T.; Becker, B. R.; Becker, K. H.; Bellido, J. A.; Benzvi, S.; Berat, C.; Bergmann, T.; Bernardini, P.; Bertou, X.; Biermann, P. L.; Billoir, P.; Blanch-Bigas, O.; Blanco, F.; Blasi, P.; Bleve, C.; Blümer, H.; Boháčová, M.; Bonifazi, C.; Bonino, R.; Boratav, M.; Brack, J.; Brogueira, P.; Brown, W. C.; Buchholz, P.; Bueno, A.; Burton, R. E.; Busca, N. G.; Caballero-Mora, K. S.; Cai, B.; Camin, D. V.; Caramete, L.; Caruso, R.; Carvalho, W.; Castellina, A.; Catalano, O.; Cataldi, G.; Cazon, L.; Cester, R.; Chauvin, J.; Chiavassa, A.; Chinellato, J. A.; Chou, A.; Chye, J.; Clark, P. D. J.; Clay, R. W.; Colombo, E.; Conceição, R.; Connolly, B.; Contreras, F.; Coppens, J.; Cordier, A.; Cotti, U.; Coutu, S.; Covault, C. E.; Creusot, A.; Criss, A.; Cronin, J.; Curutiu, A.; Dagoret-Campagne, S.; Daumiller, K.; Dawson, B. R.; de Almeida, R. M.; de Donato, C.; de Jong, S. J.; de La Vega, G.; de Mello Junior, W. J. M.; de Mello Neto, J. R. T.; Demitri, I.; de Souza, V.; Del Peral, L.; Deligny, O.; Della Selva, A.; Delle Fratte, C.; Dembinski, H.; di Giulio, C.; Diaz, J. C.; Dobrigkeit, C.; D'Olivo, J. C.; Dornic, D.; Dorofeev, A.; Dos Anjos, J. C.; Dova, M. T.; D'Urso, D.; Dutan, I.; Duvernois, M. A.; Engel, R.; Epele, L.; Erdmann, M.; Escobar, C. O.; Etchegoyen, A.; Facal San Luis, P.; Falcke, H.; Farrar, G.; Fauth, A. C.; Fazzini, N.; Ferrer, F.; Ferry, S.; Fick, B.; Filevich, A.; Filipčič, A.; Fleck, I.; Fonte, R.; Fracchiolla, C. E.; Fulgione, W.; García, B.; García Gámez, D.; Garcia-Pinto, D.; Garrido, X.; Geenen, H.; Gelmini, G.; Gemmeke, H.; Ghia, P. L.; Giller, M.; Glass, H.; Gold, M. S.; Golup, G.; Gomez Albarracin, F.; Gómez Berisso, M.; Gómez Herrero, R.; Gonçalves, P.; Gonçalves Do Amaral, M.; Gonzalez, D.; Gonzalez, J. G.; González, M.; Góra, D.; Gorgi, A.; Gouffon, P.; Grassi, V.; Grillo, A. F.; Grunfeld, C.; Guardincerri, Y.; Guarino, F.; Guedes, G. P.; Gutiérrez, J.; Hague, J. D.; Hamilton, J. C.; Hansen, P.; Harari, D.; Harmsma, S.; Harton, J. L.; Haungs, A.; Hauschildt, T.; Healy, M. D.; Hebbeker, T.; Hebrero, G.; Heck, D.; Hojvat, C.; Holmes, V. C.; Homola, P.; Hörandel, J.; Horneffer, A.; Horvat, M.; Hrabovský, M.; Huege, T.; Hussain, M.; Iarlori, M.; Insolia, A.; Ionita, F.; Italiano, A.; Kaducak, M.; Kampert, K. H.; Karova, T.; Kégl, B.; Keilhauer, B.; Kemp, E.; Kieckhafer, R. M.; Klages, H. O.; Kleifges, M.; Kleinfeller, J.; Knapik, R.; Knapp, J.; Koang, D.-H.; Krieger, A.; Krömer, O.; Kuempel, D.; Kunka, N.; Kusenko, A.; La Rosa, G.; Lachaud, C.; Lago, B. L.; Lebrun, D.; Lebrun, P.; Lee, J.; Leigui de Oliveira, M. A.; Letessier-Selvon, A.; Leuthold, M.; Lhenry-Yvon, I.; López, R.; Lopez Agüera, A.; Lozano Bahilo, J.; Luna García, R.; Maccarone, M. C.; Macolino, C.; Maldera, S.; Mancarella, G.; Manceñido, M. E.; Mandat, D.; Mantsch, P.; Mariazzi, A. G.; Maris, I. C.; Marquez Falcon, H. R.; Martello, D.; Martínez, J.; Martínez Bravo, O.; Mathes, H. J.; Matthews, J.; Matthews, J. A. J.; Matthiae, G.; Maurizio, D.; Mazur, P. O.; McCauley, T.; McEwen, M.; McNeil, R. R.; Medina, M. C.; Medina-Tanco, G.; Meli, A.; Melo, D.; Menichetti, E.; Menschikov, A.; Meurer, Chr.; Meyhandan, R.; Micheletti, M. I.; Miele, G.; Miller, W.; Mollerach, S.; Monasor, M.; Monnier Ragaigne, D.; Montanet, F.; Morales, B.; Morello, C.; Moreno, J. C.; Morris, C.; Mostafá, M.; Muller, M. A.; Mussa, R.; Navarra, G.; Navarro, J. L.; Navas, S.; Necesal, P.; Nellen, L.; Newman-Holmes, C.; Newton, D.; Nguyen Thi, T.; Nierstenhoefer, N.; Nitz, D.; Nosek, D.; Nožka, L.; Oehlschläger, J.; Ohnuki, T.; Olinto, A.; Olmos-Gilbaja, V. M.; Ortiz, M.; Ortolani, F.; Ostapchenko, S.; Otero, L.; Pacheco, N.; Pakk Selmi-Dei, D.; Palatka, M.; Pallotta, J.; Parente, G.; Parizot, E.; Parlati, S.; Pastor, S.; Patel, M.; Paul, T.; Pavlidou, V.; Payet, K.; Pech, M.; Pękala, J.; Pelayo, R.; Pepe, I. M.; Perrone, L.; Petrera, S.; Petrinca, P.; Petrov, Y.; Pham Ngoc, Diep; Pham Ngoc, Dong; Pham Thi, T. N.; Pichel, A.; Piegaia, R.; Pierog, T.; Pimenta, M.; Pinto, T.; Pirronello, V.; Pisanti, O.; Platino, M.; Pochon, J.; Privitera, P.; Prouza, M.; Quel, E. J.; Rautenberg, J.; Redondo, A.; Reucroft, S.; Revenu, B.; Rezende, F. A. S.; Ridky, J.; Riggi, S.; Risse, M.; Rivière, C.; Rizi, V.; Roberts, M.; Robledo, C.; Rodriguez, G.; Rodríguez Frías, D.; Rodriguez Martino, J.; Rodriguez Rojo, J.; Rodriguez-Cabo, I.; Ros, G.; Rosado, J.; Roth, M.; Rouillé-D'Orfeuil, B.; Roulet, E.; Rovero, A. C.; Salamida, F.; Salazar, H.; Salina, G.; Sánchez, F.; Santander, M.; Santo, C. E.; Santos, E. M.; Sarazin, F.; Sarkar, S.; Sato, R.; Scherini, V.; Schieler, H.; Schmidt, A.; Schmidt, F.; Schmidt, T.; Scholten, O.; Schovánek, P.; Schüssler, F.; Sciutto, S. J.; Scuderi, M.; Segreto, A.; Semikoz, D.; Settimo, M.; Shellard, R. C.; Sidelnik, I.; Siffert, B. B.; Sigl, G.; Smetniansky de Grande, N.; Smiałkowski, A.; Šmída, R.; Smith, A. G. K.; Smith, B. E.; Snow, G. R.; Sokolsky, P.; Sommers, P.; Sorokin, J.; Spinka, H.; Squartini, R.; Strazzeri, E.; Stutz, A.; Suarez, F.; Suomijärvi, T.; Supanitsky, A. D.; Sutherland, M. S.; Swain, J.; Szadkowski, Z.; Takahashi, J.; Tamashiro, A.; Tamburro, A.; Taşcău, O.; Tcaciuc, R.; Thomas, D.; Ticona, R.; Tiffenberg, J.; Timmermans, C.; Tkaczyk, W.; Todero Peixoto, C. J.; Tomé, B.; Tonachini, A.; Torres, I.; Torresi, D.; Travnicek, P.; Tripathi, A.; Tristram, G.; Tscherniakhovski, D.; Tueros, M.; Tunnicliffe, V.; Ulrich, R.; Unger, M.; Urban, M.; Valdés Galicia, J. F.; Valiño, I.; Valore, L.; van den Berg, A. M.; van Elewyck, V.; Vázquez, R. A.; Veberič, D.; Veiga, A.; Velarde, A.; Venters, T.; Verzi, V.; Videla, M.; Villaseñor, L.; Vorobiov, S.; Voyvodic, L.; Wahlberg, H.; Wainberg, O.; Walker, P.; Warner, D.; Watson, A. A.; Westerhoff, S.; Wieczorek, G.; Wiencke, L.; Wilczyńska, B.; Wilczyński, H.; Wileman, C.; Winnick, M. G.; Wu, H.; Wundheiler, B.; Yamamoto, T.; Younk, P.; Zas, E.; Zavrtanik, D.; Zavrtanik, M.; Zech, A.; Zepeda, A.; Ziolkowski, M.

    2008-05-01

    The surface detector array of the Pierre Auger Observatory is sensitive to Earth-skimming tau neutrinos that interact in Earth’s crust. Tau leptons from ντ charged-current interactions can emerge and decay in the atmosphere to produce a nearly horizontal shower with a significant electromagnetic component. The data collected between 1 January 2004 and 31 August 2007 are used to place an upper limit on the diffuse flux of ντ at EeV energies. Assuming an Eν-2 differential energy spectrum the limit set at 90% C.L. is Eν2dNντ/dEν<1.3×10-7GeVcm-2s-1sr-1 in the energy range 2×1017eV

  14. SEARCH FOR POINT-LIKE SOURCES OF ULTRA-HIGH ENERGY NEUTRINOS AT THE PIERRE AUGER OBSERVATORY AND IMPROVED LIMIT ON THE DIFFUSE FLUX OF TAU NEUTRINOS

    SciTech Connect

    Abreu, P.; Andringa, S.; Aglietta, M.; Ahlers, M.; Ahn, E. J.; Albuquerque, I. F. M.; Allard, D.; Allekotte, I.; Allen, J.; Allison, P.; Almela, A.; Alvarez Castillo, J.; Alvarez-Muniz, J.; Alves Batista, R.; Ambrosio, M.; Aramo, C.; Aminaei, A.; Anchordoqui, L.; Antici'c, T.; Collaboration: Pierre Auger Collaboration; and others

    2012-08-10

    The surface detector array of the Pierre Auger Observatory can detect neutrinos with energy E{sub {nu}} between 10{sup 17} eV and 10{sup 20} eV from point-like sources across the sky south of +55 Degree-Sign and north of -65 Degree-Sign declinations. A search has been performed for highly inclined extensive air showers produced by the interaction of neutrinos of all flavors in the atmosphere (downward-going neutrinos), and by the decay of tau leptons originating from tau neutrino interactions in Earth's crust (Earth-skimming neutrinos). No candidate neutrinos have been found in data up to 2010 May 31. This corresponds to an equivalent exposure of {approx}3.5 years of a full surface detector array for the Earth-skimming channel and {approx}2 years for the downward-going channel. An improved upper limit on the diffuse flux of tau neutrinos has been derived. Upper limits on the neutrino flux from point-like sources have been derived as a function of the source declination. Assuming a differential neutrino flux k{sub PS} {center_dot} E {sup -2}{sub {nu}} from a point-like source, 90% confidence level upper limits for k{sub PS} at the level of Almost-Equal-To 5 Multiplication-Sign 10{sup -7} and 2.5 Multiplication-Sign 10{sup -6} GeV cm{sup -2} s{sup -1} have been obtained over a broad range of declinations from the searches for Earth-skimming and downward-going neutrinos, respectively.

  15. 7 CFR 58.233 - Skim milk.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Skim milk. 58.233 Section 58.233 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... Materials § 58.233 Skim milk. The skim milk shall be separated from whole milk meeting the requirements...

  16. 7 CFR 58.233 - Skim milk.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 3 2013-01-01 2013-01-01 false Skim milk. 58.233 Section 58.233 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... Materials § 58.233 Skim milk. The skim milk shall be separated from whole milk meeting the requirements as...

  17. 7 CFR 58.233 - Skim milk.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 3 2012-01-01 2012-01-01 false Skim milk. 58.233 Section 58.233 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... Materials § 58.233 Skim milk. The skim milk shall be separated from whole milk meeting the requirements as...

  18. 7 CFR 58.233 - Skim milk.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 3 2014-01-01 2014-01-01 false Skim milk. 58.233 Section 58.233 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... Materials § 58.233 Skim milk. The skim milk shall be separated from whole milk meeting the requirements as...

  19. 7 CFR 58.233 - Skim milk.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 3 2011-01-01 2011-01-01 false Skim milk. 58.233 Section 58.233 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... Materials § 58.233 Skim milk. The skim milk shall be separated from whole milk meeting the requirements...

  20. Tau Structures

    PubMed Central

    Avila, Jesus; Jiménez, Juan S.; Sayas, Carmen L.; Bolós, Marta; Zabala, Juan C.; Rivas, Germán; Hernández, Felix

    2016-01-01

    Tau is a microtubule-associated protein that plays an important role in axonal stabilization, neuronal development, and neuronal polarity. In this review, we focus on the primary, secondary, tertiary, and quaternary tau structures. We describe the structure of tau from its specific residues until its conformation in dimers, oligomers, and larger polymers in physiological and pathological situations. PMID:27877124

  1. TAG Based Skimming In ATLAS

    NASA Astrophysics Data System (ADS)

    Doherty, T.; Cranshaw, J.; Hrivnac, J.; Slater, M.; Nowak, M.; Quilty, D.; Zhang, Q.

    2012-12-01

    The ATLAS detector at the LHC takes data at 200-500 Hz for several months per year accumulating billions of events for hundreds of physics analyses. TAGs are event-level metadata allowing a quick search for interesting events based on selection criteria defined by the user. They are stored in a file-based format as well as in relational databases. The overall TAG system architecture encompasses a range of interconnected services that provide functionality for the required use cases such as event selection, display, extraction and skimming. Skimming can be used to navigate to any of the pre-TAG data products. The services described in this paper address use cases that range in scale from selecting a handful of interesting events for an analysis specific study to creating physics working group samples on the ATLAS production system. This paper will focus on the workflow aspects involved in creating pre and post TAG data products from a TAG selection using the Grid in the context of the overall TAG system architecture. The emphasis will be on the range of demands that the implemented use cases place on these workflows and on the infrastructure. The tradeoffs of various workflow strategies will be discussed including scalability issues and other concerns that occur when integrating with data management and production systems.

  2. Search for Pev-Eev Tau Neutrinos and Optical Transients from Violent Objects with ASHRA-1

    NASA Astrophysics Data System (ADS)

    Sasaki, Makoto

    2014-06-01

    Ashra is a project to build an unconventional optical telescope complex that images a very wide field of view (FOV), covering 77% of the sky, yet with the angle resolution of a few arcmin, with the use of image intensifier and CMOS technology. The project primarily aims to observe Cherenkov and fluorescence light from air-shower developments. It can also be used to monitor optical transients in the wide FOV. The detector has great sensitivity in the PeV-EeV region using the Earth-skimming (ES) tau neutrino technique, and can be used to search for neutrinos originating from hadron acceleration in astronomical objects. Additional advantages are perfect shielding of cosmic ray secondaries, precision determination of arrival direction, and negligible atmospheric neutrino background. Ashra-1 completes its 3rd observation period, the first dedicated to taking physics data for PeV-EeV tau neutrinos with the best instantaneous sensitivity and optical transients, in March 2013. From January 2012 until end of March 2013, about 1950 hours of data have been taken out of 2006 hours possible due to light constraints. For optical transients, we have 3763 additional hours of data taken from 2008 until 2011. Ashra-1 has well demonstrated search for PeV-EeV tau neutrinos and optical flashes from a specific violent object in multi time domains with good pointing accuracy.

  3. 21 CFR 133.189 - Skim milk cheese for manufacturing.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Skim milk cheese for manufacturing. 133.189... Standardized Cheese and Related Products § 133.189 Skim milk cheese for manufacturing. (a) Skim milk cheese for manufacturing is the food prepared from skim milk and other ingredients specified in this section, by...

  4. 21 CFR 133.189 - Skim milk cheese for manufacturing.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Skim milk cheese for manufacturing. 133.189... Standardized Cheese and Related Products § 133.189 Skim milk cheese for manufacturing. (a) Skim milk cheese for manufacturing is the food prepared from skim milk and other ingredients specified in this section, by...

  5. 21 CFR 133.189 - Skim milk cheese for manufacturing.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Skim milk cheese for manufacturing. 133.189... Standardized Cheese and Related Products § 133.189 Skim milk cheese for manufacturing. (a) Skim milk cheese for manufacturing is the food prepared from skim milk and other ingredients specified in this section, by...

  6. 21 CFR 133.189 - Skim milk cheese for manufacturing.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Skim milk cheese for manufacturing. 133.189... Standardized Cheese and Related Products § 133.189 Skim milk cheese for manufacturing. (a) Skim milk cheese for manufacturing is the food prepared from skim milk and other ingredients specified in this section, by...

  7. 21 CFR 133.189 - Skim milk cheese for manufacturing.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Skim milk cheese for manufacturing. 133.189... Standardized Cheese and Related Products § 133.189 Skim milk cheese for manufacturing. (a) Skim milk cheese for manufacturing is the food prepared from skim milk and other ingredients specified in this section, by the...

  8. 21 CFR 133.191 - Part-skim spiced cheeses.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Part-skim spiced cheeses. 133.191 Section 133.191... FOR HUMAN CONSUMPTION CHEESES AND RELATED CHEESE PRODUCTS Requirements for Specific Standardized Cheese and Related Products § 133.191 Part-skim spiced cheeses. Part-skim spiced cheeses conform to the...

  9. 21 CFR 133.191 - Part-skim spiced cheeses.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Part-skim spiced cheeses. 133.191 Section 133.191... FOR HUMAN CONSUMPTION CHEESES AND RELATED CHEESE PRODUCTS Requirements for Specific Standardized Cheese and Related Products § 133.191 Part-skim spiced cheeses. Part-skim spiced cheeses conform to the...

  10. Document Skimming Support Environment for Surveying Documents in Creative Activities

    NASA Astrophysics Data System (ADS)

    Hayama, Tessai; Kanai, Takashi; Kunifuji, Susumu

    This paper proposes a document skimming environment for surveying documents in our research. Although there are a lot of on-line documents on our surroundings, people, generally, prefer printing out on-line research papers from computer screen. For this reason, although skimming is used for reading documents in our daily life, it is difficult for us to skim documents from computer screens. Therefore, we developed a document skimming environment. The environment has a skimming support system and a recommendation system. The skimming support system supports skimming documents from computer screens by the interface, which is applied the Fisheye effect and the Overview+detail effect. Focus points of the Fisheye effect are the sentences selected by the original sentence extraction algorithm based on the value of standard distribution, and the Overview interface is displayed automatically the generated table of contents. The recommendation system generates personalized summaries by the collaborate filtering, which use users' log of the skimming support system. Furthermore, evaluation results show as follows; The value of F-measure of our sentence extraction algorithm is higher than it of the sentence extraction algorithm based on TF or Japanese lexical chaining method, the skimming support system is more effective method to skim documents from computer screen than paper, and the skimming support environment is more effective method to product research proposal documents than paper.

  11. The Tau Code

    PubMed Central

    Avila, Jesús

    2009-01-01

    In this short review, I will focus on how a unique tau gene may produce many tau isoforms through alternative splicing and how the phosphorylation of these isoforms by different kinases may affect their activity and behaviour. Indeed, each of the different tau isoforms may play a distinct role under both physiological and pathological conditions. Thus, I will discuss whether a tau code exists that might explain the involvement of different tau isoforms in different cellular functions. PMID:20552052

  12. What Renders TAU Toxic

    PubMed Central

    Götz, Jürgen; Xia, Di; Leinenga, Gerhard; Chew, Yee Lian; Nicholas, Hannah R.

    2013-01-01

    TAU is a microtubule-associated protein that under pathological conditions such as Alzheimer’s disease (AD) forms insoluble, filamentous aggregates. When 20 years after TAU’s discovery the first TAU transgenic mouse models were established, one declared goal that was achieved was the modeling of authentic TAU aggregate formation in the form of neurofibrillary tangles. However, as we review here, it has become increasingly clear that TAU causes damage much before these filamentous aggregates develop. In fact, because TAU is a scaffolding protein, increased levels and an altered subcellular localization (due to an increased insolubility and impaired clearance) result in the interaction of TAU with cellular proteins with which it would otherwise either not interact or do so to a lesser degree, thereby impairing their physiological functions. We specifically discuss the non-axonal localization of TAU, the role phosphorylation has in TAU toxicity and how TAU impairs mitochondrial functions. A major emphasis is on what we have learned from the four available TAU knock-out models in mice, and the knock-out of the TAU/MAP2 homolog PTL-1 in worms. It has been proposed that in human pathological conditions such as AD, a rare toxic TAU species exists which needs to be specifically removed to abrogate TAU’s toxicity and restore neuronal functions. However, what is toxic in one context may not be in another, and simply reducing, but not fully abolishing TAU levels may be sufficient to abrogate TAU toxicity. PMID:23772223

  13. UX Tau A

    NASA Technical Reports Server (NTRS)

    2007-01-01

    This is an artist's rendition of the one-million-year-old star system called UX Tau A, located approximately 450 light-years away. Observations from NASA's Spitzer Space Telescope showed a gap in the dusty planet-forming disk swirling around the system's central sun-like star.

    Spitzer saw a gap in UX Tau A's disk that extends from 0.2 to 56 astronomical units (an astronomical unit is the distance between the sun and Earth). The gap extends from the equivalent of Mercury to Pluto in our solar system, and is sandwiched between thick inner and outer disks on either side. Astronomers suspect that the gap was carved out by one or more forming planets.

    Such dusty disks are where planets are thought to be born. Dust grains clump together like snowballs to form larger rocks, and then the bigger rocks collide to form the cores of planets. When rocks revolve around their central star, they act like cosmic vacuum cleaners, picking up all the gas and dust in their path and creating gaps.

    Although gaps have been detected in disks swirling around young stars before, UX Tau A is special because the gap is sandwiched between two thick disks of dust. An inner thick dusty disk hugs the central star, then, moving outward, there is a gap, followed by another thick doughnut-shaped disk. Other systems with gaps contain very little to no dust near the central star. In other words, those gaps are more like big holes in the centers of disks.

    Some scientists suspect that these holes could have been carved out by a process called photoevaporation. Photoevaporation occurs when radiation from the central star heats up the gas and dust around it to the point where it evaporates away. The fact that there is thick disk swirling extremely close to UX Tau A's central star rules out the photoevaporation scenario. If photoevaporation from the star played a role, then large amounts of dust would not be floating so close to the star.

  14. [Phosphorylation of tau protein].

    PubMed

    Uchida, T; Ishiguro, K

    1990-05-01

    In aged human brain and particularly in Alzheimer's disease brain, paired helical filaments (PHFs) accumulate in the neuronal cell. Recently, it has been found that the highly phosphorylated tau protein, one of the microtubule-associated proteins (MAPs), is a component of PHF. The authors attempted to clarify the mechanism underlying the accumulation of PHF from the following two aspects; 1) What is the mechanism of phosphorylation of tau protein? 2) Is the highly phosphorylated tau protein capable of forming PHFs? From rat or bovine microtubule proteins we partially purified and characterized a novel protein kinase that specifically phosphorylated tau and MAP2 among many proteins in the brain extract, and which formed a PHF epitope on the phosphorylated human tau. This enzyme was one of the protein serine/threonine kinases and was independent of known second messengers. The phosphorylation of tau by this enzyme was stimulated by tubulin under the condition of microtubule formation, suggesting that the phosphorylation of tau could occur concomitantly with microtubule formation in the brain. Since this kinase was usually bound to tau but not directly to tubulin, the enzyme was associated with microtubules through tau. From these properties related to tau, this kinase is designated as tau protein kinase. The tau that been phosphorylated with this kinase using [gamma-32P]ATP as a phosphate donor, was digested by endoprotinase Lys-C to produce three labeled fragments, K1, K2 and K3. These three fragments were sequenced and the phosphorylation sites on tau by this kinase were identified. The K2 fragment overlapped with the tau-1 site known to be one of the phosphorylation site in PHF. This result strengthens the possibility that tau protein phosphorylated by tau protein kinase is incorporated into PHF. Tubulin binding sites on tau were located between K1 and K3 fragments, while K2 fragment was located in the neighboring to N-terminus of K1. No phosphorylated sites were

  15. 21 CFR 163.140 - Skim milk chocolate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Skim milk chocolate. 163.140 Section 163.140 Food... milk chocolate. (a) Description. Skim milk chocolate is the food that conforms to the standard of identity, and is subject to the requirements for label declaration of ingredients for milk chocolate in...

  16. Preservation of Malassezia pachydermatis using skimmed milk as cryoprotective agent.

    PubMed

    Silva Sergent, F A; Acosta-Hernández, B; Raduán Jaber, J; Rosario Medina, I; Ferrer Quintana, O; Real Valcárcel, F; Padilla Castillo, D; Déniz Suárez, S

    2017-01-01

    This study evaluated the effect of skimmed milk as a cryoprotectant for the maintenance and long-term preservation of 70 Malassezia pachydermatis strains. An initial suspension of each strain was prepared in sterile distilled water with skimmed milk. The most effective method was cryopreservation that ensured 100% viability for 2years. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. 21 CFR 163.140 - Skim milk chocolate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Skim milk chocolate. 163.140 Section 163.140 Food... milk chocolate. (a) Description. Skim milk chocolate is the food that conforms to the standard of identity, and is subject to the requirements for label declaration of ingredients for milk chocolate in...

  18. 21 CFR 163.140 - Skim milk chocolate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Skim milk chocolate. 163.140 Section 163.140 Food... milk chocolate. (a) Description. Skim milk chocolate is the food that conforms to the standard of identity, and is subject to the requirements for label declaration of ingredients for milk chocolate in...

  19. 21 CFR 163.140 - Skim milk chocolate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Skim milk chocolate. 163.140 Section 163.140 Food... milk chocolate. (a) Description. Skim milk chocolate is the food that conforms to the standard of identity, and is subject to the requirements for label declaration of ingredients for milk chocolate in...

  20. 21 CFR 163.140 - Skim milk chocolate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Skim milk chocolate. 163.140 Section 163.140 Food... milk chocolate. (a) Description. Skim milk chocolate is the food that conforms to the standard of identity, and is subject to the requirements for label declaration of ingredients for milk chocolate...

  1. 21 CFR 133.158 - Low-moisture part-skim mozzarella and scamorza cheese.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Low-moisture part-skim mozzarella and scamorza... for Specific Standardized Cheese and Related Products § 133.158 Low-moisture part-skim mozzarella and scamorza cheese. Low-moisture part-skim mozzarella cheese and low-moisture part-skim scamorza...

  2. 21 CFR 133.158 - Low-moisture part-skim mozzarella and scamorza cheese.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Low-moisture part-skim mozzarella and scamorza... for Specific Standardized Cheese and Related Products § 133.158 Low-moisture part-skim mozzarella and scamorza cheese. Low-moisture part-skim mozzarella cheese and low-moisture part-skim scamorza...

  3. 21 CFR 133.158 - Low-moisture part-skim mozzarella and scamorza cheese.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Low-moisture part-skim mozzarella and scamorza... for Specific Standardized Cheese and Related Products § 133.158 Low-moisture part-skim mozzarella and scamorza cheese. Low-moisture part-skim mozzarella cheese and low-moisture part-skim scamorza...

  4. Propagation of Tau aggregates.

    PubMed

    Goedert, Michel; Spillantini, Maria Grazia

    2017-05-30

    Since 2009, evidence has accumulated to suggest that Tau aggregates form first in a small number of brain cells, from where they propagate to other regions, resulting in neurodegeneration and disease. Propagation of Tau aggregates is often called prion-like, which refers to the capacity of an assembled protein to induce the same abnormal conformation in a protein of the same kind, initiating a self-amplifying cascade. In addition, prion-like encompasses the release of protein aggregates from brain cells and their uptake by neighbouring cells. In mice, the intracerebral injection of Tau inclusions induced the ordered assembly of monomeric Tau, followed by its spreading to distant brain regions. Short fibrils constituted the major species of seed-competent Tau. The existence of several human Tauopathies with distinct fibril morphologies has led to the suggestion that different molecular conformers (or strains) of aggregated Tau exist.

  5. Amyloidogenesis of Tau protein.

    PubMed

    Nizynski, Bartosz; Dzwolak, Wojciech; Nieznanski, Krzysztof

    2017-08-17

    The role of microtubule-associated protein Tau in neurodegeneration has been extensively investigated since the discovery of Tau amyloid aggregates in the brains of patients with Alzheimer's disease (AD). The process of formation of amyloid fibrils is known as amyloidogenesis and attracts much attention as a potential target in the prevention and treatment of neurodegenerative conditions linked to protein aggregation. Cerebral deposition of amyloid aggregates of Tau is observed not only in AD but also in numerous other tauopathies and prion diseases. Amyloidogenesis of intrinsically unstructured monomers of Tau can be triggered by mutations in the Tau gene, post-translational modifications, or interactions with polyanionic molecules and aggregation-prone proteins/peptides. The self-assembly of amyloid fibrils of Tau shares a number of characteristic features with amyloidogenesis of other proteins involved in neurodegenerative diseases. For example, in vitro experiments have demonstrated that the nucleation phase, which is the rate-limiting stage of Tau amyloidogenesis, is shortened in the presence of fragmented preformed Tau fibrils acting as aggregation templates ("seeds"). Accordingly, Tau aggregates released by tauopathy-affected neurons can spread the neurodegenerative process in the brain through a prion-like mechanism, originally described for the pathogenic form of prion protein. Moreover, Tau has been shown to form amyloid strains-structurally diverse self-propagating aggregates of potentially various pathological effects, resembling in this respect prion strains. Here, we review the current literature on Tau aggregation and discuss mechanisms of propagation of Tau amyloid in the light of the prion-like paradigm. © 2017 The Protein Society.

  6. Limit on the diffuse flux of ultrahigh energy tau neutrinos with the surface detector of the Pierre Auger Observatory

    NASA Astrophysics Data System (ADS)

    Abraham, J.; Abreu, P.; Aglietta, M.; Aguirre, C.; Ahn, E. J.; Allard, D.; Allekotte, I.; Allen, J.; Allison, P.; Alvarez-Muñiz, J.; Ambrosio, M.; Anchordoqui, L.; Andringa, S.; Anzalone, A.; Aramo, C.; Argirò, S.; Arisaka, K.; Arneodo, F.; Arqueros, F.; Asch, T.; Asorey, H.; Assis, P.; Aublin, J.; Ave, M.; Avila, G.; Bäcker, T.; Badagnani, D.; Barber, K. B.; Barbosa, A. F.; Barroso, S. L. C.; Baughman, B.; Bauleo, P.; Beatty, J. J.; Beau, T.; Becker, B. R.; Becker, K. H.; Bellétoile, A.; Bellido, J. A.; Benzvi, S.; Berat, C.; Bernardini, P.; Bertou, X.; Biermann, P. L.; Billoir, P.; Blanch-Bigas, O.; Blanco, F.; Bleve, C.; Blümer, H.; Boháčová, M.; Bonifazi, C.; Bonino, R.; Brack, J.; Brogueira, P.; Brown, W. C.; Bruijn, R.; Buchholz, P.; Bueno, A.; Burton, R. E.; Busca, N. G.; Caballero-Mora, K. S.; Caramete, L.; Caruso, R.; Carvalho, W.; Castellina, A.; Catalano, O.; Cazon, L.; Cester, R.; Chauvin, J.; Chiavassa, A.; Chinellato, J. A.; Chou, A.; Chudoba, J.; Chye, J.; Clay, R. W.; Colombo, E.; Conceição, R.; Connolly, B.; Contreras, F.; Coppens, J.; Cordier, A.; Cotti, U.; Coutu, S.; Covault, C. E.; Creusot, A.; Criss, A.; Cronin, J.; Curutiu, A.; Dagoret-Campagne, S.; Daumiller, K.; Dawson, B. R.; de Almeida, R. M.; de Domenico, M.; de Donato, C.; de Jong, S. J.; de La Vega, G.; de Mello Junior, W. J. M.; de Mello Neto, J. R. T.; de Mitri, I.; de Souza, V.; Decerprit, G.; Del Peral, L.; Deligny, O.; Della Selva, A.; Delle Fratte, C.; Dembinski, H.; di Giulio, C.; Diaz, J. C.; Diep, P. N.; Dobrigkeit, C.; D'Olivo, J. C.; Dong, P. N.; Dornic, D.; Dorofeev, A.; Dos Anjos, J. C.; Dova, M. T.; D'Urso, D.; Dutan, I.; Duvernois, M. A.; Engel, R.; Erdmann, M.; Escobar, C. O.; Etchegoyen, A.; Facal San Luis, P.; Falcke, H.; Farrar, G.; Fauth, A. C.; Fazzini, N.; Ferrer, F.; Ferrero, A.; Fick, B.; Filevich, A.; Filipčič, A.; Fleck, I.; Fliescher, S.; Fracchiolla, C. E.; Fraenkel, E. D.; Fulgione, W.; Gamarra, R. F.; Gambetta, S.; García, B.; García Gámez, D.; Garcia-Pinto, D.; Garrido, X.; Gelmini, G.; Gemmeke, H.; Ghia, P. L.; Giaccari, U.; Giller, M.; Glass, H.; Goggin, L. M.; Gold, M. S.; Golup, G.; Gomez Albarracin, F.; Gómez Berisso, M.; Gonçalves, P.; Gonçalves Do Amaral, M.; Gonzalez, D.; Gonzalez, J. G.; Góra, D.; Gorgi, A.; Gouffon, P.; Grebe, S.; Grigat, M.; Grillo, A. F.; Guardincerri, Y.; Guarino, F.; Guedes, G. P.; Gutiérrez, J.; Hague, J. D.; Halenka, V.; Hansen, P.; Harari, D.; Harmsma, S.; Harton, J. L.; Haungs, A.; Healy, M. D.; Hebbeker, T.; Hebrero, G.; Heck, D.; Hojvat, C.; Holmes, V. C.; Homola, P.; Hörandel, J. R.; Horneffer, A.; Hrabovský, M.; Huege, T.; Hussain, M.; Iarlori, M.; Insolia, A.; Ionita, F.; Italiano, A.; Jiraskova, S.; Kaducak, M.; Kampert, K. H.; Karova, T.; Kasper, P.; Kégl, B.; Keilhauer, B.; Kemp, E.; Kieckhafer, R. M.; Klages, H. O.; Kleifges, M.; Kleinfeller, J.; Knapik, R.; Knapp, J.; Koang, D.-H.; Krieger, A.; Krömer, O.; Kruppke, D.; Kuempel, D.; Kunka, N.; Kusenko, A.; La Rosa, G.; Lachaud, C.; Lago, B. L.; Leão, M. S. A. B.; Lebrun, D.; Lebrun, P.; Lee, J.; Leigui de Oliveira, M. A.; Lemiere, A.; Letessier-Selvon, A.; Leuthold, M.; Lhenry-Yvon, I.; López, R.; Lopez Agüera, A.; Lozano Bahilo, J.; Lucero, A.; Luna García, R.; Maccarone, M. C.; Macolino, C.; Maldera, S.; Mandat, D.; Mantsch, P.; Mariazzi, A. G.; Maris, I. C.; Marquez Falcon, H. R.; Martello, D.; Martínez, J.; Martínez Bravo, O.; Mathes, H. J.; Matthews, J.; Matthews, J. A. J.; Matthiae, G.; Maurizio, D.; Mazur, P. O.; McEwen, M.; McNeil, R. R.; Medina-Tanco, G.; Melissas, M.; Melo, D.; Menichetti, E.; Menshikov, A.; Meyhandan, R.; Micheletti, M. I.; Miele, G.; Miller, W.; Miramonti, L.; Mollerach, S.; Monasor, M.; Monnier Ragaigne, D.; Montanet, F.; Morales, B.; Morello, C.; Moreno, J. C.; Morris, C.; Mostafá, M.; Mueller, S.; Muller, M. A.; Mussa, R.; Navarra, G.; Navarro, J. L.; Navas, S.; Necesal, P.; Nellen, L.; Newman-Holmes, C.; Newton, D.; Nhung, P. T.; Nierstenhoefer, N.; Nitz, D.; Nosek, D.; Nožka, L.; Oehlschläger, J.; Olinto, A.; Olmos-Gilbaja, V. M.; Ortiz, M.; Ortolani, F.; Pacheco, N.; Pakk Selmi-Dei, D.; Palatka, M.; Pallotta, J.; Parente, G.; Parizot, E.; Parlati, S.; Pastor, S.; Patel, M.; Paul, T.; Pavlidou, V.; Payet, K.; Pech, M.; Pȩkala, J.; Pelayo, R.; Pepe, I. M.; Perrone, L.; Pesce, R.; Petermann, E.; Petrera, S.; Petrinca, P.; Petrolini, A.; Petrov, Y.; Petrovic, J.; Pfendner, C.; Pichel, A.; Piegaia, R.; Pierog, T.; Pimenta, M.; Pinto, T.; Pirronello, V.; Pisanti, O.; Platino, M.; Pochon, J.; Ponce, V. H.; Pontz, M.; Privitera, P.; Prouza, M.; Quel, E. J.; Rautenberg, J.; Ravignani, D.; Redondo, A.; Reucroft, S.; Revenu, B.; Rezende, F. A. S.; Ridky, J.; Riggi, S.; Risse, M.; Rivière, C.; Rizi, V.; Robledo, C.; Rodriguez, G.; Rodriguez Martino, J.; Rodriguez Rojo, J.; Rodriguez-Cabo, I.; Rodríguez-Frías, M. D.; Ros, G.; Rosado, J.; Roth, M.; Rouillé-D'Orfeuil, B.; Roulet, E.; Rovero, A. C.; Salamida, F.; Salazar, H.; Salina, G.; Sánchez, F.; Santander, M.; Santo, C. E.; Santos, E. M.; Sarazin, F.; Sarkar, S.; Sato, R.; Scharf, N.; Scherini, V.; Schieler, H.; Schiffer, P.; Schmidt, A.; Schmidt, F.; Schmidt, T.; Scholten, O.; Schoorlemmer, H.; Schovancova, J.; Schovánek, P.; Schroeder, F.; Schulte, S.; Schüssler, F.; Schuster, D.; Sciutto, S. J.; Scuderi, M.; Segreto, A.; Semikoz, D.; Settimo, M.; Shellard, R. C.; Sidelnik, I.; Siffert, B. B.; Smetniansky de Grande, N.; Smiałkowski, A.; Šmída, R.; Smith, B. E.; Snow, G. R.; Sommers, P.; Sorokin, J.; Spinka, H.; Squartini, R.; Strazzeri, E.; Stutz, A.; Suarez, F.; Suomijärvi, T.; Supanitsky, A. D.; Sutherland, M. S.; Swain, J.; Szadkowski, Z.; Tamashiro, A.; Tamburro, A.; Tarutina, T.; Taşcău, O.; Tcaciuc, R.; Tcherniakhovski, D.; Thao, N. T.; Thomas, D.; Ticona, R.; Tiffenberg, J.; Timmermans, C.; Tkaczyk, W.; Todero Peixoto, C. J.; Tomé, B.; Tonachini, A.; Torres, I.; Travnicek, P.; Tridapalli, D. B.; Tristram, G.; Trovato, E.; Tuci, V.; Tueros, M.; Ulrich, R.; Unger, M.; Urban, M.; Valdés Galicia, J. F.; Valiño, I.; Valore, L.; van den Berg, A. M.; van Elewyck, V.; Vázquez, R. A.; Veberič, D.; Velarde, A.; Venters, T.; Verzi, V.; Videla, M.; Villaseñor, L.; Vorobiov, S.; Voyvodic, L.; Wahlberg, H.; Wahrlich, P.; Wainberg, O.; Warner, D.; Watson, A. A.; Westerhoff, S.; Whelan, B. J.; Wieczorek, G.; Wiencke, L.; Wilczyńska, B.; Wilczyński, H.; Wileman, C.; Winnick, M. G.; Wu, H.; Wundheiler, B.; Younk, P.; Yuan, G.; Zas, E.; Zavrtanik, D.; Zavrtanik, M.; Zaw, I.; Zepeda, A.; Ziolkowski, M.

    2009-05-01

    Data collected at the Pierre Auger Observatory are used to establish an upper limit on the diffuse flux of tau neutrinos in the cosmic radiation. Earth-skimming ντ may interact in the Earth’s crust and produce a τ lepton by means of charged-current interactions. The τ lepton may emerge from the Earth and decay in the atmosphere to produce a nearly horizontal shower with a typical signature, a persistent electromagnetic component even at very large atmospheric depths. The search procedure to select events induced by τ decays against the background of normal showers induced by cosmic rays is described. The method used to compute the exposure for a detector continuously growing with time is detailed. Systematic uncertainties in the exposure from the detector, the analysis, and the involved physics are discussed. No τ neutrino candidates have been found. For neutrinos in the energy range 2×1017eV

  7. Tau polarisation at LEP

    NASA Astrophysics Data System (ADS)

    Alemany, Ricard

    1999-04-01

    The measurements of the tau polarisation at LEP I are reviewed. Special emphasis is given to the new preliminary results presented at this conference. The ALEPH collaboration has studied the polarisation as a function of the polar angle using a new method based on the tau direction reconstruction and fully exploiting the angular correlations. A second traditional approach, based on the single tau decays has been also developed. The DELPHI collaboration has also studied the full data sample using an individual tau decay method and an inclusive hadronic selection. The results from the four experiments are presented with discussion of the compatibility among the methods and experiments.

  8. Pioglitazone prevents tau oligomerization.

    PubMed

    Hamano, Tadanori; Shirafuji, Norimichi; Makino, Chiemi; Yen, Shu-Hui; Kanaan, Nicholas M; Ueno, Asako; Suzuki, Jinya; Ikawa, Masamichi; Matsunaga, Akiko; Yamamura, Osamu; Kuriyama, Masaru; Nakamoto, Yasunari

    2016-09-23

    Tau aggregation and amyloid β protein (Aβ) deposition are the main causes of Alzheimer's disease (AD). Peroxisome proliferator-activated receptor γ (PPARγ) activation modulates Aβ production. To test whether the PPARγ agonist pioglitazone (PIO) is also effective in preventing tau aggregation in AD, we used a cellular model in which wild-type tau protein (4R0N) is overexpressed (M1C cells) (Hamano et al., 2012) as well as primary neuronal cultures. PIO reduced both phosphorylated and total tau levels, and inactivated glycogen synthase kinase 3β, a major tau kinase, associated with activation of Akt. In addition, PIO decreased cleaved caspase3 and C-terminal truncated tau species by caspase, which is expected to decrease tau aggregation. A fractionation study showed that PIO reduced high molecular-weight (120 kDa), oligomeric tau species in Tris Insoluble, sarkosyl-soluble fractions. Tau decrease was reversed by adding GW9662, a PPARγ antagonist. Together, our current results support the idea that PPARγ agonists may be useful therapeutic agents for AD.

  9. [Tau Positron Emission Tomography].

    PubMed

    Higuchi, Makoto

    2017-07-01

    Accumulation of fibrillar tau protein aggregates is a neuropathological hallmark of Alzheimer's disease (AD) and related neurodegenerative dementias, including a subgroup of frontotemporal lobar degeneration (FTLD). Visualization of tau lesions in the brains of living subjects enables a pathology-based diagnosis of dementing illnesses in the prodromal stage, and offers objective measures of disease progression and outcomes of disease-modifying therapies. With this rationale, diverse classes of low-molecular-weight chemicals capable of binding to a β-pleated sheet structure have been developed to be used for in vivo positron emission tomography (PET) of tau pathologies. Clinical PET studies of AD patients with such tau probes have provided the following insights: (1) Tau fibrils accumulate in the hippocampal formation in an age-dependent manner that is independent of amyloid-beta peptide (Aβ) pathology; (2) The deposition of Aβ may trigger a spatial expansion of tau pathology, in transition from normal aging to advanced AD; and (3) Tau accumulation is intimately associated with local neuronal loss, leading to cortical atrophy and focal symptoms. In contrast, studies of FTLD have shown a limited performance of first-generation PET probes in capturing non-AD-type tau lesions. New compounds have accordingly been developed and clinically tested, proving to yield a high contrast for tau deposits with high specificity. These second-generation probes are being evaluated primarily by pharmaceutical companies, in line with their growing demands for neuroimaging-based biomarkers serving for clinical trials of anti-Aβ and anti-tau therapies. Meanwhile, a consortium flexibly linking academia and industry to facilitate the utilization of research tools, including tau PET probes, has been established in Japan, for the ultimate purpose of elucidating the molecular etiology of tauopathies and creating diagnostic and therapeutic agents based on such an understanding.

  10. Measurement of the tau lifetime

    SciTech Connect

    Jaros, J.A.

    1982-10-01

    If the tau lepton couples to the charged weak current with universal strength, its lifetime can be expressed in terms of the muon's lifetime, the ratio of the masses of the muon and the tau, and the tau's branching ratio into e anti nu/sub e/ nu/sub tau/ as tau/sub tau/ = tau/sub ..mu../ (m/sub ..mu..//m/sub tau/)/sup 5/ B(tau ..-->.. e anti nu/sub e/nu/sub tau/) = 2.8 +- 0.2 x 10/sup -13/ s. This paper describes the measurement of the tau lifetime made by the Mark II collaboration, using a new high precision drift chamber in contunction with the Mark II detector at PEP. The results of other tau lifetime measurements are summarized.

  11. A Perspective on Tau Physics

    SciTech Connect

    Kim, Peter C

    1998-11-10

    It will soon be the twenty fifth anniversary of the discovery of the tau lepton. It has been an amazing twenty five years for tau physics and for the strong interaction physics that can be deduced from studies of tau decays. The discovery of the tau was based on the elucidation of the nature of about one hundred tau pairs. At this Fifth International Workshop on Tau Lepton Physics new results in tau physics are based on hundreds of thousands or even millions of tau pairs. In the next two decades we will see the data on tau pairs increase by at least a factor of ten. The theoretical work and theoretical understanding of tau physics and tau neutrino physics has also expanded enormously, and this theory will continue to grow in its reach and its depth. Given the vastness of this field and the recognition that there is always great uncertainty in predicting future directions and accomplishments in a scientific field; any perspective of the future of a scientific field is substantially dependent on the author's opinions and guesses. I have limited this talk to seven topics: tau research facilities in the next decades, searching for unexpected tau decay modes, searching for additional tau decay mechanisms, radiative tau decays, tau decay modes of the W, B, and D, searching for CP violation in tau decay, and rethinking the Tau-Charm factory.

  12. Skimming Digits: Neuromorphic Classification of Spike-Encoded Images

    PubMed Central

    Cohen, Gregory K.; Orchard, Garrick; Leng, Sio-Hoi; Tapson, Jonathan; Benosman, Ryad B.; van Schaik, André

    2016-01-01

    The growing demands placed upon the field of computer vision have renewed the focus on alternative visual scene representations and processing paradigms. Silicon retinea provide an alternative means of imaging the visual environment, and produce frame-free spatio-temporal data. This paper presents an investigation into event-based digit classification using N-MNIST, a neuromorphic dataset created with a silicon retina, and the Synaptic Kernel Inverse Method (SKIM), a learning method based on principles of dendritic computation. As this work represents the first large-scale and multi-class classification task performed using the SKIM network, it explores different training patterns and output determination methods necessary to extend the original SKIM method to support multi-class problems. Making use of SKIM networks applied to real-world datasets, implementing the largest hidden layer sizes and simultaneously training the largest number of output neurons, the classification system achieved a best-case accuracy of 92.87% for a network containing 10,000 hidden layer neurons. These results represent the highest accuracies achieved against the dataset to date and serve to validate the application of the SKIM method to event-based visual classification tasks. Additionally, the study found that using a square pulse as the supervisory training signal produced the highest accuracy for most output determination methods, but the results also demonstrate that an exponential pattern is better suited to hardware implementations as it makes use of the simplest output determination method based on the maximum value. PMID:27199646

  13. Tau protein and tau aggregation inhibitors.

    PubMed

    Bulic, Bruno; Pickhardt, Marcus; Mandelkow, Eva-Maria; Mandelkow, Eckhard

    2010-01-01

    Alzheimer disease is characterized by pathological aggregation of two proteins, tau and Abeta-amyloid, both of which are considered to be toxic to neurons. In this review we summarize recent advances on small molecule inhibitors of protein aggregation with emphasis on tau, with activities mediated by the direct interference of self-assembly. The inhibitors can be clustered in several compound classes according to their chemical structure, with subsequent description of the structure-activity relationships, showing that hydrophobic interactions are prevailing. The description is extended to the pharmacological profile of the compounds in order to evaluate their drug-likeness, with special attention to toxicity and bioavailability. The collected data indicate that following the improvements of the in vitro inhibitory potencies, the consideration of the in vivo pharmacokinetics is an absolute prerequisite for the development of compounds suitable for a transfer from bench to bedside.

  14. Measurements of the tau Mass and Mass Difference of the tau^+ and tau^- at BABAR

    SciTech Connect

    Aubert, B.; Karyotakis, Y.; Lees, J.P.; Poireau, V.; Prencipe, E.; Prudent, X.; Tisserand, V.; Garra Tico, J.; Grauges, E.; Martinelli, M.; Palano, A.; Pappagallo, M.; Eigen, G.; Stugu, B.; Sun, L.; Battaglia, M.; Brown, D.N.; Kerth, L.T.; Kolomensky, Yu.G.; Lynch, G.; Osipenkov, I.L.; /UC, Berkeley /Birmingham U. /Ruhr U., Bochum /British Columbia U. /Brunel U. /Novosibirsk, IYF /UC, Irvine /UC, Riverside /UC, San Diego /UC, Santa Barbara /UC, Santa Cruz /Caltech /Cincinnati U. /Colorado U. /Colorado State U. /Dortmund U. /Dresden, Tech. U. /Ecole Polytechnique /Edinburgh U. /INFN, Ferrara /Ferrara U. /INFN, Ferrara /INFN, Ferrara /Ferrara U. /INFN, Ferrara /INFN, Ferrara /Ferrara U. /Frascati /INFN, Genoa /Genoa U. /INFN, Genoa /INFN, Genoa /Genoa U. /INFN, Genoa /INFN, Genoa /Genoa U. /Harvard U. /Heidelberg U. /Humboldt U., Berlin /Imperial Coll., London /Iowa State U. /Iowa State U. /Johns Hopkins U. /Orsay, LAL /LLNL, Livermore /Liverpool U. /Queen Mary, U. of London /Royal Holloway, U. of London /Louisville U. /Mainz U., Inst. Kernphys. /Manchester U. /Maryland U. /Massachusetts U., Amherst /MIT /McGill U. /INFN, Milan /Milan U. /INFN, Milan /INFN, Milan /Milan U. /Mississippi U. /Montreal U. /Mt. Holyoke Coll. /INFN, Naples /Naples U. /INFN, Naples /INFN, Naples /Naples U. /NIKHEF, Amsterdam /NIKHEF, Amsterdam /Notre Dame U. /Ohio State U. /Oregon U. /INFN, Padua /Padua U. /INFN, Padua /INFN, Padua /Padua U. /Paris U., VI-VII /Pennsylvania U. /INFN, Perugia /Perugia U. /INFN, Pisa /Pisa U. /INFN, Pisa /Pisa, Scuola Normale Superiore /INFN, Pisa /Pisa U. /INFN, Pisa /Princeton U. /INFN, Rome /INFN, Rome /Rome U. /INFN, Rome /INFN, Rome /Rome U. /INFN, Rome /INFN, Rome /Rome U. /INFN, Rome /INFN, Rome /Rome U. /INFN, Rome /Rostock U. /Rutherford /DAPNIA, Saclay /SLAC /South Carolina U. /Stanford U., Phys. Dept. /SUNY, Albany /Tel Aviv U. /Tennessee U. /Texas U. /Texas U., Dallas /INFN, Turin /Turin U. /INFN, Trieste /Trieste U. /Valencia U. /Victoria U. /Warwick U. /Wisconsin U., Madison

    2009-10-30

    The authors present the result of a precision measurement of the mass of the {tau} lepton, M{sub {tau}}, based on 423 fb{sup -1} of data recorded at the {Upsilon}(4S) resonance with the BABAR detector. Using a pseudomass endpoint method, they determine the mass to be 1776.68 {+-} 0.12(stat) {+-} 0.41(syst) MeV. They also measure the mass difference between the {tau}{sup +} and {tau}{sup -}, and obtain (M{sub {tau}{sup +}} - M{sub {tau}{sup -}})/M{sub AVG}{sup {tau}} = (-3.4 {+-} 1.3(stat) {+-} 0.3(syst)) x 10{sup -4}, where M{sub AVG}{sup {tau}} is the average value of M{sub {tau}{sup +}} and M{sub {tau}{sup -}}.

  15. Earth

    NASA Image and Video Library

    2012-01-30

    Behold one of the more detailed images of the Earth yet created. This Blue Marble Earth montage shown above -- created from photographs taken by the Visible/Infrared Imager Radiometer Suite (VIIRS) instrument on board the new Suomi NPP satellite -- shows many stunning details of our home planet. The Suomi NPP satellite was launched last October and renamed last week after Verner Suomi, commonly deemed the father of satellite meteorology. The composite was created from the data collected during four orbits of the robotic satellite taken earlier this month and digitally projected onto the globe. Many features of North America and the Western Hemisphere are particularly visible on a high resolution version of the image. http://photojournal.jpl.nasa.gov/catalog/PIA18033

  16. Hyperphosphorylation-induced tau oligomers.

    PubMed

    Iqbal, Khalid; Gong, Cheng-Xin; Liu, Fei

    2013-01-01

    In normal adult brain the microtubule associated protein (MAP) tau contains 2-3 phosphates per mol of the protein and at this level of phosphorylation it is a soluble cytosolic protein. The normal brain tau interacts with tubulin and promotes its assembly into microtubules and stabilizes these fibrils. In Alzheimer disease (AD) brain tau is three to fourfold hyperphosphorylated. The abnormally hyperphosphorylated tau binds to normal tau instead of the tubulin and this binding leads to the formation of tau oligomers. The tau oligomers can be sedimented at 200,000 × g whereas the normal tau under these conditions remains in the supernatant. The abnormally hyperphosphorylated tau is capable of sequestering not only normal tau but also MAP MAP1 and MAP2 and causing disruption of the microtubule network promoted by these proteins. Unlike Aβ and prion protein (PrP) oligomers, tau oligomerization in AD and related tauopathies is hyperphosphorylation-dependent; in vitro dephosphorylation of AD P-tau with protein phosphatase 2A (PP2A) inhibits and rehyperphosphorylation of the PP2A-AD P-tau with more than one combination of tau protein kinases promotes its oligomerization. In physiological assembly conditions the AD P-tau readily self-assembles into paired helical filaments. Missense tau mutations found in frontotemporal dementia apparently lead to tau oligomerization and neurofibrillary pathology by promoting its abnormal hyperphosphorylation. Dysregulation of the alternative splicing of tau that alters the 1:1 ratio of the 3-repeat: 4-repeat taus such as in Down syndrome, Pick disease, and progressive supranuclear palsy leads to the abnormal hyperphosphorylation of tau.

  17. 21 CFR 133.157 - Part-skim mozzarella and scamorza cheese.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Part-skim mozzarella and scamorza cheese. 133.157... (CONTINUED) FOOD FOR HUMAN CONSUMPTION CHEESES AND RELATED CHEESE PRODUCTS Requirements for Specific Standardized Cheese and Related Products § 133.157 Part-skim mozzarella and scamorza cheese. Part-skim...

  18. 21 CFR 133.157 - Part-skim mozzarella and scamorza cheese.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Part-skim mozzarella and scamorza cheese. 133.157... (CONTINUED) FOOD FOR HUMAN CONSUMPTION CHEESES AND RELATED CHEESE PRODUCTS Requirements for Specific Standardized Cheese and Related Products § 133.157 Part-skim mozzarella and scamorza cheese. Part-skim...

  19. TAU as Tao. [interstellar spacecraft performance

    NASA Technical Reports Server (NTRS)

    Lyman, P. T.; Reid, M. S.

    1989-01-01

    This paper discusses the feasibility of building and launching a truly deep-space spacecraft mission that will penetrate near interstellar space to a depth of one thousand astronomical units (TAU) within a flight time of 50 years. Particular attention is given to the mission profile and to its communications system, power system, and propulsion system. Results of experimental studies indicate that, with advanced technology, reasonable trip times can be achieved and adequate science information can be brought to earth.

  20. Tau physics results from SLD

    SciTech Connect

    Daoudi, M.; SLD Collaboration

    1996-08-10

    Results on {tau} physics at SLD are presented. They are based on 4,316 {tau}-pair events selected from a 150 k Z{sup 0} data sample collected at the SLC. These results include measurements of the {tau} lifetime ({tau}{sub r} = 288.1 {+-} 6.1 {+-} 3.3 fs), the {tau} Michel parameters ({rho} = 0.71 {+-} 0.09 {+-} 0.04, {zeta} = 1.03 {+-} 0.36 {+-} 0.05, and {zeta}{delta} = 0.84 {+-} 0.27 {+-} 0.05), and the {tau} neutrino helicity (h{sub {nu}} = {minus}0.81 {+-} 0.18 {+-} 0.03).

  1. Counter-current carbon dioxide extraction of soy skim

    USDA-ARS?s Scientific Manuscript database

    The use of carbon dioxide in a counter-current fractionation column was investigated as a means to remove residual fat from soy skim after enzyme-assisted aqueous extraction of soybeans. The stainless steel column was 1.2 meters long with an internal diameter of 1.75 cm and filled protruded stainles...

  2. 21 CFR 133.191 - Part-skim spiced cheeses.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Part-skim spiced cheeses. 133.191 Section 133.191 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD... definition and standard of identity, and are subject to the requirements for label statement of...

  3. 21 CFR 133.191 - Part-skim spiced cheeses.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Part-skim spiced cheeses. 133.191 Section 133.191 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD... definition and standard of identity, and are subject to the requirements for label statement of...

  4. 21 CFR 133.188 - Semisoft part-skim cheeses.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    .... They are made from partly skimmed milk and other ingredients specified in this section, by the... the methods set forth in § 133.5 (a), (b), and (d). If the milk used is not pasteurized, the cheese so made is cured at a temperature of not less than 35 °F, for not less than 60 days. (b) Milk, which...

  5. Nisin Production Utilizing Skimmed Milk Aiming to Reduce Process Cost

    NASA Astrophysics Data System (ADS)

    Jozala, Angela Faustino; de Andrade, Maura Sayuri; de Arauz, Luciana Juncioni; Pessoa, Adalberto; Penna, Thereza Christina Vessoni

    Nisin is a natural additive for conservation of food, pharmaceutical, and dental products and can be used as a therapeutic agent. Nisin inhibits the outgrowth of spores, the growth of a variety of Gram-positive and Gram-negative bacteria. This study was performed to optimize large-scale nisin production in skimmed milk and subproducts aiming at low-costs process and stimulating its utilization. Lactococcus lactis American Type Culture Collection (ATCC) 11454 was developed in a rotary shaker (30°C/36 h/100 rpm) in diluted skimmed milk and nisin activity, growth parameters, and media components were also studied. Nisin activity in growth media was expressed in arbitrary units (AU/mL) and converted to standard nisin concentration (Nisaplin®, 25 mg of pure nisin is 1.0×106 AU/mL). Nisin activity in skimmed milk 2.27 gtotal solids was up to threefold higher than transfers in skimmed milk 4.54 gtotal solids and was up to 85-fold higher than transfers in skimmed milk 1.14 gtotal solids. L. lactis was assayed in a New Brunswick fermentor with 1.5 L of diluted skimmed milk (2.27 gtotal solids) and airflow of 1.5 mL/min (30°C/36/200 rpm), without pH control. In this condition nisin activity was observed after 4 h (45.07 AU/mL) and in the end of 36 h process (3312.07 AU/mL). This work shows the utilization of a low-cost growth medium (diluted skimmed milk) to nisin production with wide applications. Furthermore, milk subproducts (milk whey) can be exploited in nisin production, because in Brazil 50% of milk whey is disposed with no treatment in rivers and because of high organic matter concentrations it is considered an important pollutant. In this particular case an optimized production of an antimicrobial would be lined up with industrial disposal recycling.

  6. Zinc Binding Directly Regulates Tau Toxicity Independent of Tau Hyperphosphorylation

    PubMed Central

    Huang, Yunpeng; Wu, Zhihao; Cao, Yu; Lang, Minglin; Lu, Bingwei; Zhou, Bing

    2015-01-01

    SUMMARY Tau hyperphosphorylation is thought to underlie tauopathy. Working in a Drosophila tauopathy model expressing a human Tau mutant (hTauR406W, or Tau*), we show that zinc contributes to the development of Tau toxicity through two independent actions: by increasing Tau phosphorylation and, more significantly, by directly binding to Tau. Elimination of zinc binding through amino acid substitution of Cys residues has a minimal effect on phosphorylation levels yet essentially eliminates Tau toxicity. The toxicity of the zinc-binding-deficient mutant Tau* (Tau*C2A) and overexpression of native Drosophila Tau, also lacking the corresponding zinc-binding Cys residues, are largely impervious to zinc concentration. Importantly, restoration of zinc-binding ability to Tau* by introduction of a zinc-binding residue (His) into the original Cys positions restores zinc-responsive toxicities in proportion to zinc-binding affinities. These results indicate zinc binding is a substantial contributor to tauopathy and have implications for therapy development. PMID:25066125

  7. Review of tau lepton decays

    SciTech Connect

    Stoker, D.P.

    1991-07-01

    Measurements of the {tau} decay modes are reviewed and compared with the predictions of the Standard Model. While the agreement is generally good, the status of the 1-prong puzzle'' remains controversial and a discrepancy between the measured leptonic branching fractions and the {tau} lifetime persists. Prospects for precision measurements at a Tau-Charm Factory are also reviewed. 20 refs., 2 tabs.

  8. Rennet-induced aggregation and curd formation from skimmed milk powders prepared under different sterilizing conditions.

    PubMed

    Miyamoto, Yuka; Matsumiya, Kentaro; Kubouchi, Hiroaki; Noda, Masayuki; Nishimura, Kimio; Matsumura, Yasuki

    2009-09-01

    Heat treatment during the production of skimmed milk powder causes denaturation of proteins, thereby affecting the physicochemical properties of the skimmed milk powder. To understand the effects of heat treatment on the sensitivity of the casein micelles in skimmed milk powders, low heating type (L), normal heating type (N), high heating type (H), and super-high heating type (SH), to reaction with rennet, rennet-induced curd formation was investigated. A well-developed network structure with wide spaces was observed only in the curd derived from the solution of type L skimmed milk powder. SDS-PAGE suggested that there was no difference in the amount of glycomacropeptide generated from kappa-casein in the four types of skimmed milk powder, but casein micelles in the solution of type L skimmed milk powder formed aggregates most effectively. These results are discussed with respect to the thermal denaturation of proteins in skimmed milk powder.

  9. Effect of soy skim from soybean aqueous processing on the performance of corn ethanol fermentation.

    PubMed

    Yao, Linxing; Wang, Tong; Wang, Hui

    2011-10-01

    The feasibility of using soy skim, a co-product of the aqueous processing of soybeans, in ethanol production from corn was evaluated. Specific growth rates were compared when Saccharomyces cerevisiae was grown in soy skim and peptone-yeast extract media supplemented with glucose. Such soy skim was proved to be a good nitrogen source for yeast growth. Next, fermentation of dry-ground corn to ethanol using soy skim as the media was simulated on 1.5-L scale. Replacing water with soy skim increased the initial ethanol production rates by 4-32% while final ethanol yield was about 39 g/100 g dry corn, similar to the result when water was used. Solid and protein contents in the finished beer increased with the addition of soy skim. Thus, replacing water in corn-ethanol fermentation with soy skim is feasible, and may improve the economics of both aqueous soybean processing and corn ethanol fermentation.

  10. Did Pterosaurs Feed by Skimming? Physical Modelling and Anatomical Evaluation of an Unusual Feeding Method

    PubMed Central

    Humphries, Stuart; Bonser, Richard H. C; Witton, Mark P; Martill, David M

    2007-01-01

    Similarities between the anatomies of living organisms are often used to draw conclusions regarding the ecology and behaviour of extinct animals. Several pterosaur taxa are postulated to have been skim-feeders based largely on supposed convergences of their jaw anatomy with that of the modern skimming bird, Rynchops spp. Using physical and mathematical models of Rynchops bills and pterosaur jaws, we show that skimming is considerably more energetically costly than previously thought for Rynchops and that pterosaurs weighing more than one kilogram would not have been able to skim at all. Furthermore, anatomical comparisons between the highly specialised skull of Rynchops and those of postulated skimming pterosaurs suggest that even smaller forms were poorly adapted for skim-feeding. Our results refute the hypothesis that some pterosaurs commonly used skimming as a foraging method and illustrate the pitfalls involved in extrapolating from limited morphological convergence. PMID:17676976

  11. Did pterosaurs feed by skimming? Physical modelling and anatomical evaluation of an unusual feeding method.

    PubMed

    Humphries, Stuart; Bonser, Richard H C; Witton, Mark P; Martill, David M

    2007-08-01

    Similarities between the anatomies of living organisms are often used to draw conclusions regarding the ecology and behaviour of extinct animals. Several pterosaur taxa are postulated to have been skim-feeders based largely on supposed convergences of their jaw anatomy with that of the modern skimming bird, Rynchops spp. Using physical and mathematical models of Rynchops bills and pterosaur jaws, we show that skimming is considerably more energetically costly than previously thought for Rynchops and that pterosaurs weighing more than one kilogram would not have been able to skim at all. Furthermore, anatomical comparisons between the highly specialised skull of Rynchops and those of postulated skimming pterosaurs suggest that even smaller forms were poorly adapted for skim-feeding. Our results refute the hypothesis that some pterosaurs commonly used skimming as a foraging method and illustrate the pitfalls involved in extrapolating from limited morphological convergence.

  12. Measurements of the decays tau/sup -/. -->. rho/sup -/. nu. /sub tau/, tau/sup -/. -->. pi. /sup -/. nu. /sub tau/ and tau/sup -/. -->. K*-(892). nu. /sub tau/ using the MARK II detector at SPEAR

    SciTech Connect

    Dorfan, J.

    1981-04-01

    Measurements of the branching fractions for the Cabibbo favored decays tau/sup -/ ..-->.. rho/sup -/ ..-->.. ..pi../sup -/..nu../sub tau/ and the Cabibbo suppressed decay mode tau/sup -/ ..-->.. K*/sup -/ (892)..nu../sub tau/ are presented. The energy dependence of the tau/sup +/tau/sup -/ production cross section is obtained for the decays tau/sup -/ ..-->.. rho/sup -/..nu../sub tau/ and these spectra agree well with the classification of the tau/sup -/ as a spin-1/2 point particle. Fits to the production cross section yield a measurement of M/sub tau/ = (1787 +- 10) MeV/c/sup 2/ for the tau mass. Ninety-five percent confidence upper limits for the forbidden decay tau/sup -/ ..-->.. K*/sup -/(1430)..nu../sub tau/ and the tau neutrino mass are presented.

  13. Neuronal activity enhances tau propagation and tau pathology in vivo.

    PubMed

    Wu, Jessica W; Hussaini, S Abid; Bastille, Isle M; Rodriguez, Gustavo A; Mrejeru, Ana; Rilett, Kelly; Sanders, David W; Cook, Casey; Fu, Hongjun; Boonen, Rick A C M; Herman, Mathieu; Nahmani, Eden; Emrani, Sheina; Figueroa, Y Helen; Diamond, Marc I; Clelland, Catherine L; Wray, Selina; Duff, Karen E

    2016-08-01

    Tau protein can transfer between neurons transneuronally and trans-synaptically, which is thought to explain the progressive spread of tauopathy observed in the brain of patients with Alzheimer's disease. Here we show that physiological tau released from donor cells can transfer to recipient cells via the medium, suggesting that at least one mechanism by which tau can transfer is via the extracellular space. Neuronal activity has been shown to regulate tau secretion, but its effect on tau pathology is unknown. Using optogenetic and chemogenetic approaches, we found that increased neuronal activity stimulates the release of tau in vitro and enhances tau pathology in vivo. These data have implications for disease pathogenesis and therapeutic strategies for Alzheimer's disease and other tauopathies.

  14. Boronate-tau mediated uptake in neurons.

    PubMed

    Pérez, Mar; Cuadros, Raquel; Pallas-Bazarra, Noemi; García, Carlos; Langa, Elena; Jurado-Arjona, Jerónimo; Hernández, Félix; Avila, Jesús

    2014-01-01

    We modified tau protein with boronic acid to facilitate its delivery into non neural or neural cultured cells lacking tau protein. Our results indicate that the incorporated tau promotes the formation of cytoplasmic extensions in non-neuronal cells, as well as the appearance of neurites in cultured tau knockout hippocampal neurons. In addition, boronated tau is incorporated into hippocampal neurons of tau knockout mice after intracranial injection in vivo. These findings describe a novel method to deliver exogenous tau protein into cells.

  15. Plasma tau in Alzheimer disease.

    PubMed

    Mattsson, Niklas; Zetterberg, Henrik; Janelidze, Shorena; Insel, Philip S; Andreasson, Ulf; Stomrud, Erik; Palmqvist, Sebastian; Baker, David; Tan Hehir, Cristina A; Jeromin, Andreas; Hanlon, David; Song, Linan; Shaw, Leslie M; Trojanowski, John Q; Weiner, Michael W; Hansson, Oskar; Blennow, Kaj

    2016-10-25

    To test whether plasma tau is altered in Alzheimer disease (AD) and whether it is related to changes in cognition, CSF biomarkers of AD pathology (including β-amyloid [Aβ] and tau), brain atrophy, and brain metabolism. This was a study of plasma tau in prospectively followed patients with AD (n = 179), patients with mild cognitive impairment (n = 195), and cognitive healthy controls (n = 189) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and cross-sectionally studied patients with AD (n = 61), mild cognitive impairment (n = 212), and subjective cognitive decline (n = 174) and controls (n = 274) from the Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably (BioFINDER) study at Lund University, Sweden. A total of 1284 participants were studied. Associations were tested between plasma tau and diagnosis, CSF biomarkers, MRI measures, (18)fluorodeoxyglucose-PET, and cognition. Higher plasma tau was associated with AD dementia, higher CSF tau, and lower CSF Aβ42, but the correlations were weak and differed between ADNI and BioFINDER. Longitudinal analysis in ADNI showed significant associations between plasma tau and worse cognition, more atrophy, and more hypometabolism during follow-up. Plasma tau partly reflects AD pathology, but the overlap between normal aging and AD is large, especially in patients without dementia. Despite group-level differences, these results do not support plasma tau as an AD biomarker in individual people. Future studies may test longitudinal plasma tau measurements in AD. © 2016 American Academy of Neurology.

  16. Plasma tau in Alzheimer disease

    PubMed Central

    Zetterberg, Henrik; Janelidze, Shorena; Insel, Philip S.; Andreasson, Ulf; Stomrud, Erik; Palmqvist, Sebastian; Baker, David; Tan Hehir, Cristina A.; Jeromin, Andreas; Hanlon, David; Song, Linan; Shaw, Leslie M.; Trojanowski, John Q.; Weiner, Michael W.; Hansson, Oskar; Blennow, Kaj

    2016-01-01

    Objective: To test whether plasma tau is altered in Alzheimer disease (AD) and whether it is related to changes in cognition, CSF biomarkers of AD pathology (including β-amyloid [Aβ] and tau), brain atrophy, and brain metabolism. Methods: This was a study of plasma tau in prospectively followed patients with AD (n = 179), patients with mild cognitive impairment (n = 195), and cognitive healthy controls (n = 189) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and cross-sectionally studied patients with AD (n = 61), mild cognitive impairment (n = 212), and subjective cognitive decline (n = 174) and controls (n = 274) from the Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably (BioFINDER) study at Lund University, Sweden. A total of 1284 participants were studied. Associations were tested between plasma tau and diagnosis, CSF biomarkers, MRI measures, 18fluorodeoxyglucose-PET, and cognition. Results: Higher plasma tau was associated with AD dementia, higher CSF tau, and lower CSF Aβ42, but the correlations were weak and differed between ADNI and BioFINDER. Longitudinal analysis in ADNI showed significant associations between plasma tau and worse cognition, more atrophy, and more hypometabolism during follow-up. Conclusions: Plasma tau partly reflects AD pathology, but the overlap between normal aging and AD is large, especially in patients without dementia. Despite group-level differences, these results do not support plasma tau as an AD biomarker in individual people. Future studies may test longitudinal plasma tau measurements in AD. PMID:27694257

  17. Dopa Decarboxylase Modulates Tau Toxicity.

    PubMed

    Kow, Rebecca L; Sikkema, Carl; Wheeler, Jeanna M; Wilkinson, Charles W; Kraemer, Brian C

    2017-06-15

    The microtubule-associated protein tau accumulates into toxic aggregates in multiple neurodegenerative diseases. We found previously that loss of D2-family dopamine receptors ameliorated tauopathy in multiple models including a Caenorhabditis elegans model of tauopathy. To better understand how loss of D2-family dopamine receptors can ameliorate tau toxicity, we screened a collection of C. elegans mutations in dopamine-related genes (n = 45) for changes in tau transgene-induced behavioral defects. These included many genes responsible for dopamine synthesis, metabolism, and signaling downstream of the D2 receptors. We identified one dopamine synthesis gene, dopa decarboxylase (DDC), as a suppressor of tau toxicity in tau transgenic worms. Loss of the C. elegans DDC gene, bas-1, ameliorated the behavioral deficits of tau transgenic worms, reduced phosphorylated and detergent-insoluble tau accumulation, and reduced tau-mediated neuron loss. Loss of function in other genes in the dopamine and serotonin synthesis pathways did not alter tau-induced toxicity; however, their function is required for the suppression of tau toxicity by bas-1. Additional loss of D2-family dopamine receptors did not synergize with bas-1 suppression of tauopathy phenotypes. Loss of the DDC bas-1 reduced tau-induced toxicity in a C. elegans model of tauopathy, while loss of no other dopamine or serotonin synthesis genes tested had this effect. Because loss of activity upstream of DDC could reduce suppression of tau by DDC, this suggests the possibility that loss of DDC suppresses tau via the combined accumulation of dopamine precursor levodopa and serotonin precursor 5-hydroxytryptophan. Published by Elsevier Inc.

  18. Vatless manufacturing of low-moisture part-skim mozzarella cheese from highly concentrated skim milk microfiltration retentates.

    PubMed

    Ardisson-Korat, A V; Rizvi, S S H

    2004-11-01

    Low-moisture, part-skim (LMPS) Mozzarella cheeses were made from concentration factor (CF) 6, 7, 8, and 9, pH 6.0 skim milk microfiltration (MF) retentates using a vatless cheese-making process. The compositional and proteolytic effects of cheese made from 4 CF retentates were evaluated as well as their functional properties (meltability and stretchability). Pasteurized skim milk was microfiltered using a 0.1-microm ceramic membrane at 50 degrees C to a retentate CF of 6, 7, 8, and 9. An appropriate amount of cream was added to achieve a constant casein:fat ratio in the 4 cheesemilks. The ratio of rennet to casein was also kept constant in the 4 cheesemilks. The compositional characteristics of the cheeses made from MF retentates did not vary with retentate CF and were within the legal range for LMPS Mozzarella cheese. The observed reduction in whey drained was greater than 90% in the cheese making from the 4 CF retentates studied. The development of proteolytic and functional characteristics was slower in the MF cheeses than in the commercial samples that were used for comparison due to the absence of starter culture, the lower level of rennet used, and the inhibition of cheese proteolysis due to the inhibitory effect of residual whey proteins retained in the MF retentates, particularly high molecular weight fractions.

  19. Decays of the heavy lepton, tau (1785)

    SciTech Connect

    Blocker, C.A.

    1980-04-01

    The structure of the weak hadronic current coupled to the tau is investigated via some of the hadronic decays of the tau. The vector current coupling is determined by measuring the tau ..-->.. rho ..nu../sub tau/ branching ratio. The axial-vector coupling is determined by measuring the tau ..-->.. ..pi.. ..nu../sub tau/ branching ratio. The Cabibbo structure of the hadronic current is established by observing the decay tau ..-->.. K*(890)..nu../sub tau/ and measuring its branching ratio. The branching ratios for the decays tau ..-->.. e anti ..nu../sub e/..nu../sub tau/ and tau ..-->.. ..mu.. anti ..nu../sub ..mu../..nu../sub tau/ are measured as a normalization for the hadronic decays and as a check on the validity of the measurements. The leptonic branching ratios agree well with previous experiments. From a kinematic fit to the pion energy spectrum in the decay tau ..-->.. ..pi.. ..nu../sub tau/, an upper limit (95% confidence level) of 245 MeV is placed on the tau neutrino mass. From a simultaneous fit of the center of mass energy dependence of the tau production cross section and the pion energy spectrum in the decay tau ..-->.. ..pi.. ..nu../sub tau/, the tau mass is determined to be 1.787 +- .010 GeV/c. All properties of the tau measured here are consistent with it being a sequential lepton coupled to the ordinary weak hadronic current.

  20. Image-Based Analysis of Intracellular Tau Aggregation by Using Tau-BiFC Cell Model.

    PubMed

    Lim, Sungsu; Kim, Dohee; Kim, Dong Jin; Kim, Yun Kyung

    2017-01-01

    Abnormal tau aggregation is a pathological hallmark of neurodegenerative disease classified as tauopathy. Preventing tau aggregation becomes an important therapeutic strategy to cure tau-mediated neurodegeneration. Here, we describe a method to investigate intracellular tau aggregation by using a recently developed tau aggregation cell-based model named tau-BiFC. High-throughput and high-contents screening method for quantifying intracellular tau aggregation would expedite the discovery of drugs that inhibit tau aggregation.

  1. Tau physics at future facilities

    SciTech Connect

    Perl, M.L.

    1994-12-01

    This paper dicusses and projects the tau research which may be carried out at CESR, at BEPC, at the SLC, in the next few years at LEP I, at the asymmetric B-factories under construction in Japan and the United States and, if built, a tau-charm factory. As the size of tau data sets increases, there is an increasing need to reduce the effects of systematic errors on the precision and search range of experiments. In most areas of tau physics there is a large amount of progress to be made, but in a few areas it will be difficult to substantially improve the precision of present measurements.

  2. Tau immunotherapy for Alzheimer's disease.

    PubMed

    Pedersen, Jan Torleif; Sigurdsson, Einar M

    2015-06-01

    Targeting pathological tau protein in Alzheimer's disease (AD) and related tauopathies has shown great potential in animal models. Given that tau lesions correlate better with the degree of dementia than do amyloid-β (Aβ) plaques, their clearance may be clinically more efficacious than removing Aβ when cognitive deficits become evident in AD. Several complementary mechanisms of antibody-mediated removal of tau aggregates are likely to act in concert and the importance of each one may depend on antibody properties, the disease, and its stage. Clinical trials of tau immunotherapy are already underway and several more are likely to be initiated in the near future.

  3. Searching for tau neutrinos with Cherenkov telescopes

    NASA Astrophysics Data System (ADS)

    Góra, D.; Bernardini, E.; Kappes, A.

    2015-02-01

    Cherenkov telescopes have the capability of detecting high energy tau neutrinos in the energy range of 1-1000 PeV by searching for very inclined showers. If a tau lepton, produced by a tau neutrino, escapes from the Earth or a mountain, it will decay and initiate a shower in the air which can be detected by an air shower fluorescence or Cherenkov telescope. In this paper, we present detailed Monte Carlo simulations of corresponding event rates for the VERITAS and two proposed Cherenkov Telescope Array sites: Meteor Crater and Yavapai Ranch, which use representative AGN neutrino flux models and take into account topographic conditions of the detector sites. The calculated neutrino sensitivities depend on the observation time and the shape of the energy spectrum, but in some cases are comparable or even better than corresponding neutrino sensitivities of the IceCube detector. For VERITAS and the considered Cherenkov Telescope Array sites the expected neutrino sensitivities are up to factor 3 higher than for the MAGIC site because of the presence of surrounding mountains.

  4. Effects of tau domain-specific antibodies and intravenous immunoglobulin on tau aggregation and aggregate degradation.

    PubMed

    Esteves-Villanueva, Jose O; Trzeciakiewicz, Hanna; Loeffler, David A; Martić, Sanela

    2015-01-20

    Tau pathology, including neurofibrillary tangles, develops in Alzheimer's disease (AD). The aggregation and hyperphosphorylation of tau are potential therapeutic targets for AD. Administration of anti-tau antibodies reduces tau pathology in transgenic "tauopathy" mice; however, the optimal tau epitopes and conformations to target are unclear. Also unknown is whether intravenous immunoglobulin (IVIG) products, currently being evaluated in AD trials, exert effects on pathological tau. This study examined the effects of anti-tau antibodies targeting different tau epitopes and the IVIG Gammagard on tau aggregation and preformed tau aggregates. Tau aggregation was assessed by transmission electron microscopy and fluorescence spectroscopy, and the binding affinity of the anti-tau antibodies for tau was evaluated by enzyme-linked immunosorbent assays. Antibodies used were anti-tau 1-150 ("D-8"), anti-tau 259-266 ("Paired-262"), anti-tau 341-360 ("A-10"), and anti-tau 404-441 ("Tau-46"), which bind to tau's N-terminus, microtubule binding domain (MBD) repeat sequences R1 and R4, and the C-terminus, respectively. The antibodies Paired-262 and A-10, but not D-8 and Tau-46, reduced tau fibrillization and degraded preformed tau aggregates, whereas the IVIG reduced tau aggregation but did not alter preformed aggregates. The binding affinities of the antibodies for the epitope for which they were specific did not appear to be related to their effects on tau aggregation. These results confirm that antibody binding to tau's MBD repeat sequences may inhibit tau aggregation and indicate that such antibodies may also degrade preformed tau aggregates. In the presence of anti-tau antibodies, the resulting tau morphologies were antigen-dependent. The results also suggested the possibility of different pathways regulating antibody-mediated inhibition of tau aggregation and antibody-mediated degradation of preformed tau aggregates.

  5. Tau Lorentz Structure with Polarization at SLD

    SciTech Connect

    Abe, K

    2004-01-29

    We present a measurement of the tau neutrino helicity (h{sub {nu}{sub {tau}}}) and the Michel parameters ({rho}, {zeta} and {delta}) by analyzing the {tau} decays {tau} {yields} {pi}(K){nu}{sub {tau}}, {tau} {yields} e{bar {nu}}{sub e}{nu}{sub {tau}} and {tau} {yields} {mu}{bar {nu}}{sub {mu}} in e{sup +}e{sup -} {yields} Z{sup 0} {yields} {tau}{sup +}{tau}{sup -}. The analysis uses the 1993-1995 SLD data sample of 4316 {tau}-pair events produced with highly polarized electrons. We obtain preliminary results of h{sub {nu}{sub {tau}}} = -0.81 {+-} 0.18 {+-} 0.03, {rho} = 0.71 {+-} 0.09 {+-} 0.04, {zeta} = 1.03 {+-} 0.36 {+-} 0.05 and {zeta}{delta} = 0.84 {+-} 0.27 {+-} 0.05.

  6. Tau identification at the Tevatron

    SciTech Connect

    Levy, Stephen; /Chicago U., EFI

    2005-07-01

    Methods for reconstructing and identifying the hadronic decays of tau leptons with the CDF and D0 detectors at the Fermilab Tevatron collider in Run II are described. Precision electroweak measurements of W and Z gauge boson cross sections are presented as well as results of searches for physics beyond the Standard Model with hadronically decaying tau leptons in the final state.

  7. 46 CFR 148.330 - Zinc ashes; zinc dross; zinc residues; zinc skimmings.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Zinc ashes; zinc dross; zinc residues; zinc skimmings... Materials § 148.330 Zinc ashes; zinc dross; zinc residues; zinc skimmings. (a) The shipper must inform the cognizant Coast Guard Captain of the Port in advance of any cargo transfer operations involving zinc...

  8. 46 CFR 148.330 - Zinc ashes; zinc dross; zinc residues; zinc skimmings.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Zinc ashes; zinc dross; zinc residues; zinc skimmings... Materials § 148.330 Zinc ashes; zinc dross; zinc residues; zinc skimmings. (a) The shipper must inform the cognizant Coast Guard Captain of the Port in advance of any cargo transfer operations involving zinc...

  9. 46 CFR 148.330 - Zinc ashes; zinc dross; zinc residues; zinc skimmings.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Zinc ashes; zinc dross; zinc residues; zinc skimmings... Materials § 148.330 Zinc ashes; zinc dross; zinc residues; zinc skimmings. (a) The shipper must inform the cognizant Coast Guard Captain of the Port in advance of any cargo transfer operations involving zinc...

  10. Effects of School Choice on the Margin: The Cream Is Already Skimmed

    ERIC Educational Resources Information Center

    Walsh, Patrick

    2009-01-01

    Critics of school choice argue that cream-skimming will worsen outcomes for those left behind in public schools. Since "high ability" families may have already sorted themselves out of the schools in question, this paper will examine whether existing within-school heterogeneity leaves any scope for cream-skimming to operate. It asks, "given the…

  11. Text Skimming: The Process and Effectiveness of Foraging through Text under Time Pressure

    ERIC Educational Resources Information Center

    Duggan, Geoffrey B.; Payne, Stephen J.

    2009-01-01

    Is Skim reading effective? How do readers allocate their attention selectively? The authors report 3 experiments that use expository texts and allow readers only enough time to read half of each document. Experiment 1 found that, relative to reading half the text, skimming improved memory for important ideas from a text but did not improve memory…

  12. Text Skimming: The Process and Effectiveness of Foraging through Text under Time Pressure

    ERIC Educational Resources Information Center

    Duggan, Geoffrey B.; Payne, Stephen J.

    2009-01-01

    Is Skim reading effective? How do readers allocate their attention selectively? The authors report 3 experiments that use expository texts and allow readers only enough time to read half of each document. Experiment 1 found that, relative to reading half the text, skimming improved memory for important ideas from a text but did not improve memory…

  13. Effects of School Choice on the Margin: The Cream Is Already Skimmed

    ERIC Educational Resources Information Center

    Walsh, Patrick

    2009-01-01

    Critics of school choice argue that cream-skimming will worsen outcomes for those left behind in public schools. Since "high ability" families may have already sorted themselves out of the schools in question, this paper will examine whether existing within-school heterogeneity leaves any scope for cream-skimming to operate. It asks, "given the…

  14. CP violation in hadronic {tau} decays

    SciTech Connect

    Datta, Alakabha; Kiers, Ken; London, David; Szynkman, Alejandro; O'Donnell, Patrick J.

    2007-04-01

    We reexamine CP violation in the {delta}S=0 decays {tau}{yields}N{pi}{nu}{sub {tau}} (N=2,3,4). We assume that the new physics (NP) is a charged Higgs boson. We show that there is no NP contribution to {tau}{yields}{pi}{pi}{nu}{sub {tau}}, which means that no CP violation is expected in this decay. On the other hand, NP can contribute to {tau}{yields}N{pi}{nu}{sub {tau}} (N=3,4). These are dominated by the intermediate resonant decays {tau}{yields}{omega}{pi}{nu}{sub {tau}}, {tau}{yields}{rho}{pi}{nu}{sub {tau}}, and {tau}{yields}a{sub 1}{pi}{nu}{sub {tau}}. We show that the only sizeable CP-violating effects which are possible are in {tau}{yields}a{sub 1}{pi}{nu}{sub {tau}}{yields}4{pi}{nu}{sub {tau}} (polarization-dependent rate asymmetry) and {tau}{yields}{omega}{pi}{nu}{sub {tau}} (triple-product asymmetry)

  15. Ultra-high pressure homogenization-induced changes in skim milk: impact on acid coagulation properties.

    PubMed

    Serra, Mar; Trujillo, Antonio J; Jaramillo, Pamela D; Guamis, Buenaventura; Ferragut, Victoria

    2008-02-01

    The effects of ultra-high pressure homogenization (UHPH) on skim milk yogurt making properties were investigated. UHPH-treated milk was compared with conventionally homogenised (15 MPa) heat-treated skim milk (90 degrees C for 90 s), and to skim milk treated under the same thermal conditions but fortified with 3% skim milk powder. Results of the present study showed that UHPH is capable of reducing skim milk particle size which leads to the formation of finer dispersions than those obtained by conventional homogenisation combined with heat treatment. In addition, results involving coagulation properties and yogurt characteristics reflected that, when increasing UHPH pressure conditions some parameters such as density of the gel, aggregation rate and water retention are improved.

  16. Anti-tau antibody administration increases plasma tau in transgenic mice and patients with tauopathy.

    PubMed

    Yanamandra, Kiran; Patel, Tirth K; Jiang, Hong; Schindler, Suzanne; Ulrich, Jason D; Boxer, Adam L; Miller, Bruce L; Kerwin, Diana R; Gallardo, Gilbert; Stewart, Floy; Finn, Mary Beth; Cairns, Nigel J; Verghese, Philip B; Fogelman, Ilana; West, Tim; Braunstein, Joel; Robinson, Grace; Keyser, Jennifer; Roh, Joseph; Knapik, Stephanie S; Hu, Yan; Holtzman, David M

    2017-04-19

    Tauopathies are a group of disorders in which the cytosolic protein tau aggregates and accumulates in cells within the brain, resulting in neurodegeneration. A promising treatment being explored for tauopathies is passive immunization with anti-tau antibodies. We previously found that administration of an anti-tau antibody to human tau transgenic mice increased the concentration of plasma tau. We further explored the effects of administering an anti-tau antibody on plasma tau. After peripheral administration of an anti-tau antibody to human patients with tauopathy and to mice expressing human tau in the central nervous system, there was a dose-dependent increase in plasma tau. In mouse plasma, we found that tau had a short half-life of 8 min that increased to more than 3 hours after administration of anti-tau antibody. As tau transgenic mice accumulated insoluble tau in the brain, brain soluble and interstitial fluid tau decreased. Administration of anti-tau antibody to tau transgenic mice that had decreased brain soluble tau and interstitial fluid tau resulted in an increase in plasma tau, but this increase was less than that observed in tau transgenic mice without these brain changes. Tau transgenic mice subjected to acute neuronal injury using 3-nitropropionic acid showed increased interstitial fluid tau and plasma tau. These data suggest that peripheral administration of an anti-tau antibody results in increased plasma tau, which correlates with the concentration of extracellular and soluble tau in the brain. Copyright © 2017, American Association for the Advancement of Science.

  17. Photometric and spectroscopic monitoring of AA Tau, DN Tau, UX Tau A, T Tau, RY Tau, Lk Ca 4, and Lk Ca 7

    NASA Technical Reports Server (NTRS)

    Vrba, F. J.; Chugainov, P. F.; Weaver, W. B.; Stauffer, J. S.

    1993-01-01

    We report the results of a UBVRI photometric monitoring campaign for three classical T Tauri stars (AA Tau, DN Tau, and UX Tau A) and two weak emission line T Tauri stars (Lk Ca 4 and Lk Ca 7). Observations were obtained at three sites during a core observing period spanning UT 1985 October 14 through UT 1985 December 25, with additional observations continuing until UT 1986 April 6. Concurrent spectrophotometric observations were obtained for all main program stars except Lk Ca 7 and additionally for T Tau, RW Aur, and RY Tau. Periodic photometric variability, assumed to be the stars' rotation periods, were found for AA Tau, DN Tau, Lk Ca 4, and Lk Ca 7, respectively, as 8.2, 6.3, 3.4, and 5.7 days. Several U-filter flares were observed for Lk Ca 4 and Lk Ca 7, which are strongly concentrated toward phases of minimum light. Correlations are found between H-alpha line strengths and V magnitudes for AA Tau and RY Tau. An analysis of absolute color variations of classical T Tauri stars confirms that hot spots are the predominant cause of these stars' variability. Our overall results are consistent with earlier findings that long-lived cool spots are responsible for most of the variability found for weak-emission T Tauri stars, while temporal hot spots are primarily responsible for the observed variability found in classical T Tauri stars.

  18. Photometric and spectroscopic monitoring of AA Tau, DN Tau, UX Tau A, T Tau, RY Tau, Lk Ca 4, and Lk Ca 7

    NASA Technical Reports Server (NTRS)

    Vrba, F. J.; Chugainov, P. F.; Weaver, W. B.; Stauffer, J. S.

    1993-01-01

    We report the results of a UBVRI photometric monitoring campaign for three classical T Tauri stars (AA Tau, DN Tau, and UX Tau A) and two weak emission line T Tauri stars (Lk Ca 4 and Lk Ca 7). Observations were obtained at three sites during a core observing period spanning UT 1985 October 14 through UT 1985 December 25, with additional observations continuing until UT 1986 April 6. Concurrent spectrophotometric observations were obtained for all main program stars except Lk Ca 7 and additionally for T Tau, RW Aur, and RY Tau. Periodic photometric variability, assumed to be the stars' rotation periods, were found for AA Tau, DN Tau, Lk Ca 4, and Lk Ca 7, respectively, as 8.2, 6.3, 3.4, and 5.7 days. Several U-filter flares were observed for Lk Ca 4 and Lk Ca 7, which are strongly concentrated toward phases of minimum light. Correlations are found between H-alpha line strengths and V magnitudes for AA Tau and RY Tau. An analysis of absolute color variations of classical T Tauri stars confirms that hot spots are the predominant cause of these stars' variability. Our overall results are consistent with earlier findings that long-lived cool spots are responsible for most of the variability found for weak-emission T Tauri stars, while temporal hot spots are primarily responsible for the observed variability found in classical T Tauri stars.

  19. Unique pathological tau conformers from Alzheimer’s brains transmit tau pathology in nontransgenic mice

    PubMed Central

    Changolkar, Lakshmi; Stieber, Anna; Iba, Michiyo; McBride, Jennifer D.

    2016-01-01

    Filamentous tau aggregates are hallmark lesions in numerous neurodegenerative diseases, including Alzheimer’s disease (AD). Cell culture and animal studies showed that tau fibrils can undergo cell-to-cell transmission and seed aggregation of soluble tau, but this phenomenon was only robustly demonstrated in models overexpressing tau. In this study, we found that intracerebral inoculation of tau fibrils purified from AD brains (AD-tau), but not synthetic tau fibrils, resulted in the formation of abundant tau inclusions in anatomically connected brain regions in nontransgenic mice. Recombinant human tau seeded by AD-tau revealed unique conformational features that are distinct from synthetic tau fibrils, which could underlie the differential potency in seeding physiological levels of tau to aggregate. Therefore, our study establishes a mouse model of sporadic tauopathies and points to important differences between tau fibrils that are generated artificially and authentic ones that develop in AD brains. PMID:27810929

  20. Unique pathological tau conformers from Alzheimer's brains transmit tau pathology in nontransgenic mice.

    PubMed

    Guo, Jing L; Narasimhan, Sneha; Changolkar, Lakshmi; He, Zhuohao; Stieber, Anna; Zhang, Bin; Gathagan, Ronald J; Iba, Michiyo; McBride, Jennifer D; Trojanowski, John Q; Lee, Virginia M Y

    2016-11-14

    Filamentous tau aggregates are hallmark lesions in numerous neurodegenerative diseases, including Alzheimer's disease (AD). Cell culture and animal studies showed that tau fibrils can undergo cell-to-cell transmission and seed aggregation of soluble tau, but this phenomenon was only robustly demonstrated in models overexpressing tau. In this study, we found that intracerebral inoculation of tau fibrils purified from AD brains (AD-tau), but not synthetic tau fibrils, resulted in the formation of abundant tau inclusions in anatomically connected brain regions in nontransgenic mice. Recombinant human tau seeded by AD-tau revealed unique conformational features that are distinct from synthetic tau fibrils, which could underlie the differential potency in seeding physiological levels of tau to aggregate. Therefore, our study establishes a mouse model of sporadic tauopathies and points to important differences between tau fibrils that are generated artificially and authentic ones that develop in AD brains. © 2016 Guo et al.

  1. Therapeutic strategies for tau mediated neurodegeneration

    PubMed Central

    Yoshiyama, Yasumasa; Lee, Virginia M Y; Trojanowski, John Q

    2014-01-01

    Based on the amyloid hypothesis, controlling β-amyloid protein (Aβ) accumulation is supposed to suppress downstream pathological events, tau accumulation, neurodegeneration and cognitive decline. However, in recent clinical trials, Aβ removal or reducing Aβ production has shown limited efficacy. Moreover, while active immunisation with Aβ resulted in the clearance of Aβ, it did not prevent tau pathology or neurodegeneration. This prompts the concern that it might be too late to employ Aβ targeting therapies once tau mediated neurodegeneration has occurred. Therefore, it is timely and very important to develop tau directed therapies. The pathomechanisms of tau mediated neurodegeneration are unclear but hyperphosphorylation, oligomerisation, fibrillisation and propagation of tau pathology have been proposed as the likely pathological processes that induce loss of function or gain of toxic function of tau, causing neurodegeneration. Here we review the strategies for tau directed treatments based on recent progress in research on tau and our understanding of the pathomechanisms of tau mediated neurodegeneration. PMID:23085937

  2. Hadronic Tau Decays at BaBar

    SciTech Connect

    Nugent, I.M.; /Victoria U.

    2007-10-25

    Precision measurements of the exclusive branching fraction {tau}{sup -} {yields} K{sup -}{pi}{sup 0}{nu}{sub {tau}} and {tau}{sup -} {yields} h{sup -}h{sup -}h{sup +}{nu}{sub {tau}}, where the h represent either a pion or a kaon, from the BABAR Experiment are presented. The branching fraction for {tau}{sup -} {yields} K{sup -}K{sup -}K{sup +}{nu}{sub {tau}} is the first resonant plus non-resonant measurement of this mode and the branching fraction {tau}{sup -} {yields} {phi}{pi}{sup -}{nu}{sub {tau}} is also a first measurement. In addition we present the new measurement of the branching fraction of {tau}{sup -} {yields} {phi}K{sup -}{nu}{sub {tau}}.

  3. Theory of {tau} mesonic decays

    SciTech Connect

    Li, B.A.

    1997-02-01

    Studies of {tau} mesonic decays are presented. A mechanism for the axial-vector current at low energies is proposed. The VMD is used to treat the vector current. All the meson vertices of both normal parity and abnormal parity (Wess-Zumino-Witten anomaly) are obtained from an effective chiral theory of mesons. a{sub 1} dominance is found in the decay modes of the {tau} lepton: 3{pi}, f(1285){pi}. Both the {rho} and the a{sub 1} meson contribute to the decay {tau}{r_arrow}K{sup {asterisk}}K{nu}; it is found that the vector current is dominant. CVC is tested by studying e{sup +}e{sup {minus}}{r_arrow}{pi}{sup +}{pi}{sup {minus}}. The branching ratios of {tau}{r_arrow}{omega}{pi}{nu} and K{bar K}{nu} are calculated. In terms of a similar mechanism the {Delta}s=1 decay modes of the {tau} lepton are studied and K{sub a} dominance is found in {tau}{r_arrow}K{sup {asterisk}}{pi}{nu} and K{sup {asterisk}}{eta}{nu}. The suppression of {tau}{r_arrow}K{rho}{nu} is revealed. The branching ratio of {tau}{r_arrow}{eta}K{nu} is computed. As a test of this theory, the form factors of {pi}{r_arrow}e{gamma}{nu} and K{r_arrow}e{gamma}{nu} are determined. The theoretical results agree with data reasonably well. {copyright} {ital 1997} {ital The American Physical Society}

  4. Closing the tau loop: the missing tau mutation.

    PubMed

    McCarthy, Allan; Lonergan, Roisin; Olszewska, Diana A; O'Dowd, Sean; Cummins, Gemma; Magennis, Brian; Fallon, Emer M; Pender, Niall; Huey, Edward D; Cosentino, Stephanie; O'Rourke, Killian; Kelly, Brendan D; O'Connell, Martin; Delon, Isabelle; Farrell, Michael; Spillantini, Maria Grazia; Rowland, Lewis P; Fahn, Stanley; Craig, Peter; Hutton, Michael; Lynch, Tim

    2015-10-01

    Frontotemporal lobar degeneration comprises a group of disorders characterized by behavioural, executive, language impairment and sometimes features of parkinsonism and motor neuron disease. In 1994 we described an Irish-American family with frontotemporal dementia linked to chromosome 17 associated with extensive tau pathology. We named this disinhibition-dementia-parkinsonism-amyotrophy complex. We subsequently identified mutations in the MAPT gene. Eleven MAPT gene splice site stem loop mutations were identified over time except for 5' splice site of exon 10. We recently identified another Irish family with autosomal dominant early amnesia and behavioural change or parkinsonism associated with the 'missing' +15 mutation at the intronic boundary of exon 10. We performed a clinical, neuropsychological and neuroimaging study on the proband and four siblings, including two affected siblings. We sequenced MAPT and performed segregation analysis. We looked for a biological effect of the tau variant by performing real-time polymerase chain reaction analysis of RNA extracted from human embryonic kidney cells transfected with exon trapping constructs. We found a c.915+15A>C exon 10/intron 10 stem loop mutation in all affected subjects but not in the unaffected. The c.915+15A>C variant caused a shift in tau splicing pattern to a predominantly exon 10+ pattern presumably resulting in predominant 4 repeat tau and little 3 repeat tau. This strongly suggests that the c.915+15A>C variant is a mutation and that it causes frontotemporal dementia linked to chromosome 17 in this pedigree by shifting tau transcription and translation to +4 repeat tau. Tau (MAPT) screening should be considered in families where amnesia or atypical parkinsonism coexists with behavioural disturbance early in the disease process. We describe the final missing stem loop tau mutation predicted 15 years ago. Mutations have now been identified at all predicted sites within the 'stem' when the stem

  5. Closing the tau loop: the missing tau mutation

    PubMed Central

    McCarthy, Allan; Lonergan, Roisin; Olszewska, Diana A.; O’Dowd, Sean; Cummins, Gemma; Magennis, Brian; Fallon, Emer M.; Pender, Niall; Huey, Edward D.; Cosentino, Stephanie; O’Rourke, Killian; Kelly, Brendan D.; O’Connell, Martin; Delon, Isabelle; Farrell, Michael; Spillantini, Maria Grazia; Rowland, Lewis P.; Fahn, Stanley; Craig, Peter; Hutton, Michael

    2015-01-01

    Frontotemporal lobar degeneration comprises a group of disorders characterized by behavioural, executive, language impairment and sometimes features of parkinsonism and motor neuron disease. In 1994 we described an Irish-American family with frontotemporal dementia linked to chromosome 17 associated with extensive tau pathology. We named this disinhibition-dementia-parkinsonism-amyotrophy complex. We subsequently identified mutations in the MAPT gene. Eleven MAPT gene splice site stem loop mutations were identified over time except for 5’ splice site of exon 10. We recently identified another Irish family with autosomal dominant early amnesia and behavioural change or parkinsonism associated with the ‘missing’ +15 mutation at the intronic boundary of exon 10. We performed a clinical, neuropsychological and neuroimaging study on the proband and four siblings, including two affected siblings. We sequenced MAPT and performed segregation analysis. We looked for a biological effect of the tau variant by performing real-time polymerase chain reaction analysis of RNA extracted from human embryonic kidney cells transfected with exon trapping constructs. We found a c.915+15A>C exon 10/intron 10 stem loop mutation in all affected subjects but not in the unaffected. The c.915+15A>C variant caused a shift in tau splicing pattern to a predominantly exon 10+ pattern presumably resulting in predominant 4 repeat tau and little 3 repeat tau. This strongly suggests that the c.915+15A>C variant is a mutation and that it causes frontotemporal dementia linked to chromosome 17 in this pedigree by shifting tau transcription and translation to +4 repeat tau. Tau (MAPT) screening should be considered in families where amnesia or atypical parkinsonism coexists with behavioural disturbance early in the disease process. We describe the final missing stem loop tau mutation predicted 15 years ago. Mutations have now been identified at all predicted sites within the ‘stem’ when the

  6. Microsphere skimming in the porcine coronary arteries: Implications for flow quantification.

    PubMed

    Sinclair, Matthew; Lee, Jack; Schuster, Andreas; Chiribiri, Amedeo; van den Wijngaard, Jeroen; van Horssen, Pepijn; Siebes, Maria; Spaan, Jos A E; Nagel, Eike; Smith, Nicolas P

    2015-07-01

    Particle skimming is a phenomenon where particles suspended in fluid flowing through vessels distribute disproportionately to bulk fluid volume at junctions. Microspheres are considered a gold standard of intra-organ perfusion measurements and are used widely in studies of flow distribution and quantification. It has previously been hypothesised that skimming at arterial junctions is responsible for a systematic over-estimation of myocardial perfusion from microspheres at the subendocardium. Our objective is to integrate coronary arterial structure and microsphere distribution, imaged at high resolution, to test the hypothesis of microsphere skimming in a porcine left coronary arterial (LCA) network. A detailed network was reconstructed from cryomicrotome imaging data and a Poiseuille flow model was used to simulate flow. A statistical approach using Clopper-Pearson confidence intervals was applied to determine the prevalence of skimming at bifurcations in the LCA. Results reveal that microsphere skimming is most prevalent at bifurcations in the larger coronary arteries, namely the epicardial and transmural arteries. Bifurcations at which skimming was identified have significantly more asymmetric branching parameters. This finding suggests that when using thin transmural segments to quantify flow from microspheres, a skimming-related deposition bias may result in underestimation of perfusion in the subepicardium, and overestimation in the subendocardium.

  7. A microfiltration process to maximize removal of serum proteins from skim milk before cheese making.

    PubMed

    Nelson, B K; Barbano, D M

    2005-05-01

    Microfiltration (MF) is a membrane process that can separate casein micelles from milk serum proteins (SP), mainly beta-lactoglobulin and alpha-lactalbumin. Our objective was to develop a multistage MF process to remove a high percentage of SP from skim milk while producing a low concentration factor retentate from microfiltration (RMF) with concentrations of soluble minerals, nonprotein nitrogen (NPN), and lactose similar to the original skim milk. The RMF could be blended with cream to standardize milk for traditional Cheddar cheese making. Permeate from ultrafiltration (PUF) obtained from the ultrafiltration (UF) of permeate from MF (PMF) of skim milk was successfully used as a diafiltrant to remove SP from skim milk before cheese making, while maintaining the concentration of lactose, NPN, and nonmicellar calcium. About 95% of the SP originally in skim milk was removed by combining one 3 x MF stage and two 3 x PUF diafiltration stages. The final 3 x RMF can be diluted with PUF to the desired concentration of casein for traditional cheese making. The PMF from the skim milk was concentrated in a UF system to yield an SP concentrate with protein content similar to a whey protein concentrate, but without residuals from cheese making (i.e., rennet, culture, color, and lactic acid) that can produce undesirable functional and sensory characteristics in whey products. Additional processing steps to this 3-stage MF process for SP removal are discussed to produce an MF skim retentate for a continuous cottage cheese manufacturing process.

  8. Extracellular Tau Oligomers Induce Invasion of Endogenous Tau into the Somatodendritic Compartment and Axonal Transport Dysfunction

    PubMed Central

    Swanson, Eric; Breckenridge, Leigham; McMahon, Lloyd; Som, Sreemoyee; McConnell, Ian; Bloom, George S.

    2017-01-01

    Aggregates composed of the microtubule associated protein, tau, are a hallmark of Alzheimer’s disease and non-Alzheimer’s tauopathies. Extracellular tau can induce the accumulation and aggregation of intracellular tau, and tau pathology can be transmitted along neural networks over time. There are six splice variants of central nervous system tau, and various oligomeric and fibrillar forms are associated with neurodegeneration in vivo. The particular extracellular forms of tau capable of transferring tau pathology from neuron to neuron remain ill defined, however, as do the consequences of intracellular tau aggregation on neuronal physiology. The present study was undertaken to compare the effects of extracellular tau monomers, oligomers, and filaments comprising various tau isoforms on the behavior of cultured neurons. We found that 2N4R or 2N3R tau oligomers provoked aggregation of endogenous intracellular tau much more effectively than monomers or fibrils, or of oligomers made from other tau isoforms, and that a mixture of all six isoforms most potently provoked intracellular tau accumulation. These effects were associated with invasion of tau into the somatodendritic compartment. Finally, we observed that 2N4R oligomers perturbed fast axonal transport of membranous organelles along microtubules. Intracellular tau accumulation was often accompanied by increases in the run length, run time and instantaneous velocity of membranous cargo. This work indicates that extracellular tau oligomers can disrupt normal neuronal homeostasis by triggering axonal tau accumulation and loss of the polarized distribution of tau, and by impairing fast axonal transport. PMID:28482642

  9. Extracellular Tau Oligomers Induce Invasion of Endogenous Tau into the Somatodendritic Compartment and Axonal Transport Dysfunction.

    PubMed

    Swanson, Eric; Breckenridge, Leigham; McMahon, Lloyd; Som, Sreemoyee; McConnell, Ian; Bloom, George S

    2017-01-01

    Aggregates composed of the microtubule associated protein, tau, are a hallmark of Alzheimer's disease and non-Alzheimer's tauopathies. Extracellular tau can induce the accumulation and aggregation of intracellular tau, and tau pathology can be transmitted along neural networks over time. There are six splice variants of central nervous system tau, and various oligomeric and fibrillar forms are associated with neurodegeneration in vivo. The particular extracellular forms of tau capable of transferring tau pathology from neuron to neuron remain ill defined, however, as do the consequences of intracellular tau aggregation on neuronal physiology. The present study was undertaken to compare the effects of extracellular tau monomers, oligomers, and filaments comprising various tau isoforms on the behavior of cultured neurons. We found that 2N4R or 2N3R tau oligomers provoked aggregation of endogenous intracellular tau much more effectively than monomers or fibrils, or of oligomers made from other tau isoforms, and that a mixture of all six isoforms most potently provoked intracellular tau accumulation. These effects were associated with invasion of tau into the somatodendritic compartment. Finally, we observed that 2N4R oligomers perturbed fast axonal transport of membranous organelles along microtubules. Intracellular tau accumulation was often accompanied by increases in the run length, run time and instantaneous velocity of membranous cargo. This work indicates that extracellular tau oligomers can disrupt normal neuronal homeostasis by triggering axonal tau accumulation and loss of the polarized distribution of tau, and by impairing fast axonal transport.

  10. Effect of fractional blood flow on plasma skimming in the microvasculature

    NASA Astrophysics Data System (ADS)

    Yang, Jiho; Yoo, Sung Sic; Lee, Tae-Rin

    2017-04-01

    Although redistribution of red blood cells at bifurcated vessels is highly dependent on flow rate, it is still challenging to quantitatively express the dependence of flow rate in plasma skimming due to nonlinear cellular interactions. We suggest a plasma skimming model that can involve the effect of fractional blood flow at each bifurcation point. To validate the model, it is compared with in vivo data at single bifurcation points, as well as microvascular network systems. In the simulation results, the exponential decay of the plasma skimming parameter M along fractional flow rate shows the best performance in both cases.

  11. Skim Milk Enhances the Preservation of Thawed -80°C Bacterial Stocks

    PubMed Central

    Cody, William L.; Wilson, James W.; Hendrixson, David R.; McIver, Kevin S.; Hagman, Kayla E.; Ott, C.M.; Nickerson, Cheryl A.; Schurr, Michael J.

    2008-01-01

    The results from bacterial strain recovery efforts following hurricanes Katrina and Rita are reported. Over 90% of strains frozen in 10% skim milk were recovered whereas various recovery rates were observed for glycerol-stored stocks (56% and 94% of E. coli, depending upon the laboratory). These observations led to a viability comparison of Streptococcus pyogenes, Campylobacter jejuni, Borrelia burgdorferi, Salmonella enterica subsp. Typhimurium, Pseudomonas aeruginosa and Escherichia coli strains stored in glycerol or skim milk. In all bacteria examined, 10% skim milk resulted in significantly longer viability after thawing than 15% glycerol solutions currently used in most laboratories. PMID:18573555

  12. Interaction of Tau with Fe65 links tau to APP.

    PubMed

    Barbato, Christian; Canu, Nadia; Zambrano, Nicola; Serafino, Annalucia; Minopoli, Giuseppina; Ciotti, Maria Teresa; Amadoro, Giuseppina; Russo, Tommaso; Calissano, Pietro

    2005-03-01

    The beta-amyloid precursor protein APP and the microtubule-associated protein Tau play a crucial role in the pathogenesis of Alzheimer's disease (AD). However, the possible molecular events linking these two proteins are still unknown. Here, we show that Fe65, one of the ligands of the APP cytodomain, is associated with Tau in vivo and in vitro, as demonstrated by co-immunoprecipitation, co-localization, and FRET experiments. Deletion studies indicated that the N-terminal domain of Tau and the PTB1 domain of Fe65 are required for this association. This interaction is regulated by the phosphorylation of Tau at selected sites, by glycogen synthase kinase-3beta (GSK3beta) and cyclin-dependent kinase 5 (Cdk5), and requires an intact microtubule network. Furthermore, laser scanner microscopy and co-immunoprecipitation experiments provide preliminary evidence of possible complex(es) involving Tau, Fe65, APP. These findings open new perspectives for the study of the possible crosstalk between these proteins in the pathogenesis of AD.

  13. Atmospheric Tau Neutrino Appearance Analysis with IceCube/DeepCore

    NASA Astrophysics Data System (ADS)

    Huang, Feifei; IceCube Collaboration

    2017-01-01

    DeepCore is the low-energy subarray of the IceCube Neutrino Observatory at the South Pole, and provides sensitivity in the neutrino energy range above roughly 10 GeV, where Earth-crossing neutrinos experience oscillations. These neutrinos are muon and electron neutrinos produced in Earth's atmosphere via decays of particles from interactions between cosmic rays and the atmosphere. While tau neutrino interactions in DeepCore cannot be distinguished from those of electron neutrinos at these energies, a statistical separation of these two event classes can be made based on the reconstructed energy and zenith distribution. Therefore, tau neutrino appearance, mainly from muon neutrino to tau neutrino oscillations, can be measured with high significance using IceCube/DeepCore data. We present preliminary results of a tau neutrino appearance analysis using several years of IceCube/DeepCore data.

  14. Accelerated Human Mutant Tau Aggregation by Knocking Out Murine Tau in a Transgenic Mouse Model

    PubMed Central

    Ando, Kunie; Leroy, Karelle; Héraud, Céline; Yilmaz, Zehra; Authelet, Michèle; Suain, Valèrie; De Decker, Robert; Brion, Jean-Pierre

    2011-01-01

    Many models of human tauopathies have been generated in mice by expression of a human mutant tau with maintained expression of mouse endogenous tau. Because murine tau might interfere with the toxic effects of human mutant tau, we generated a model in which a pathogenic human tau protein is expressed in the absence of wild-type tau protein, with the aim of facilitating the study of the pathogenic role of the mutant tau and to reproduce more faithfully a human tauopathy. The Tg30 line is a tau transgenic mouse model overexpressing human 1N4R double-mutant tau (P301S and G272V) that develops Alzheimer's disease-like neurofibrillary tangles in an age-dependent manner. By crossing Tg30 mice with mice invalidated for their endogenous tau gene, we obtained Tg30xtau−/− mice that express only exogenous human double-mutant 1N4R tau. Although Tg30xtau−/− mice express less tau protein compared with Tg30, they exhibit signs of decreased survival, increased proportion of sarkosyl-insoluble tau in the brain and in the spinal cord, increased number of Gallyas-positive neurofibrillary tangles in the hippocampus, increased number of inclusions in the spinal cord, and a more severe motor phenotype. Deletion of murine tau accelerated tau aggregation during aging of this mutant tau transgenic model, suggesting that murine tau could interfere with the development of tau pathology in transgenic models of human tauopathies. PMID:21281813

  15. Tau Induces Cooperative Taxol Binding to Microtubules

    NASA Astrophysics Data System (ADS)

    Ross, Jennifer; Santangelo, Christian; Victoria, Makrides; Fygenson, Deborah

    2004-03-01

    Taxol and tau are two ligands which stabilize the microtubule (MT) lattice. Taxol is an anti-mitotic drug that binds β tubulin in the MT interior. Tau is a MT-associated protein that binds both α and β tubulin on the MT exterior. Both taxol and tau reduce MT dynamics and promote tubulin polymerization. Tau alone also acts as a buttress to bundle, stiffen, and space MTs. A structural study recently suggested that taxol and tau may interact by binding to the same site. Using fluorescence recovery after photobleaching, we find that tau induces taxol to bind MTs cooperatively depending on the tau concentration. We develop a model that correctly fits the data in the absence of tau and yields a measure of taxol cooperativity when tau is present.

  16. A Quantitative Analysis of Brain Soluble Tau and the Tau Secretion Factor.

    PubMed

    Han, Pengcheng; Serrano, Geidy; Beach, Thomas G; Caselli, Richard J; Yin, Junxiang; Zhuang, Ningning; Shi, Jiong

    2017-01-09

    Neurofibrillary tangles (NFTs) represent products of insoluble tau protein in the brains of patients with Alzheimer disease (AD). The cerebrospinal fluid (CSF) tau level is a biomarker in AD diagnosis. The soluble portion of tau protein in brain parenchyma is presumably the source for CSF tau but this has not previously been quantified. We measured CSF tau and soluble brain tau at autopsy in temporal and frontal brain tissue samples from 7 cognitive normal, 12 mild cognitively impaired, and 19 AD subjects. Based on the measured brain soluble tau, we calculated the whole brain tau load and estimated tau secretion factor. Our results suggest that the increase in NFT in AD is likely attributable to post-translational processes; the increase in CSF tau in AD patients is due to an accelerated carrier-based secretion. Moreover, cognitive dysfunction assessed by final Mini-Mental State Examination scores correlated with the secretion factor but not with the soluble tau.

  17. Heat stability of reconstituted, protein-standardized skim milk powders.

    PubMed

    Sikand, V; Tong, P S; Walker, J

    2010-12-01

    We determined the effects of standardization material, protein content, and pH on the heat stability of reconstituted milk made from low-heat (LH) and medium-heat (MH) nonfat dry milk (NDM). Low-heat and MH NDM were standardized downward from 35.5% to 34, 32, and 30% protein by adding either edible lactose powder (ELP) or permeate powder (PP) from skim milk ultrafiltration. These powders were called standardized skim milk powders (SSMP). The LH and MH NDM and SSMP were reconstituted to 9% total solids. Furthermore, subsamples of reconstituted NDM and SSMP samples were set aside to measure heat stability at native (unadjusted) pH, and the rest were adjusted to pH 6.3 to 7.0. Heat stability is defined as heat coagulation time at 140°C of the reconstituted LH or MH NDM and SSMP samples. The entire experiment was replicated 3 times at unadjusted pH values and 2 times at adjusted pH values. At an unadjusted pH, powder type, standardization material, and protein content influenced the heat stability of the samples. Heat stability for reconstituted LH NDM and SSMP was higher than reconstituted MH NDM and SSMP. Generally, decreased heat stability was observed in reconstituted LH or MH SSMP as protein content was decreased by standardization. However, adding ELP to MH SSMP did not significantly change its heat stability. When pH was adjusted to values between 6.3 and 7.0, powder type, standardization material, and pH had a significant effect on heat stability, whereas protein content did not. Maximum heat stability was noted at pH 6.7 for both reconstituted LH NDM and SSMP samples, and at pH 6.6 for both reconstituted MH NDM and SSMP samples. Furthermore, for samples with adjusted pH, higher heat stability was observed for reconstituted LH SSMP containing PP compared with reconstituted milk from LH SSMP containing ELP. However, no statistical difference was observed in the heat stability of reconstituted milk from MH NDM and MH SSMP samples. We conclude that powder type

  18. Characterization of tau fibrillization in vitro.

    PubMed

    Xu, Shaohua; Brunden, Kurt R; Trojanowski, John Q; Lee, Virginia M-Y

    2010-03-01

    The assembly of tau proteins into paired helical filaments, the building blocks of neurofibrillary tangles, is linked to neurodegeneration in Alzheimer's disease and related tauopathies. A greater understanding of this assembly process could identify targets for the discovery of drugs to treat Alzheimer's disease and related disorders. By using recombinant human tau, we have delineated events leading to the conversion of normal soluble tau into tau fibrils. Atomic force microscopy and transmission electron microscopy methodologies were used to determine the structure of tau assemblies that formed when soluble tau was incubated with heparin for increasing lengths of time. Tau initially oligomerizes into spherical nucleation units of 18- to 21-nm diameter that appear to assemble linearly into nascent fibrils. Among the earliest tau fibrils are species that resemble a string of beads formed by linearly aligned spheres that with time seem to coalesce to form straight and twisted ribbon-like filaments, as well as paired helical filaments similar to those found in human tauopathies. An analysis of fibril cross sections at later incubation times revealed three fundamental axial structural features. By monitoring tau fibrillization, we showed that different tau filament morphologies coexist. Temporal changes in the predominant tau structural species suggest that tau fibrillization involves the generation of structural intermediates, resulting in the formation of tau fibrils with verisimilitude to their authentic human counterparts. 2010 The Alzheimer's Association. All rights reserved.

  19. The role of tau in neurodegeneration

    PubMed Central

    Gendron, Tania F; Petrucelli, Leonard

    2009-01-01

    Since the identification of tau as the main component of neurofibrillary tangles in Alzheimer's disease and related tauopathies, and the discovery that mutations in the tau gene cause frontotemporal dementia, much effort has been directed towards determining how the aggregation of tau into fibrillar inclusions causes neuronal death. As evidence emerges that tau-mediated neuronal death can occur even in the absence of tangle formation, a growing number of studies are focusing on understanding how abnormalities in tau (e.g. aberrant phosphorylation, glycosylation or truncation) confer toxicity. Though data obtained from experimental models of tauopathies strongly support the involvement of pathologically modified tau and tau aggregates in neurodegeneration, the exact neurotoxic species remain unclear, as do the mechanism(s) by which they cause neuronal death. Nonetheless, it is believed that tau-mediated neurodegeneration is likely to result from a combination of toxic gains of function as well as from the loss of normal tau function. To truly appreciate the detrimental consequences of aberrant tau function, a better understanding of all functions carried out by tau, including but not limited to the role of tau in microtubule assembly and stabilization, is required. This review will summarize what is currently known regarding the involvement of tau in the initiation and development of neurodegeneration in tauopathies, and will also highlight some of the remaining questions in need of further investigation. PMID:19284597

  20. Skimming the surface with Burgess Shale arthropod locomotion

    PubMed Central

    Minter, Nicholas J.; Mángano, M. Gabriela; Caron, Jean-Bernard

    2012-01-01

    The first arthropod trackways are described from the Middle Cambrian Burgess Shale Formation of Canada. Trace fossils, including trackways, provide a rich source of biological and ecological information, including direct evidence of behaviour not commonly available from body fossils alone. The discovery of large arthropod trackways is unique for Burgess Shale-type deposits. Trackway dimensions and the requisite number of limbs are matched with the body plan of a tegopeltid arthropod. Tegopelte, one of the rarest Burgess Shale animals, is over twice the size of all other benthic arthropods known from this locality, and only its sister taxon, Saperion, from the Lower Cambrian Chengjiang biota of China, approaches a similar size. Biomechanical trackway analysis demonstrates that tegopeltids were capable of rapidly skimming across the seafloor and, in conjunction with the identification of gut diverticulae in Tegopelte, supports previous hypotheses on the locomotory capabilities and carnivorous mode of life of such arthropods. The trackways occur in the oldest part (Kicking Horse Shale Member) of the Burgess Shale Formation, which is also known for its scarce assemblage of soft-bodied organisms, and indicate at least intermittent oxygenated bottom waters and low sedimentation rates. PMID:22072605

  1. Skimming the surface with Burgess Shale arthropod locomotion.

    PubMed

    Minter, Nicholas J; Mángano, M Gabriela; Caron, Jean-Bernard

    2012-04-22

    The first arthropod trackways are described from the Middle Cambrian Burgess Shale Formation of Canada. Trace fossils, including trackways, provide a rich source of biological and ecological information, including direct evidence of behaviour not commonly available from body fossils alone. The discovery of large arthropod trackways is unique for Burgess Shale-type deposits. Trackway dimensions and the requisite number of limbs are matched with the body plan of a tegopeltid arthropod. Tegopelte, one of the rarest Burgess Shale animals, is over twice the size of all other benthic arthropods known from this locality, and only its sister taxon, Saperion, from the Lower Cambrian Chengjiang biota of China, approaches a similar size. Biomechanical trackway analysis demonstrates that tegopeltids were capable of rapidly skimming across the seafloor and, in conjunction with the identification of gut diverticulae in Tegopelte, supports previous hypotheses on the locomotory capabilities and carnivorous mode of life of such arthropods. The trackways occur in the oldest part (Kicking Horse Shale Member) of the Burgess Shale Formation, which is also known for its scarce assemblage of soft-bodied organisms, and indicate at least intermittent oxygenated bottom waters and low sedimentation rates.

  2. Local surface skimming longitudinal wave velocity and residual stress mapping.

    PubMed

    Sathish, Shamachary; Martin, Richard W; Moran, Thomas J

    2004-01-01

    Local variation in surface skimming longitudinal wave (SSLW) velocity has been measured using a scanning acoustic microscope. A very narrow width electrical impulse has been used to excite the transducer of the acoustic lens. This permits the separation of the SSLW signal from the direct reflected signal in the time domain. A simple method of measuring the time delay between the directly reflected signal and the SSLW signal at two defocuses has been utilized for the local measurement of SSLW velocity. The variation in the SSLW velocity measured over an area of the sample is scaled and presented as an image. The method has been implemented to image the variation of the SSLW velocity around a crack tip in a sample of Ti-6Al-4V. Since the SSLW velocity is known to change linearly with the stress, the SSLW velocity image is considered as a representation of the image of stress around the crack tip. Local stress variation in the same region of the crack tip is directly measured using x-ray diffraction. The SSLW velocity image is compared with the x-ray diffraction stress image. The contrast in the two images, spatial resolution, and the penetration depth into the sample of acoustic waves and x rays are discussed.

  3. Tau decays into K* mesons

    NASA Astrophysics Data System (ADS)

    Albrecht, H.; Hamacher, T.; Hofmann, R. P.; Kirchhoff, T.; Mankel, R.; Nau, A.; Nowak, S.; Schröder, H.; Schulz, H. D.; Walter, M.; Wurth, R.; Hast, C.; Kapitza, H.; Kolanoski, H.; Kosche, A.; Lange, A.; Lindner, A.; Schieber, M.; Siegmund, T.; Spaan, B.; Thurn, H.; Töpfer, D.; Wegener, D.; Eckstein, P.; Schubert, K. R.; Schwierz, R.; Waldi, R.; Reim, K.; Wegener, H.; Eckmann, R.; Kuipers, H.; Mai, O.; Mundt, R.; Oest, T.; Reiner, R.; Schmidt-Parzefall, W.; Stiewe, J.; Werner, S.; Ehret, K.; Hofmann, W.; Hüpper, A.; Knöpfle, K. T.; Spengler, J.; Krieger, P.; Macfarlane, D. B.; Saull, P. R. B.; Tzamariudaki, K.; van de Water, R. G.; Yoon, T.-S.; Frankl, C.; Reßing, D.; Schmidtler, M.; Schneider, M.; Weseler, S.; Kernel, G.; Križan, P.; Križnič, E.; Podobnik, T.; Živko, T.; Balagura, V.; Belyaev, I.; Schechelnitsky, S.; Danilov, M.; Doutskoy, A.; Gershtein, Yu.; Golutvin, A.; Korolko, I.; Kostina, G.; Litvintsev, D.; Lubimov, V.; Pakhlov, P.; Semenov, S.; Snizhko, A.; Tichomirov, I.; Zaitsev, Yu.

    1995-06-01

    Using the ARGUS detector at the storage ring DORIS II we have measured τ decays into three charged mesons containing K * mesons. Exploiting the good particle identification capabilities of the detector we have determined the following branching ratios:Brleft( {tau ^ - to overline {K^{*0} } π ^ - v_tau } right) = left( {0.25 ± 0.10 ± 0.05} right)% , B r (τ-→ K *0 K - v τ)= (0.20±0.05±0.04)%, and B r (τ-→ K *- X 0 v τ) =(1.15±0.15-0.18 +0.13)%.

  4. Elevated cerebrospinal fluid tau in Wernicke encephalopathy.

    PubMed

    Frijlink, Daphne W; Tilanus, Joachim J; Roks, Gerwin

    2012-08-08

    Wernicke encephalopathy (WE) commonly presents with oculomotor abnormalities, gait ataxia and confusion. WE can mimic rapidly progressive dementia syndromes, such as Creutzfeldt-Jakob disease (CJD). Cerebrospinal fluid (CSF) tau is frequently used for diagnosis of several dementia subtypes, predominantly CJD and Alzheimer's disease. The combination of very high CSF tau (tau) and normal phosphorylated tau (p-tau) levels is almost exclusively seen in aggressive diseases, such as CJD. The authors present a case of a woman with WE, caused by chronic insufficient dietary intake, with highly elevated CSF tau and normal p-tau. The clinical symptoms and CSF findings raised the suspicion of CJD. However, shortly after immediate treatment with thiamine the patient clinically improved. At follow-up, 2.5 months later, she had made a good recovery. This case of rapidly progressive dementia illustrates that, even in the case of a highly elevated CSF tau, clinicians should be alert for treatable causes such as WE.

  5. The. tau. -lepton and its associated neutrino

    SciTech Connect

    Pich, A. )

    1990-10-10

    This paper discusses the {tau}-lepton and the prospects for future improvements. It is shown how a better understanding of the {tau} properties could be used for testing fundamental aspects of the electroweak and strong interactions.

  6. Vitamin B12 Inhibits Tau Fibrillization via Binding to Cysteine Residues of Tau.

    PubMed

    Rafiee, Saharnaz; Asadollahi, Kazem; Riazi, Gholamhossein; Ahmadian, Shahin; Saboury, Ali Akbar

    2017-09-06

    Two mechanisms underlie the inhibitory/acceleratory action of chemical compounds on tau aggregation including the regulation of cellular kinases and phosphatases activity and direct binding to tau protein. Vitamin B12 is one of the tau polymerization inhibitors, and its deficiency is linked to inactivation of protein phosphatase 2A and subsequently hyperphosphorylation and aggregation of tau protein. Regarding the structure and function of vitamin B12 and tau protein, we assumed that vitamin B12 is also able to directly bind to tau protein. Hence, we investigated the interaction of vitamin B12 with tau protein in vitro using fluorometry and circular dichrosim. Interaction studies was followed by investigation into the effect of vitamin B12 on tau aggregation using ThT fluorescence, circular dichroism, transmission electron microscopy, and SDS-PAGE. The results indicated that vitamin B12 interacts with tau protein and prevents fibrillization of tau protein. Blocking the cysteine residues of tau confirmed the cysteine-mediated binding of vitamin B12 to tau and showed that binding to cysteine is essential for inhibitory effect of vitamin B12 on tau aggregation. SDS-PAGE analysis indicated that vitamin B12 inhibits tau aggregation and that tau oligomers formed in the presence of vitamin B12 are mostly SDS-soluble. We propose that direct binding of vitamin B12 is another mechanism underlying the inhibitory role of vitamin B12 on tau aggregation and neurodegeneration.

  7. Tau Decays at BaBar

    SciTech Connect

    Hast, Carsten; /SLAC

    2009-01-22

    Recent results of tau lepton decay studies based on luminosities between 350 fb{sup -1} and 469 fb{sup -1} collected with the BABAR detector at the PEP-II e{sup +}e{sup -} collider at the SLAC National Accelerator Laboratory are presented. The analyses reported here are Charged Current Lepton Universality and measurements of |V{sub us}| using {tau}{sup -} {yields} e{sup -}{bar {nu}}{sub e}{nu}{sub {tau}}, {mu}{sup -}{bar {nu}}{sub {mu}}{nu}{sub {tau}}, {pi}{sup -} {nu}{sub {tau}}, and K{sup -}{nu}{sub {tau}} decays, as well as searches for Second Class Currents in {tau}{sup -} {yields} {omega}{pi}{sup -}{nu}{sub {tau}} decays, studies of Lepton Flavor Violations, and a tau mass measurement and CPT-Test. If not explicitly mentioned, charge conjugate decay modes are also implied. decays, as well as searches for Second Class Currents in {tau}{sup -} {yields} {omega}{pi}{sup -}{nu}{sub {tau}} decays, studies of Lepton Flavor Violations, and a tau mass measurement and CPT-Test. If not explicitly mentioned, charge conjugate decay modes are also implied.

  8. Tau Trigger at the ATLAS Experiment

    SciTech Connect

    Benslama, K.; Kalinowski, A.; Belanger-Champange, C.; Brenner, R.; Bosman, M.; Casado, P.; Osuna, C.; Perez, E.; Vorwerk, V.; Czyczula, Z.; Dam, M.; Xella, S.; Demers, S.; Farrington, S.; Igonkina, O.; Kanaya, N.; Tsuno, S.; Ptacek, E.; Reinsch, A.; Strom, David M.; Torrence, E.; /Oregon U. /Sydney U. /Lancaster U. /Birmingham U.

    2011-11-09

    Many theoretical models, like the Standard Model or SUSY at large tan({beta}), predict Higgs bosons or new particles which decay more abundantly to final states including tau leptons than to other leptons. At the energy scale of the LHC, the identification of tau leptons, in particular in the hadronic decay mode, will be a challenging task due to an overwhelming QCD background which gives rise to jets of particles that can be hard to distinguish from hadronic tau decays. Equipped with excellent tracking and calorimetry, the ATLAS experiment has developed tau identification tools capable of working at the trigger level. This contribution presents tau trigger algorithms which exploit the main features of hadronic tau decays and describes the current tau trigger commissioning activities. Many of the SM processes being investigated at ATLAS, as well as numerous BSM searches, contain tau leptons in their final states. Being able to trigger effectively on the tau leptons in these events will contribute to the success of the ATLAS experiment. The tau trigger algorithms and monitoring infrastructure are ready for the first data, and are being tested with the data collected with cosmic muons. The development of efficiency measurements methods using QCD and Z {yields} {tau}{tau} events is well advanced.

  9. A Tau-Charm Factory at CEBAF

    SciTech Connect

    Seth, K.K.

    1994-04-01

    It is proposed that a Tau Charm Factory represents a natural extension of CEBAF into higher energy domains. The exciting nature of the physics of charm quarks and tau leptons is briefly reviewed and it is suggested that the concept of a linac-ring collider as a Tau Charm Factory at CEBAF should be seriously studied.

  10. UX Tau A Artist Concept

    NASA Image and Video Library

    2007-11-28

    This artist concept is of the one-million-year-old star system called UX Tau A, approximately 450 light-years away. NASA Spitzer Space Telescope showed a gap in the dusty planet-forming disk swirling around the system central sun-like star.

  11. Prospect for measuring the CP phase in the $h\\tau\\tau$ coupling at the LHC

    SciTech Connect

    Askew, Andrew; Jaiswal, Prerit; Okui, Takemichi; Prosper, Harrison B.; Sato, Nobuo

    2015-04-01

    The search for a new source of CP violation is one of the most important endeavors in particle physics. A particularly interesting way to perform this search is to probe the CP phase in the $h\\tau\\tau$ coupling, as the phase is currently completely unconstrained by all existing data. Recently, a novel variable $\\Theta$ was proposed for measuring the CP phase in the $h\\tau\\tau$ coupling through the $\\tau^\\pm \\to \\pi^\\pm \\pi^0 \

  12. Quality characteristics and plasmin activity of thermosonicated skim milk and cream.

    PubMed

    Vijayakumar, S; Grewell, D; Annandarajah, C; Benner, L; Clark, S

    2015-10-01

    The shelf life of pasteurized milk is limited by heat-stable proteases, which cause gelation and bitter taste upon extended storage of milk. Ultra-high temperature processing inactivates proteases but detrimentally affects milk's sensory quality. An adjunct to pasteurization is desired to extend milk's shelf life while maintaining quality characteristics. In this study, the effects of combined heat and ultrasound (thermosonication) on total plasmin activity and various quality characteristics of skim milk and cream were studied. Thermosonication, at an average power of 115 W (152 µmp-p, where p-p=peak-to-peak amplitude) for 3 min, decreased the total plasmin activity (i.e., plasmin- and plasminogen-derived activity) by nearly 94% in fresh skim milk and cream. Enzyme activity in thermosonicated skim milk samples measured at the end of 30 d was 5- to 10-fold higher than on d 0, but remained stable in thermosonicated cream. Descriptive analysis of odor attributes was conducted for up to 4 wk with 8 trained panelists. No significant differences were observed between the intensities of offensive "eggy" and "rubbery" odor attributes of thermosonicated skim milk and pasteurized commercial skim milk and cream. In addition, lightness (L*) values and viscosity were not adversely affected by thermosonication. Thermosonication decreased the fat globule size in skim milk and cream, and the homogenizing effect increased with treatment time. Thermosonication at average powers of 104 W (133 µmp-p) and 115 W (152 µmp-p) for 1 and 3 min destroyed coliforms and over 99% of the total aerobic bacteria. The total aerobic bacteria counts of thermosonicated skim milk and cream samples were less than 20,000 cfu/mL on d 30. Because thermosonication did not induce off-aromas or viscosity changes but did inactivate microorganisms and protease enzymes, thermosonication may be an appropriate adjunct to pasteurization to extend milk shelf life. Copyright © 2015 American Dairy Science

  13. Neurofibrillary tangle-like tau pathology induced by synthetic tau fibrils in primary neurons over-expressing mutant tau.

    PubMed

    Guo, Jing L; Lee, Virginia M Y

    2013-03-18

    Increasing evidence demonstrates the transmissibility of fibrillar species of tau protein, but this has never been directly tested in neurons, the cell type most affected by formation of tau inclusions in neurodegenerative tauopathies. Here we show that synthetic tau fibrils made from recombinant protein not only time-dependently recruit normal tau into neurofibrillary tangle-like insoluble aggregates in primary hippocampal neurons over-expressing human tau, but also induce neuritic tau pathology in non-transgenic neurons. This study provides highly compelling support for the protein-only hypothesis of pathological tau transmission in primary neurons and describes a useful neuronal model for studying the pathogenesis of tauopathies. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  14. Tau-66: evidence for a novel tau conformation in Alzheimer's disease.

    PubMed

    Ghoshal, N; García-Sierra, F; Fu, Y; Beckett, L A; Mufson, E J; Kuret, J; Berry, R W; Binder, L I

    2001-06-01

    We have characterized a novel monoclonal antibody, Tau-66, raised against recombinant human tau. Immunohistochemistry using Tau-66 reveals a somatic-neuronal stain in the superior temporal gyrus (STG) that is more intense in Alzheimer's disease (AD) brain than in normal brain. In hippocampus, Tau-66 yields a pattern similar to STG, except that neurofibrillary lesions are preferentially stained if present. In mild AD cases, Tau-66 stains plaques lacking obvious dystrophic neurites (termed herein 'diffuse reticulated plaques') in STG and the hippocampus. Enzyme-linked immunosorbent assay (ELISA) analysis reveals that Tau-66 is specific for tau, as there is no cross-reactivity with MAP2, tubulin, Abeta(1-40), or Abeta(1-42), although Tau-66 fails to react with tau or any other polypeptide on western blots. The epitope of Tau-66, as assessed by ELISA testing of tau deletion mutants, appears discontinuous, requiring residues 155-244 and 305-314. Tau-66 reactivity exhibits buffer and temperature sensitivity in an ELISA format and is readily abolished by SDS treatment. Taken together these lines of evidence indicate that the Tau-66 epitope is conformation-dependent, perhaps involving a close interaction of the proline-rich and the third microtubule-binding regions. This is the first indication that tau can undergo this novel folding event and that this conformation of tau is involved in AD pathology.

  15. Evidence for B+ --> tau+ nu_tau Decays using Hadronic B Tags

    SciTech Connect

    del Amo Sanchez, P.; Lees, J.P.; Poireau, V.; Prencipe, E.; Tisserand, V.; Garra Tico, J.; Grauges, E.; Martinelli, M.; Milanes, D.A.; Palano, A.; Pappagallo, M.; Eigen, G.; Stugu, B.; Sun, L.; Brown, D.N.; Kerth, L.T.; Kolomensky, Yu.G.; Lynch, G.; Osipenkov, I.L.; Koch, H.; Schroeder, T.; /Ruhr U., Bochum /British Columbia U. /Brunel U. /Novosibirsk, IYF /UC, Irvine /UC, Riverside /UC, Santa Barbara /UC, Santa Cruz /Caltech /Cincinnati U. /Colorado U. /Colorado State U. /Dortmund U. /Dresden, Tech. U. /Ecole Polytechnique /Edinburgh U. /INFN, Ferrara /Ferrara U. /INFN, Ferrara /INFN, Ferrara /Ferrara U. /INFN, Ferrara /Frascati /INFN, Genoa /Genoa U. /INFN, Genoa /INFN, Genoa /Genoa U. /INFN, Genoa /INFN, Genoa /Genoa U. /Indian Inst. Tech., Guwahati /Harvard U. /Heidelberg U. /Humboldt U., Berlin /Imperial Coll., London /Iowa State U. /Iowa State U. /Johns Hopkins U. /Orsay, LAL /LLNL, Livermore /Liverpool U. /Queen Mary, U. of London /Royal Holloway, U. of London /Louisville U. /Mainz U., Inst. Kernphys. /Manchester U. /Maryland U. /Massachusetts U., Amherst /MIT /McGill U. /INFN, Milan /Milan U. /INFN, Milan /INFN, Milan /Milan U. /Mississippi U. /Montreal U. /INFN, Naples /Naples U. /NIKHEF, Amsterdam /Notre Dame U. /Ohio State U. /Oregon U. /INFN, Padua /Padua U. /INFN, Padua /INFN, Padua /Padua U. /Paris U., VI-VII /INFN, Perugia /Perugia U. /INFN, Pisa /Pisa U. /INFN, Pisa /Pisa, Scuola Normale Superiore /INFN, Pisa /Pisa U. /INFN, Pisa /Princeton U. /INFN, Rome /INFN, Rome /Rome U. /INFN, Rome /INFN, Rome /Rome U. /INFN, Rome /INFN, Rome /Rome U. /INFN, Rome /INFN, Rome /Rome U. /Rostock U. /Rutherford /DAPNIA, Saclay /SLAC /South Carolina U. /Southern Methodist U. /Stanford U., Phys. Dept. /SUNY, Albany /Tel Aviv U. /Tennessee U. /Texas U. /Texas U., Dallas /INFN, Turin /Turin U. /INFN, Trieste /Trieste U. /Valencia U. /Victoria U. /Warwick U. /Wisconsin U., Madison

    2011-08-11

    We present a search for the decay B{sup +} --> {tau}{sup +} {nu}{sub {tau}} using 467.8 x 10{sup 6} B{anti B} pairs collected at the {Upsilon}(4S) resonance with the BABAR detector at the SLAC PEP-II B-Factory. We select a sample of events with on completely reconstructed B{sup -} in an hadronic decay mode (B{sup -} --> D{sup (*)0}X{sup -} and B{sup -} --> J/{psi} X{sup -}). We examine the rest of the event to search for a B{sup +} --> {tau}{sup +} {nu}{sub {tau}} decay. We identify the {tau}{sup +} lepton in the following modes: {tau}{sup +} --> e{sup +} {nu}{sub e}{anti {nu}}{sub {tau}}, {tau}{sup +} --> {mu}{sup +} {nu}{sub {mu}}{anti {nu}}{sub {tau}}, {tau}{sup +} --> {pi}{sup +}{anti {nu}}{sub {tau}} and {tau}{sup +} --> {rho}{anti {nu}}{sub {tau}}. We find an excess of events with respect to expected background, which excludes the null signal hypothesis at the level of 3.3 {sigma} and can be converted to a branching fraction central value of B(B{sup +} --> {tau}{sup +} {nu}{sub {tau}})= (1.80{sup + 0.57}{sub - 0.54}(stat.) {+-} 0.26 (syst.)) x 10{sup -4}.

  16. Membrane fractionation processes for removing 90% to 95% of the lactose and sodium from skim milk and for preparing lactose and sodium-reduced skim milk.

    PubMed

    Morr, C V; Brandon, S C

    2008-11-01

    Pilot-scale microfiltration (MF), microfiltration-diafiltration (MDF), ultrafiltration (UF), ultrafiltration-diafiltration (UDF), and nanofilration (NF) membrane fractionation processes were designed and evaluated for removing 90% to 95% of the lactose and sodium from skim milk. The study was designed to evaluate several membrane fractionation schemes as a function of: (1) membrane types with and without diafiltration; (2) fractionation process temperatures ranging from 17 to 45 degrees C; (3) sources of commercial drinking water used as diafiltrant; and (4) final mass concentration ratios (MCR) ranging from about 2 to 5. MF and MDF membranes provided highest flux values, but were unsatisfactory because they failed to retain all of the whey proteins. UDF fractionation processes removed more than 90% to 95% of the lactose and sodium from skim milk. NF permeate prepared from UDF cumulative permeate contained sodium and other mineral concentrations that would make them unsuitable for use as a diafiltrant for UDF applications. A method was devised for preparing simulated milk permeate (SMP) formulated with calcium, magnesium, and potassium hydroxides, and phosphoric and citric acids for use as UDF diafiltrant or for preparing lactose and sodium reduced skim milk (L-RSM). MF retentates with MCR values of 4.7 to 5.0 exhibited extremely poor frozen storage stabilities of less than 1 wk at -20 degrees C, whereas MCR 1.77 to 2.95 MDF and UDF retentates and skim milk control exhibited frozen storage stabilities of more than 16 wk. L-RSM exhibited a whiter appearance and a lower viscosity than skim milk, lacked natural milk flavor, and exhibited a metallic off-flavor.

  17. Metagenome Skimming of Insect Specimen Pools: Potential for Comparative Genomics

    PubMed Central

    Linard, Benjamin; Crampton-Platt, Alex; Gillett, Conrad P.D.T.; Timmermans, Martijn J.T.N.; Vogler, Alfried P.

    2015-01-01

    Metagenomic analyses are challenging in metazoans, but high-copy number and repeat regions can be assembled from low-coverage sequencing by “genome skimming,” which is applied here as a new way of characterizing metagenomes obtained in an ecological or taxonomic context. Illumina shotgun sequencing on two pools of Coleoptera (beetles) of approximately 200 species each were assembled into tens of thousands of scaffolds. Repeated low-coverage sequencing recovered similar scaffold sets consistently, although approximately 70% of scaffolds could not be identified against existing genome databases. Identifiable scaffolds included mitochondrial DNA, conserved sequences with hits to expressed sequence tag and protein databases, and known repeat elements of high and low complexity, including numerous copies of rRNA and histone genes. Assemblies of histones captured a diversity of gene order and primary sequence in Coleoptera. Scaffolds with similarity to multiple sites in available coleopteran genome sequences for Dendroctonus and Tribolium revealed high specificity of scaffolds to either of these genomes, in particular for high-copy number repeats. Numerous “clusters” of scaffolds mapped to the same genomic site revealed intra- and/or intergenomic variation within a metagenome pool. In addition to effect of taxonomic composition of the metagenomes, the number of mapped scaffolds also revealed structural differences between the two reference genomes, although the significance of this striking finding remains unclear. Finally, apparently exogenous sequences were recovered, including potential food plants, fungal pathogens, and bacterial symbionts. The “metagenome skimming” approach is useful for capturing the genomic diversity of poorly studied, species-rich lineages and opens new prospects in environmental genomics. PMID:25979752

  18. Genome skimming identifies polymorphism in tern populations and species

    PubMed Central

    2012-01-01

    Background Terns (Charadriiformes: Sterninae) are a lineage of cosmopolitan shorebirds with a disputed evolutionary history that comprises several species of conservation concern. As a non-model system in genetics, previous study has left most of the nuclear genome unexplored, and population-level studies are limited to only 15% of the world's species of terns and noddies. Screening of polymorphic nuclear sequence markers is needed to enhance genetic resolution because of supposed low mitochondrial mutation rate, documentation of nuclear insertion of hypervariable mitochondrial regions, and limited success of microsatellite enrichment in terns. Here, we investigated the phylogenetic and population genetic utility for terns and relatives of a variety of nuclear markers previously developed for other birds and spanning the nuclear genome. Markers displaying a variety of mutation rates from both the nuclear and mitochondrial genome were tested and prioritized according to optimal cross-species amplification and extent of genetic polymorphism between (1) the main tern clades and (2) individual Royal Terns (Thalasseus maxima) breeding on the US East Coast. Results Results from this genome skimming effort yielded four new nuclear sequence-based markers for tern phylogenetics and 11 intra-specific polymorphic markers. Further, comparison between the two genomes indicated a phylogenetic conflict at the base of terns, involving the inclusion (mitochondrial) or exclusion (nuclear) of the Angel Tern (Gygis alba). Although limited mitochondrial variation was confirmed, both nuclear markers and a short tandem repeat in the mitochondrial control region indicated the presence of considerable genetic variation in Royal Terns at a regional scale. Conclusions These data document the value of intronic markers to the study of terns and allies. We expect that these and additional markers attained through next-generation sequencing methods will accurately map the genetic origin and

  19. Increased misfolding and truncation of tau in APP/PS1/tau transgenic mice compared to mutant tau mice.

    PubMed

    Héraud, Céline; Goufak, Doris; Ando, Kunie; Leroy, Karelle; Suain, Valérie; Yilmaz, Zehra; De Decker, Robert; Authelet, Michèle; Laporte, Vincent; Octave, Jean-Noël; Brion, Jean-Pierre

    2014-02-01

    Neurofibrillary degeneration in transgenic models of tauopathies has been observed to be enhanced when these models are crossed with transgenic models developing an Aβ pathology. The mechanisms leading to this enhanced tau pathology are not well understood. We have performed a detailed analysis of tau misprocessing in a new transgenic mouse model combining APP, PS1 and tau mutations (5xFAD×Tg30 mice) by comparison with littermates expressing only a FTD mutant tau (Tg30 mice). These 5xFAD×Tg30 mice showed a more severe deficient motor phenotype than Tg30 mice and developed with age a dramatically accelerated NFT load in the brain compared to Tg30 mice. Insoluble tau in 5xFAD×Tg30 mice compared to insoluble tau in Tg30 mice showed increased phosphorylation, enhanced misfolding and truncation changes mimicking more closely the post-translational changes characteristic of PHF-tau in Alzheimer's disease. Endogenous wild-type mouse tau was recruited at much higher levels in insoluble tau in 5xFAD×Tg30 than in Tg30 mice. Extracellular amyloid load, Aβ40 and Aβ42, β-CTFs and β-CTF phosphorylation levels were lower in 5xFAD×Tg30 mice than in 5xFAD mice. Despite this reduction of Aβ, a significant hippocampal neuronal loss was observed in 5xFAD×Tg30 but not in 5xFAD mice indicating its closer association with increased tau pathology. This 5xFAD×Tg30 model thus mimics more faithfully tau pathology and neuronal loss observed in AD and suggests that additional post-translational changes in tau and self-recruitment of endogenous tau drive the enhanced tau pathology developing in the presence of Aβ pathology. © 2013.

  20. New results on the tau lepton

    SciTech Connect

    Gan, K.K.

    1987-11-01

    This is a review of new results on the tau lepton. The results include precise measurements of the lifetime, measurements of the decay tau/sup -/ ..-->.. ..pi../sup -/2..pi../sup 0/nu/sub tau/ with much improved precision, and limits on decay modes containing eta mesons, including the second-class-current decay tau/sup -/ ..-->.. ..pi../sup -/eta nu/sub tau/. The implications of these new results on the discrepancy in the one-charged-particle decay modes are discussed. 52 refs., 6 figs., 2 tabs.

  1. Leptin Levels Are Higher in Whole Compared to Skim Human Milk, Supporting a Cellular Contribution.

    PubMed

    Kugananthan, Sambavi; Lai, Ching Tat; Gridneva, Zoya; Mark, Peter J; Geddes, Donna T; Kakulas, Foteini

    2016-11-08

    Human milk (HM) contains a plethora of metabolic hormones, including leptin, which is thought to participate in the regulation of the appetite of the developing infant. Leptin in HM is derived from a combination of de novo mammary synthesis and transfer from the maternal serum. Moreover, leptin is partially lipophilic and is also present in HM cells. However, leptin has predominately been measured in skim HM, which contains neither fat nor cells. We optimised an enzyme-linked immunosorbent assay for leptin measurement in both whole and skim HM and compared leptin levels between both HM preparations collected from 61 lactating mothers. Whole HM leptin ranged from 0.2 to 1.47 ng/mL, whilst skim HM leptin ranged from 0.19 to 0.9 ng/mL. Whole HM contained, on average, 0.24 ± 0.01 ng/mL more leptin than skim HM (p < 0.0001, n = 287). No association was found between whole HM leptin and fat content (p = 0.17, n = 287), supporting a cellular contribution to HM leptin. No difference was found between pre- and post-feed samples (whole HM: p = 0.29, skim HM: p = 0.89). These findings highlight the importance of optimising HM leptin measurement and assaying it in whole HM to accurately examine the amount of leptin received by the infant during breastfeeding.

  2. Skimming behaviour and spreading potential of Stenus species and Dianous coerulescens (Coleoptera: Staphylinidae)

    NASA Astrophysics Data System (ADS)

    Lang, Carolin; Seifert, Karlheinz; Dettner, Konrad

    2012-11-01

    Rove beetles of the genus Stenus Latreille and the genus Dianous Leach possess pygidial glands containing a multifunctional secretion of piperidine and pyridine-derived alkaloids as well as several terpenes. One important character of this secretion is the spreading potential of its different compounds, stenusine, norstenusine, 3-(2-methyl-1-butenyl)pyridine, cicindeloine, α-pinene, 1,8-cineole and 6-methyl-5-heptene-2-one. The individual secretion composition enables the beetles to skim rapidly and far over the water surface, even when just a small amount of secretion is emitted. Ethological investigations of several Stenus species revealed that the skimming ability, skimming velocity and the skimming behaviour differ between the Stenus species. These differences can be linked to varied habitat claims and secretion saving mechanisms. By means of tensiometer measurements using the pendant drop method, the spreading pressure of all secretion constituents as well as some naturally identical beetle secretions on the water surface could be established. The compound 3-(2-methyl-1-butenyl)pyridine excelled stenusine believed to date to be mainly responsible for skimming relating to its surface activity. The naturally identical secretions are not subject to synergistic effects of the single compounds concerning the spreading potential. Furthermore, evolutionary aspects of the Steninae's pygidial gland secretion are discussed.

  3. Comparison of rat hepatic cholesterol biosynthesis during skim milk versus whey permeate ingestion.

    PubMed

    Keim, N L; Marlett, J A; Amundson, C H; Hagemann, L D

    1982-12-01

    Whey permeate is an ultrafiltrate of whey that is devoid of protein but contains lactose, salts, and other soluble low molecular weight compounds. These experiments compared cholesterol concentrations of blood plasma, hepatic lipids, and hepatic cholesterol biosynthesis of rats ingesting skim milk powder versus whey permeate powder. Groups of young male rats weighing 90 to 92 g were fed a casein-based diet into which skim milk powder or whey permeate powder was incorporated isocalorically. No effects of skim milk or whey permeate on plasma cholesterol concentrations were observed at any time during 5-wk of feeding. However, 3-hydroxy-3-methylglutaryl co-enzyme A reductase activity was increased by either skim milk or whey permeate feeding. Hepatic cholesterol, triglyceride, and phospholipid concentrations at wk 5 were unchanged. Plasma and hepatic cholesterol responses of rats to whey permeate ingestion are similar to those that occur with skim milk consumption, and plasma and hepatic cholesterol concentrations do not reflect necessarily an increase in hepatic cholesterol biosynthesis.

  4. Leptin Levels Are Higher in Whole Compared to Skim Human Milk, Supporting a Cellular Contribution

    PubMed Central

    Kugananthan, Sambavi; Lai, Ching Tat; Gridneva, Zoya; Mark, Peter J.; Geddes, Donna T.; Kakulas, Foteini

    2016-01-01

    Human milk (HM) contains a plethora of metabolic hormones, including leptin, which is thought to participate in the regulation of the appetite of the developing infant. Leptin in HM is derived from a combination of de novo mammary synthesis and transfer from the maternal serum. Moreover, leptin is partially lipophilic and is also present in HM cells. However, leptin has predominately been measured in skim HM, which contains neither fat nor cells. We optimised an enzyme-linked immunosorbent assay for leptin measurement in both whole and skim HM and compared leptin levels between both HM preparations collected from 61 lactating mothers. Whole HM leptin ranged from 0.2 to 1.47 ng/mL, whilst skim HM leptin ranged from 0.19 to 0.9 ng/mL. Whole HM contained, on average, 0.24 ± 0.01 ng/mL more leptin than skim HM (p < 0.0001, n = 287). No association was found between whole HM leptin and fat content (p = 0.17, n = 287), supporting a cellular contribution to HM leptin. No difference was found between pre- and post-feed samples (whole HM: p = 0.29, skim HM: p = 0.89). These findings highlight the importance of optimising HM leptin measurement and assaying it in whole HM to accurately examine the amount of leptin received by the infant during breastfeeding. PMID:27834797

  5. Extracellular monomeric tau protein is sufficient to initiate the spread of tau protein pathology.

    PubMed

    Michel, Claire H; Kumar, Satish; Pinotsi, Dorothea; Tunnacliffe, Alan; St George-Hyslop, Peter; Mandelkow, Eckhard; Mandelkow, Eva-Maria; Kaminski, Clemens F; Kaminski Schierle, Gabriele S

    2014-01-10

    Understanding the formation and propagation of aggregates of the Alzheimer disease-associated Tau protein in vivo is vital for the development of therapeutics for this devastating disorder. Using our recently developed live-cell aggregation sensor in neuron-like cells, we demonstrate that different variants of exogenous monomeric Tau, namely full-length Tau (hTau40) and the Tau-derived construct K18 comprising the repeat domain, initially accumulate in endosomal compartments, where they form fibrillar seeds that subsequently induce the aggregation of endogenous Tau. Using superresolution imaging, we confirm that fibrils consisting of endogenous and exogenous Tau are released from cells and demonstrate their potential to spread Tau pathology. Our data indicate a greater pathological risk and potential toxicity than hitherto suspected for extracellular soluble Tau.

  6. Extracellular Monomeric Tau Protein Is Sufficient to Initiate the Spread of Tau Protein Pathology*

    PubMed Central

    Michel, Claire H.; Kumar, Satish; Pinotsi, Dorothea; Tunnacliffe, Alan; St. George-Hyslop, Peter; Mandelkow, Eckhard; Mandelkow, Eva-Maria; Kaminski, Clemens F.; Kaminski Schierle, Gabriele S.

    2014-01-01

    Understanding the formation and propagation of aggregates of the Alzheimer disease-associated Tau protein in vivo is vital for the development of therapeutics for this devastating disorder. Using our recently developed live-cell aggregation sensor in neuron-like cells, we demonstrate that different variants of exogenous monomeric Tau, namely full-length Tau (hTau40) and the Tau-derived construct K18 comprising the repeat domain, initially accumulate in endosomal compartments, where they form fibrillar seeds that subsequently induce the aggregation of endogenous Tau. Using superresolution imaging, we confirm that fibrils consisting of endogenous and exogenous Tau are released from cells and demonstrate their potential to spread Tau pathology. Our data indicate a greater pathological risk and potential toxicity than hitherto suspected for extracellular soluble Tau. PMID:24235150

  7. Tau reduction prevents neuronal loss and reverses pathological tau deposition and seeding in mice with tauopathy.

    PubMed

    DeVos, Sarah L; Miller, Rebecca L; Schoch, Kathleen M; Holmes, Brandon B; Kebodeaux, Carey S; Wegener, Amy J; Chen, Guo; Shen, Tao; Tran, Hien; Nichols, Brandon; Zanardi, Tom A; Kordasiewicz, Holly B; Swayze, Eric E; Bennett, C Frank; Diamond, Marc I; Miller, Timothy M

    2017-01-25

    Accumulation of hyperphosphorylated tau directly correlates with cognitive decline in Alzheimer's disease and other primary tauopathies. One therapeutic strategy may be to reduce total tau expression. We identified antisense oligonucleotides (ASOs) that selectively decreased human tau mRNA and protein in mice expressing mutant P301S human tau. After reduction of human tau in this mouse model of tauopathy, fewer tau inclusions developed, and preexisting phosphorylated tau and Thioflavin S pathology were reversed. The resolution of tau pathology was accompanied by the prevention of hippocampal volume loss, neuronal death, and nesting deficits. In addition, mouse survival was extended, and pathological tau seeding was reversed. In nonhuman primates, tau ASOs distributed throughout the brain and spinal cord and reduced tau mRNA and protein in the brain, spinal cord, and cerebrospinal fluid. These data support investigation of a tau-lowering therapy in human patients who have tau-positive inclusions even after pathological tau deposition has begun. Copyright © 2017, American Association for the Advancement of Science.

  8. Seeding of Normal Tau by Pathological Tau Conformers Drives Pathogenesis of Alzheimer-like Tangles*

    PubMed Central

    Guo, Jing L.; Lee, Virginia M.-Y.

    2011-01-01

    Neurofibrillary tangles (NFTs) in Alzheimer disease and related tauopathies are composed of insoluble hyperphosphorylated Tau protein, but the mechanisms underlying the conversion of highly soluble Tau into insoluble NFTs remain elusive. Here, we demonstrate that introduction of minute quantities of misfolded preformed Tau fibrils (Tau pffs) into Tau-expressing cells rapidly recruit large amounts of soluble Tau into filamentous inclusions resembling NFTs with unprecedented efficiency, suggesting a “seeding”-recruitment process as a highly plausible mechanism underlying NFT formation in vivo. Consistent with the emerging concept of prion-like transmissibility of disease-causing amyloidogenic proteins, we found that spontaneous uptake of Tau pffs into cells is likely mediated by endocytosis, suggesting a potential mechanism for the propagation of Tau lesions in tauopathy brains. Furthermore, sequestration of soluble Tau by pff-induced Tau aggregates attenuates microtubule overstabilization in Tau-expressing cells, supporting the hypothesis of a Tau loss-of-function toxicity in cells harboring NFTs. In summary, our study establishes a cellular system that robustly develops authentic NFT-like Tau aggregates, which provides mechanistic insights into NFT pathogenesis and a potential tool for identifying Tau-based therapeutics. PMID:21372138

  9. Prefibrillar Tau oligomers alter the nucleic acid protective function of Tau in hippocampal neurons in vivo.

    PubMed

    Violet, Marie; Chauderlier, Alban; Delattre, Lucie; Tardivel, Meryem; Chouala, Meliza Sendid; Sultan, Audrey; Marciniak, Elodie; Humez, Sandrine; Binder, Lester; Kayed, Rakez; Lefebvre, Bruno; Bonnefoy, Eliette; Buée, Luc; Galas, Marie-Christine

    2015-10-01

    The accumulation of DNA and RNA oxidative damage is observed in cortical and hippocampal neurons from Alzheimer's disease (AD) brains at early stages of pathology. We recently reported that Tau is a key nuclear player in the protection of neuronal nucleic acid integrity in vivo under physiological conditions and hyperthermia, a strong inducer of oxidative stress. In a mouse model of tauopathy (THY-Tau22), we demonstrate that hyperthermia selectively induces nucleic acid oxidative damage and nucleic acid strand breaks in the nucleus and cytoplasm of hippocampal neurons that display early Tau phosphorylation but no Tau fibrils. Nucleic acid-damaged neurons were exclusively immunoreactive for prefibrillar Tau oligomers. A similar association between prefibrillar Tau oligomers and nucleic acid oxidative damage was observed in AD brains. Pretreatment with Methylene Blue (MB), a Tau aggregation inhibitor and a redox cycler, reduced hyperthermia-induced Tau oligomerization as well as nucleic acid damage. This study clearly highlights the existence of an early and critical time frame for hyperthermia-induced Tau oligomerization, which most likely occurs through increased oxidative stress, and nucleic acid vulnerability during the progression of Tau pathology. These results suggest that at early stages of AD, Tau oligomerization triggers the loss of the nucleic acid protective function of monomeric Tau. This study highlights the existence of a short therapeutic window in which to prevent the formation of pathological forms of Tau and their harmful consequences on nucleic acid integrity during the progression of Tau pathology. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Constraints on the {tau} neutrino mass and mixing from precise measurements of {tau} decay rates

    SciTech Connect

    Swain, J.; Taylor, L.

    1997-01-01

    We have derived constraints on the {tau} neutrino mass and fourth generation mixing from an analysis of the partial widths of {tau} lepton decays, in particular, {tau}{sup {minus}}{r_arrow}e{sup {minus}}{bar {nu}}{sub e}{nu}{sub {tau}}, {tau}{sup {minus}}{r_arrow}{mu}{sup {minus}}{bar {nu}}{sub {mu}}{nu}{sub {tau}}, {tau}{r_arrow}{pi}{sup {minus}}{nu}{sub {tau}}, and {tau}{r_arrow}K{sup {minus}}{nu}{sub {tau}}. We present predictions for the {tau} decay widths, allowing for a nonzero {tau} neutrino mass m{sub {nu}{sub {tau}}} and for mixing with a neutrino of mass m{sub {nu}{sub L}}{gt}M{sub Z}/2, which is parametrized using a Cabibbo-like mixing angle {theta}{sub L}. By comparison of these theoretical predictions with the experimental measurements, we obtain the following bounds at the 90{percent} confidence level: m{sub {nu}{sub {tau}}}{lt}42 MeV and sin{sup 2}{theta}{sub L}{lt}0.014. {copyright} {ital 1997} {ital The American Physical Society}

  11. Secretion of full-length tau or tau fragments in a cell culture model.

    PubMed

    Pérez, Mar; Cuadros, Raquel; Hernández, Félix; Avila, Jesús

    2016-11-10

    Tau is a microtubule-associated protein that plays an important role in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease. Several studies have suggested that tau may be secreted to extracellular medium and may be responsible of spreading of neurodegeneration. The overexpression of tau in cultured non-neuronal cells leads to the secretion of this protein. The proline-rich region of tau may serve as a membrane-binding site during the secretion of the full-length tau molecule. Tau fragments lacking this proline-region are either not secreted or are secreted in a distinct manner to the full-length molecule.

  12. Video Skimming and Characterization through the Combination of Image and Language Understanding Techniques

    NASA Technical Reports Server (NTRS)

    Smith, Michael A.; Kanade, Takeo

    1997-01-01

    Digital video is rapidly becoming important for education, entertainment, and a host of multimedia applications. With the size of the video collections growing to thousands of hours, technology is needed to effectively browse segments in a short time without losing the content of the video. We propose a method to extract the significant audio and video information and create a "skim" video which represents a very short synopsis of the original. The goal of this work is to show the utility of integrating language and image understanding techniques for video skimming by extraction of significant information, such as specific objects, audio keywords and relevant video structure. The resulting skim video is much shorter, where compaction is as high as 20:1, and yet retains the essential content of the original segment.

  13. Use of fluorometry for determination of skim milk powder adulteration in fresh milk*

    PubMed Central

    Guan, Rong-fa; Liu, Dong-hong; Ye, Xing-qian; Yang, Kai

    2005-01-01

    A FAST (fluorescence of advanced Maillard products and Soluble Tryptophan) method for identification of reconstituted milk made from skim milk powder in the fresh milk was developed. Considering milk and skim milk powders variations from different seasons and countries, milk was collected from different dairy farms in different seasons and skim milk powders were collected from different countries to measure the Tryptophan (Trp), advanced Maillard products (AMP) fluorescence values. The results showed that there were differences (P<0.01) between raw and reconstituted milk. The plot of values in each mixed level of raw and reconstituted milk had a correlation coefficient >0.97. The FAST method is a simple, rapid, low-cost and sensitive method enabling the detection of 5% reconstituted milk in fresh milk. The measurement of the Trp, AMP fluorescence values and calculation of the FAST index is a suitable method for large-scale monitoring of fresh milk samples. PMID:16252345

  14. Use of fluorometry for determination of skim milk powder adulteration in fresh milk.

    PubMed

    Guan, Rong-fa; Liu, Dong-hong; Ye, Xing-qian; Yang, Kai

    2005-11-01

    A FAST (fluorescence of advanced Maillard products and Soluble Tryptophan) method for identification of reconstituted milk made from skim milk powder in the fresh milk was developed. Considering milk and skim milk powders variations from different seasons and countries, milk was collected from different dairy farms in different seasons and skim milk powders were collected from different countries to measure the Tryptophan (Trp), advanced Maillard products (AMP) fluorescence values. The results showed that there were differences (P<0.01) between raw and reconstituted milk. The plot of values in each mixed level of raw and reconstituted milk had a correlation coefficient >0.97. The FAST method is a simple, rapid, low-cost and sensitive method enabling the detection of 5% reconstituted milk in fresh milk. The measurement of the Trp, AMP fluorescence values and calculation of the FAST index is a suitable method for large-scale monitoring of fresh milk samples.

  15. Changes in tau phosphorylation in hibernating rodents.

    PubMed

    León-Espinosa, Gonzalo; García, Esther; García-Escudero, Vega; Hernández, Félix; Defelipe, Javier; Avila, Jesús

    2013-07-01

    Tau is a cytoskeletal protein present mainly in the neurons of vertebrates. By comparing the sequence of tau molecule among different vertebrates, it was found that the variability of the N-terminal sequence in tau protein is higher than that of the C-terminal region. The N-terminal region is involved mainly in the binding of tau to cellular membranes, whereas the C-terminal region of the tau molecule contains the microtubule-binding sites. We have compared the sequence of Syrian hamster tau with the sequences of other hibernating and nonhibernating rodents and investigated how differences in the N-terminal region of tau could affect the phosphorylation level and tau binding to cell membranes. We also describe a change, in tau phosphorylation, on a casein kinase 1 (ck1)-dependent site that is found only in hibernating rodents. This ck1 site seems to play an important role in the regulation of tau binding to membranes. Copyright © 2013 Wiley Periodicals, Inc.

  16. Binding of vitamin A by casein micelles in commercial skim milk.

    PubMed

    Mohan, M S; Jurat-Fuentes, J L; Harte, F

    2013-02-01

    Recent studies have shown that reassembled micelles formed by caseinates and purified casein fractions (α(s)- and β-casein) bind to hydrophobic compounds, including curcumin, docosahexaenoic acid, and vitamin D. However, limited research has been done on the binding of hydrophobic compounds by unmodified casein micelles in skim milk. In the present study, we investigated the ability of casein micelles in commercial skim milk to associate with vitamin A (retinyl palmitate), a fat-soluble vitamin commonly used to fortify milk. Milk protein fractions from different commercially available skim milk samples subjected to different processing treatments, including pasteurized, ultrapasteurized, organic pasteurized, and organic ultrapasteurized milks, were separated by fast protein liquid chromatography. The fractions within each peak were combined and freeze-dried. Sodium dodecyl sulfate-PAGE with silver staining was used to identify the proteins present in each of the fractions. The skim milk samples and fractions were extracted for retinyl palmitate and quantified against a standard using normal phase-HPLC. Retinyl palmitate was found to associate with the fraction of skim milk containing caseins, whereas the other proteins (BSA, β-lactoglobulin, α-lactalbumin) did not show any binding. The retinyl palmitate content in the various samples ranged from 1.59 to 2.48 µg of retinyl palmitate per mL of milk. The casein fractions contained between 14 and 40% of total retinyl palmitate in the various milks tested. The variation in the retention of vitamin A by caseins was probably explained by differences in the processing of different milk samples, including thermal treatment, the form of vitamin A emulsion used for fortification, and the point of fortification during processing. Unmodified casein micelles have a strong intrinsic affinity toward the binding of vitamin A used to fortify commercially available skim milks.

  17. Plasma Skimming in a Spiral Groove Bearing of a Centrifugal Blood Pump.

    PubMed

    Murashige, Tomotaka; Sakota, Daisuke; Kosaka, Ryo; Nishida, Masahiro; Kawaguchi, Yasuo; Yamane, Takashi; Maruyama, Osamu

    2016-09-01

    Plasma skimming is a phenomenon in which discharge hematocrit is lower than feed hematocrit in microvessels. Plasma skimming has been investigated at a bearing gap in a spiral groove bearing (SGB), as this has the potential to prevent hemolysis in the SGB of a blood pump. However, it is not clear whether plasma skimming occurs in a blood pump with the SGB, because the hematocrit has not been obtained. The purpose of this study is to verify plasma skimming in an SGB of a centrifugal blood pump by developing a hematocrit measurement method in an SGB. Erythrocyte observation using a high-speed microscope and a bearing gap measurement using a laser confocal displacement meter was performed five times. In these tests, bovine blood as a working fluid was diluted with autologous plasma to adjust the hematocrit to 1.0%. A resistor was adjusted to achieve a pressure head of 100 mm Hg and a flow rate of 5.0 L/min at a rotational speed of 2800 rpm. Hematocrit on the ridge region in the SGB was measured using an image analysis based on motion image of erythrocytes, mean corpuscular volume, the measured bearing gap, and a cross-sectional area of erythrocyte. Mean hematocrit on the ridge region in the SGB was linearly reduced from 0.97 to 0.07% with the decreasing mean bearing gap from 38 to 21 μm when the rotational speed was changed from 2250 to 3000 rpm. A maximum plasma skimming efficiency of 93% was obtained with a gap of 21 μm. In conclusion, we succeeded in measuring the hematocrit on the ridge region in the SGB of the blood pump. Hematocrit decreased on the ridge region in the SGB and plasma skimming occurred with a bearing gap of less than 30 μm in the hydrodynamically levitated centrifugal blood pump.

  18. Binding of vitamin A by casein micelles in commercial skim milk

    PubMed Central

    Mohan, M. S.; Jurat-Fuentes, J. L.; Harte, F.

    2015-01-01

    Recent studies have shown that reassembled micelles formed by caseinates and purified casein fractions (αs- and β-casein) bind to hydrophobic compounds, including curcumin, docosahexaenoic acid, and vitamin D. However, limited research has been done on the binding of hydrophobic compounds by unmodified casein micelles in skim milk. In the present study, we investigated the ability of casein micelles in commercial skim milk to associate with vitamin A (retinyl palmitate), a fat-soluble vitamin commonly used to fortify milk. Milk protein fractions from different commercially available skim milk samples subjected to different processing treatments, including pasteurized, ultrapasteurized, organic pasteurized, and organic ultrapasteurized milks, were separated by fast protein liquid chromatography. The fractions within each peak were combined and freeze-dried. Sodium dodecyl sulfate-PAGE with silver staining was used to identify the proteins present in each of the fractions. The skim milk samples and fractions were extracted for retinyl palmitate and quantified against a standard using normal phase-HPLC. Retinyl palmitate was found to associate with the fraction of skim milk containing caseins, whereas the other proteins (BSA, β-lactoglobulin, α-lactalbumin) did not show any binding. The retinyl palmitate content in the various samples ranged from 1.59 to 2.48 μg of retinyl palmitate per mL of milk. The casein fractions contained between 14 and 40% of total retinyl palmitate in the various milks tested. The variation in the retention of vitamin A by caseins was probably explained by differences in the processing of different milk samples, including thermal treatment, the form of vitamin A emulsion used for fortification, and the point of fortification during processing. Unmodified casein micelles have a strong intrinsic affinity toward the binding of vitamin A used to fortify commercially available skim milks. PMID:23261375

  19. Manufacture of acid gels from skim milk using high-pressure homogenization.

    PubMed

    Hernández, A; Harte, F M

    2008-10-01

    The effect of high-pressure homogenization (HPH) alone or in combination with a thermal treatment (TT) was investigated for the manufacture of acid gels from skim milk. Raw skim milk was subjected to HPH (0 to 350 MPa) or a TT (90 degrees C, 5 min), or both, in the following processing combinations: 1) HPH, 2) HPH followed by TT, 3) TT followed by HPH, 4) TT, and 5) raw milk (control). After treatments, L* (lightness) values were measured, and then skim milk was acidified with 3% glucono-delta-lactone and rheological properties (G' and gelation time), and whey holding capacity was evaluated. Treatments in which HPH and TT were combined showed greater L* values than those in which just HPH was applied. In all treatments, the L* values decreased as the pressure was increased up to 300 MPa with little change afterward. Gelation times were lower when HPH was combined with TT compared with the acid skim milk gels that were just pressure treated. The final G' in gels obtained from skim milk subjected to the combined process (HPH and TT) was greater and pressure-dependent compared with all other gels. A maximum G' (~320 Pa) was observed with skim milk subjected to a combination of thermal processing before or after HPH at 350 MPa. Acid gels obtained from HPH milk at 350 MPa showed a linear decrease in whey holding capacity over time, retaining 20% more whey after centrifugation for 25 min compared with samples treated at lower pressures and all other treatments. Our results suggest that HPH in combination with TT can be used to improve the rheological properties and stability of yogurt, thus decreasing the need for additives.

  20. Extracellular association of APP and tau fibrils induces intracellular aggregate formation of tau.

    PubMed

    Takahashi, Muneaki; Miyata, Haruka; Kametani, Fuyuki; Nonaka, Takashi; Akiyama, Haruhiko; Hisanaga, Shin-ichi; Hasegawa, Masato

    2015-06-01

    Alzheimer's disease (AD) is characterized by extracellular amyloid β (Aβ) deposition and intracellular tau aggregation. Many studies have indicated some association between these processes, but it remains unknown how the two pathologies are linked. In this study, we investigated whether expression of amyloid precursor protein (APP) influences extracellular seed-dependent intracellular tau accumulation in cultured cells. Treatment of tau-expressing SH-SY5Y cells with Aβ fibrils did not induce intracellular tau aggregation. On the other hand, in cells expressing both tau and APP, treatment with tau fibrils or Sarkosyl-insoluble tau from AD brains induced intracellular tau aggregation. The seed-dependent intracellular tau aggregation was not induced by expression of APP lacking the extracellular domain. The amount of phosphorylated tau aggregates in cultured cells was dose dependently elevated in response to increased levels of APP on the cell membrane. Our results indicate that the extracellular region of APP is involved in uptake of tau fibrils into cells, raising the possibility that APP, but not Aβ, influences cell-to-cell spreading of tau pathologies in AD by serving as a receptor of abnormal tau aggregates.

  1. Exploring authentic skim milk powder variance for the development of nontargeted adulterant detection methods using NIR spectroscopy and chemometrics

    USDA-ARS?s Scientific Manuscript database

    A multinational collaborative team led by the US Pharmacopeial Convention is currently investigating the potential of NIR spectroscopy for nontargeted detection of adulterants in skim milk powder. The development of a compendial method is challenged by the range of authentic or nonadulterated skim m...

  2. Tau as a biomarker of neurodegenerative diseases

    PubMed Central

    Schraen-Maschke, Susanna; Sergeant, Nicolas; Dhaenens, Claire-Marie; Bombois, Stephanie; Deramecourt, Vincent; Caillet-Boudin, Marie-Laure; Pasquier, Florence; Maurage, Claude-Alain; Sablonniere, Bernard; Vanmechelen, Eugeen; Buee, Luc

    2008-01-01

    Summary The microtubule associated protein Tau is mainly expressed in neurons of the central nervous system and is crucial in axonal maintenance and axonal transport. The rationale for Tau as a biomarker of neurodegenerative diseases is that it is a major component of abnormal intraneuronal aggregates observed in numerous of these diseases named Tauopathies, including Alzheimer’s disease. The molecular diversity of Tau is very useful when analysing it in the brain or in the peripheral fluids. Immunohistochemical and biochemical characterisation of Tau aggregates in the brain allows the post-mortem classification and differential diagnosis of Tauopathies. As peripheral biomarker of Alzheimer’s disease in the cerebrospinal fluid, Tau proteins are now validated for diagnosis and predictive purposes. For the future, the detailed characterization of Tau in brain and in peripheral fluids will lead to novel promising biomarkers for differential diagnosis of dementia and monitoring of therapeutics. PMID:20477391

  3. Tau appearance in atmospheric neutrino interactions

    SciTech Connect

    Hall, Lawrence J.; Murayama, Hitoshi

    1998-10-24

    If the correct interpretation of the Super-Kamiokande atmospheric neutrino data is {nu}{sub {mu}} {yields} {nu}{sub {tau}} oscillation, the contained data sample should already have more than 10 {tau} appearance events. We study the challenging task of detecting the {tau}, focusing on the decay chain {tau}{sup {+-}} {yields} {rho}{sup {+-}} {yields} {pi}{sup {+-}}{pi}{sup 0} in events with quasi-elastic {tau} production. The background level, which is currently quite uncertain because of a lack of relevant neutral current data, can be measured by the near detector in the K2K experiment. Our estimates of the background suggest that it may be possible to detect {tau} appearance in Super-Kamiokande with 5-10 years of running.

  4. Tau Protein and Adult Hippocampal Neurogenesis

    PubMed Central

    Fuster-Matanzo, Almudena; Llorens-Martín, María; Jurado-Arjona, Jerónimo; Avila, Jesús; Hernández, Félix

    2012-01-01

    Tau protein is a microtubule-associated protein found in the axonal compartment that stabilizes neuronal microtubules under normal physiological conditions. Tau metabolism has attracted much attention because of its role in neurodegenerative disorders called tauopathies, mainly Alzheimer disease. Here, we review recent findings suggesting that axonal outgrowth in subgranular zone during adult hippocampal neurogenesis requires a dynamic microtubule network and tau protein facilitates to maintain that dynamic cytoskeleton. Those functions are carried out in part by tau isoform with only three microtubule-binding domains (without exon 10) and by presence of hyperphosphorylated tau forms. Thus, tau is a good marker and a valuable tool to study new axons in adult neurogenesis. PMID:22787440

  5. Increased 4R-Tau Induces Pathological Changes in a Human-Tau Mouse Model.

    PubMed

    Schoch, Kathleen M; DeVos, Sarah L; Miller, Rebecca L; Chun, Seung J; Norrbom, Michaela; Wozniak, David F; Dawson, Hana N; Bennett, C Frank; Rigo, Frank; Miller, Timothy M

    2016-06-01

    Pathological evidence for selective four-repeat (4R) tau deposition in certain dementias and exon 10-positioned MAPT mutations together suggest a 4R-specific role in causing disease. However, direct assessments of 4R toxicity have not yet been accomplished in vivo. Increasing 4R-tau expression without change to total tau in human tau-expressing mice induced more severe seizures and nesting behavior abnormality, increased tau phosphorylation, and produced a shift toward oligomeric tau. Exon 10 skipping could also be accomplished in vivo, providing support for a 4R-tau targeted approach to target 4R-tau toxicity and, in cases of primary MAPT mutation, eliminate the disease-causing mutation. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Distinct Therapeutic Mechanisms of Tau Antibodies

    PubMed Central

    Funk, Kristen E.; Mirbaha, Hilda; Jiang, Hong; Holtzman, David M.; Diamond, Marc I.

    2015-01-01

    Tauopathies are neurodegenerative diseases characterized by accumulation of Tau amyloids, and include Alzheimer disease and certain frontotemporal dementias. Trans-neuronal propagation of amyloid mediated by extracellular Tau may underlie disease progression. Consistent with this, active and passive vaccination studies in mouse models reduce pathology, although by unknown mechanisms. We previously reported that intracerebroventricular administration of three anti-Tau monoclonal antibodies (HJ8.5, HJ9.3, and HJ9.4) reduces pathology in a model overexpressing full-length mutant (P301S) human Tau. We now study effects of these three antibodies and a negative control antibody (HJ3.4) on Tau aggregate uptake into BV2 microglial-like cells and primary neurons. Antibody-independent Tau uptake into BV2 cells was blocked by heparin, consistent with a previously described role for heparan sulfate proteoglycans. Two therapeutic antibodies (HJ8.5 and HJ9.4) promoted uptake of full-length Tau fibrils into microglia via Fc receptors. Surprisingly, HJ9.3 promoted uptake of fibrils composed of the Tau repeat domain or Alzheimer disease-derived Tau aggregates, but failed to influence full-length recombinant Tau fibrils. Size fractionation of aggregates showed that antibodies preferentially promote uptake of larger oligomers (n ≥∼20-mer) versus smaller oligomers (n ∼10-mer) or monomer. No antibody inhibited uptake of full-length recombinant fibrils into primary neurons, but HJ9.3 blocked neuronal uptake of Tau repeat domain fibrils and Alzheimer disease-derived Tau. Antibodies thus have multiple potential mechanisms, including clearance via microglia and blockade of neuronal uptake. However these effects are epitope- and aggregate size-dependent. Establishing specific mechanisms of antibody activity in vitro may help in design and optimization of agents that are more effective in vivo. PMID:26126828

  7. Interaction of tau protein with model lipid membranes induces tau structural compaction and membrane disruption

    PubMed Central

    Jones, Emmalee M.; Dubey, Manish; Camp, Phillip J.; Vernon, Briana C.; Biernat, Jacek; Mandelkow, Eckhard; Majewski, Jaroslaw; Chi, Eva Y.

    2012-01-01

    The misfolding and aggregation of the intrinsically disordered, microtubule-associated tau protein into neurofibrillary tangles is implicated in the pathogenesis of Alzheimer's disease. However, the mechanisms of tau aggregation and toxicity remain unknown. Recent work has shown that lipid membrane can induce tau aggregation and that membrane permeabilization may serve as a pathway by which protein aggregates exert toxicity, suggesting that the plasma membrane may play dual roles in tau pathology. This prompted our investigation to assess tau's propensity to interact with membranes and to elucidate the mutually disruptive structural perturbations the interactions induce in both tau and the membrane. We show that although highly charged and soluble, the full-length tau (hTau40) is also highly surface active, selectively inserts into anionic DMPG lipid monolayers and induces membrane morphological changes. To resolve molecular-scale structural details of hTau40 associated with lipid membranes, X-ray and neutron scattering techniques are utilized. X-ray reflectivity indicates hTau40's presence underneath a DMPG monolayer and penetration into the lipid headgroups and tailgroups, whereas grazing incidence X-ray diffraction shows that hTau40 insertion disrupts lipid packing. Moreover, both air/water and DMPG lipid membrane interfaces induce the disordered hTau40 to partially adopt a more compact conformation with density similar to that of a folded protein. Neutron reflectivity shows that tau completely disrupts supported DMPG bilayers while leaving the neutral DPPC bilayer intact. Our results show that hTau40's strong interaction with anionic lipids induces tau structural compaction and membrane disruption, suggesting possible membrane-based mechanisms of tau aggregation and toxicity in neurodegenerative diseases. PMID:22401494

  8. The Polyphenol Altenusin Inhibits in Vitro Fibrillization of Tau and Reduces Induced Tau Pathology in Primary Neurons.

    PubMed

    Chua, Sook Wern; Cornejo, Alberto; van Eersel, Janet; Stevens, Claire H; Vaca, Inmaculada; Cueto, Mercedes; Kassiou, Michael; Gladbach, Amadeus; Macmillan, Alex; Lewis, Lev; Whan, Renee; Ittner, Lars M

    2017-04-19

    In Alzheimer's disease, the microtubule-associated protein tau forms intracellular neurofibrillary tangles (NFTs). A critical step in the formation of NFTs is the conversion of soluble tau into insoluble filaments. Accordingly, a current therapeutic strategy in clinical trials is aimed at preventing tau aggregation. Here, we assessed altenusin, a bioactive polyphenolic compound, for its potential to inhibit tau aggregation. Altenusin inhibits aggregation of tau protein into paired helical filaments in vitro. This was associated with stabilization of tau dimers and other oligomers into globular structures as revealed by atomic force microscopy. Moreover, altenusin reduced tau phosphorylation in cells expressing pathogenic tau, and prevented neuritic tau pathology induced by incubation of primary neurons with tau fibrils. However, treatment of tau transgenic mice did not improve neuropathology and functional deficits. Taken together, altenusin prevents tau fibrillization in vitro and induced tau pathology in neurons.

  9. Folding of the Tau Protein on Microtubules.

    PubMed

    Kadavath, Harindranath; Jaremko, Mariusz; Jaremko, Łukasz; Biernat, Jacek; Mandelkow, Eckhard; Zweckstetter, Markus

    2015-08-24

    Microtubules are regulated by microtubule-associated proteins. However, little is known about the structure of microtubule-associated proteins in complex with microtubules. Herein we show that the microtubule-associated protein Tau, which is intrinsically disordered in solution, locally folds into a stable structure upon binding to microtubules. While Tau is highly flexible in solution and adopts a β-sheet structure in amyloid fibrils, in complex with microtubules the conserved hexapeptides at the beginning of the Tau repeats two and three convert into a hairpin conformation. Thus, binding to microtubules stabilizes a unique conformation in Tau. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Tau regulates the subcellular localization of calmodulin

    SciTech Connect

    Barreda, Elena Gomez de

    2011-05-13

    Highlights: {yields} In this work we have tried to explain how a cytoplasmic protein could regulate a cell nuclear function. We have tested the role of a cytoplasmic protein (tau) in regulating the expression of calbindin gene. We found that calmodulin, a tau-binding protein with nuclear and cytoplasmic localization, increases its nuclear localization in the absence of tau. Since nuclear calmodulin regulates calbindin expression, a decrease in nuclear calmodulin, due to the presence of tau that retains it at the cytoplasm, results in a change in calbindin expression. -- Abstract: Lack of tau expression in neuronal cells results in a change in the expression of few genes. However, little is known about how tau regulates gene expression. Here we show that the presence of tau could alter the subcellular localization of calmodulin, a protein that could be located at the cytoplasm or in the nucleus. Nuclear calmodulin binds to co-transcription factors, regulating the expression of genes like calbindin. In this work, we have found that in neurons containing tau, a higher proportion of calmodulin is present in the cytoplasm compared with neurons lacking tau and that an increase in cytoplasmic calmodulin correlates with a higher expression of calbindin.

  11. In vivo tau imaging: obstacles and progress.

    PubMed

    Villemagne, Victor L; Okamura, Nobuyuki

    2014-06-01

    The military conflicts of the last decade have highlighted the growing problem of traumatic brain injury in combatants returning from the battlefield. The considerable evidence pointing at the accumulation of tau aggregates and its recognition as a risk factor in neurodegenerative conditions such as Alzheimer's disease have led to a major effort to develop selective tau ligands that would allow research into the physiopathologic underpinnings of traumatic brain injury and chronic traumatic encephalopathy in military personnel and the civilian population. These tracers will allow new insights into tau pathology in the human brain, facilitating research into causes, diagnosis, and treatment of traumatic encephalopathy and major neurodegenerative dementias, such as Alzheimer's disease and some variants of frontotemporal lobar degeneration, in which tau plays a role. The field of selective tau imaging has to overcome several obstacles, some of them associated with the idiosyncrasies of tau aggregation and others related to radiotracer design. A worldwide effort has focused on the development of imaging agents that will allow selective tau imaging in vivo. Recent progress in the development of these tracers is enabling the noninvasive assessment of the extent of tau pathology in the brain, eventually allowing the quantification of changes in tau pathology over time and its relation to cognitive performance, brain volumetrics, and other biomarkers, as well as assessment of efficacy and patient recruitment for antitau therapeutic trials. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  12. Formation and Propagation of Tau Oligomeric Seeds

    PubMed Central

    Gerson, Julia E.; Kayed, Rakez

    2013-01-01

    Tau misfolding and aggregation leads to the formation of neurofibrillary tangles (NFTs), which have long been considered one of the main pathological hallmarks for numerous neurodegenerative diseases known as tauopathies, including Alzheimer’s Disease (AD) and Parkinson’s Disease (PD). However, recent studies completed both in vitro and in vivo suggest that intermediate forms of tau, known as tau oligomers, between the monomeric form and NFTs are the true toxic species in disease and the best targets for anti-tau therapies. However, the exact mechanism by which the spread of pathology occurs is unknown. Evidence suggests that tau oligomers may act as templates for the misfolding of native tau, thereby seeding the spread of the toxic forms of the protein. Recently, researchers have reported the ability of tau oligomers to enter and exit cells, propagating from disease-affected regions to unaffected areas. While the mechanism by which the spreading of misfolded tau occurs has yet to be elucidated, there are a few different models which have been proposed, including cell membrane stress and pore-formation, endocytosis and exocytosis, and non-traditional secretion of protein not enclosed by a membrane. Coming to an understanding of how toxic tau species seed and spread through the brain will be crucial to finding effective treatments for neurodegenerative tauopathies. PMID:23882255

  13. Tau deletion promotes brain insulin resistance

    PubMed Central

    Marciniak, Elodie; Leboucher, Antoine; Caron, Emilie; Ahmed, Tariq; Tailleux, Anne; Dumont, Julie; Issad, Tarik; Gerhardt, Ellen; Pagesy, Patrick; Vileno, Margaux; Hamdane, Malika; Bantubungi, Kadiombo; Lancel, Steve; Demeyer, Dominique; Eddarkaoui, Sabiha; Vallez, Emmanuelle; Vieau, Didier; Humez, Sandrine; Faivre, Emilie; Grenier-Boley, Benjamin; Outeiro, Tiago F.; Amouyel, Philippe; Balschun, Detlef

    2017-01-01

    The molecular pathways underlying tau pathology–induced synaptic/cognitive deficits and neurodegeneration are poorly understood. One prevalent hypothesis is that hyperphosphorylation, misfolding, and fibrillization of tau impair synaptic plasticity and cause degeneration. However, tau pathology may also result in the loss of specific physiological tau functions, which are largely unknown but could contribute to neuronal dysfunction. In the present study, we uncovered a novel function of tau in its ability to regulate brain insulin signaling. We found that tau deletion leads to an impaired hippocampal response to insulin, caused by altered IRS-1 and PTEN (phosphatase and tensin homologue on chromosome 10) activities. Our data also demonstrate that tau knockout mice exhibit an impaired hypothalamic anorexigenic effect of insulin that is associated with energy metabolism alterations. Consistently, we found that tau haplotypes are associated with glycemic traits in humans. The present data have far-reaching clinical implications and raise the hypothesis that pathophysiological tau loss-of-function favors brain insulin resistance, which is instrumental for cognitive and metabolic impairments in Alzheimer’s disease patients. PMID:28652303

  14. Detecting tau in serum of transgenic animal models after tau immunotherapy treatment.

    PubMed

    d'Abramo, Cristina; Acker, Christopher M; Schachter, Joel B; Terracina, Giuseppe; Wang, Xiaohai; Forest, Stefanie K; Davies, Peter

    2016-01-01

    In the attempt to elucidate if the "peripheral sink hypothesis" could be a potential mechanism of action for tau removal in passive immunotherapy experiments, we have examined tau levels in serum of chronically injected JNPL3 and Tg4510 transgenic animals. Measurement of tau in serum of mice treated with tau antibodies is challenging because of the antibody interference in sandwich enzyme-linked immunosorbent assays. To address this issue, we have developed a heat-treatment protocol at acidic pH to remove interfering molecules from serum, with excellent recovery of tau. The present data show that pan-tau and conformational antibodies do increase tau in mouse sera. However, these concentrations in serum do not consistently correlate with reductions of tau pathology in brain, suggesting that large elevations of tau species measured in serum are not predictive of efficacy. Here, we describe a reliable method to detect tau in serum of transgenic animals that have undergone tau immunotherapy. Levels of tau in human serum are less than the sensitivity of current assays, although artifactual signals are common. The method may be useful in similarly treated humans, a situation in which false positive signals are likely. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Reactive microglia drive tau pathology and contribute to the spreading of pathological tau in the brain.

    PubMed

    Maphis, Nicole; Xu, Guixiang; Kokiko-Cochran, Olga N; Jiang, Shanya; Cardona, Astrid; Ransohoff, Richard M; Lamb, Bruce T; Bhaskar, Kiran

    2015-06-01

    Pathological aggregation of tau is a hallmark of Alzheimer's disease and related tauopathies. We have previously shown that the deficiency of the microglial fractalkine receptor (CX3CR1) led to the acceleration of tau pathology and memory impairment in an hTau mouse model of tauopathy. Here, we show that microglia drive tau pathology in a cell-autonomous manner. First, tau hyperphosphorylation and aggregation occur as early as 2 months of age in hTauCx3cr1(-/-) mice. Second, CD45(+) microglial activation correlates with the spatial memory deficit and spread of tau pathology in the anatomically connected regions of the hippocampus. Third, adoptive transfer of purified microglia derived from hTauCx3cr1(-/-) mice induces tau hyperphosphorylation within the brains of non-transgenic recipient mice. Finally, inclusion of interleukin 1 receptor antagonist (Kineret®) in the adoptive transfer inoculum significantly reduces microglia-induced tau pathology. Together, our results suggest that reactive microglia are sufficient to drive tau pathology and correlate with the spread of pathological tau in the brain.

  16. Apparent Behavioral Benefits of Tau Overexpression in P301L Tau Transgenic Mice

    PubMed Central

    Morgan, Dave; Munireddy, Sanjay; Alamed, Jennifer; DeLeon, Jason; Diamond, David M.; Bickford, Paula; Hutton, Michael; Lewis, Jada; McGowan, Eileen; Gordon, Marcia N.

    2010-01-01

    Transgenic mice expressing human tau containing the P301L tau mutation (JNPL3; tau mice) develop motor neuron loss, paralysis and death between 7 and 12 months. Surprisingly, at 5 and 7 months of age, tau transgenic mice were superior to other genotypes in the rotarod task, and had near perfect scores on the balance beam and coat hanger tests. One tau transgenic mouse was performing at a superior level in the rotarod one day prior to developing paralysis. Cognitive function was also normal in the tau mice evaluated in the radial arm water maze and the Y-maze tasks. We also crossed the tau transgenic mice with Tg2576 amyloid-β protein precursor (AβPP) transgenic mice. Although AβPP mice were deficient in the radial arm maze task, AβPP+tau mice were not impaired, implying a benefit of the tau transgene. Some mice were homozygous for the retinal degeneration mutation (rd/rd) and excluded from the genotype analysis. Only the water maze task discriminated the rd/rd mice from nontransgenic mice. In conclusion, it seems that the modest tau overexpression or the presence of mutant tau in the JNPL3 tau mice may provide some benefit with respect to motor and cognitive performance before the onset of paralysis. PMID:19096159

  17. Tau neutrinos underground: Signals of νμ-->ντ oscillations with extragalactic neutrinos

    NASA Astrophysics Data System (ADS)

    Dutta, Sharada Iyer; Reno, Mary Hall; Sarcevic, Ina

    2000-12-01

    The appearance of high energy tau neutrinos due to νμ-->ντ oscillations of extragalactic neutrinos can be observed by measuring the neutrino induced upward hadronic and electromagnetic showers and upward muons. We evaluate quantitatively the tau neutrino regeneration in the Earth for a variety of extragalactic neutrino fluxes. Charged-current interactions of the upward tau neutrinos below and in the detector, and the subsequent tau decay, create muons or hadronic and electromagnetic showers. The background for these events are muon neutrino and electron neutrino charged-current and neutral-current interactions, where in addition to extragalactic neutrinos, we consider atmospheric neutrinos. We find significant signal to background ratios for the hadronic combined with electromagnetic showers with energies above 10-100 TeV initiated by the extragalactic neutrinos. We show that the tau neutrinos from point sources also have the potential for discovery above a 1 TeV threshold. A kilometer-size neutrino telescope has a very good chance of detecting the appearance of tau neutrinos when both muon and hadronic combined with electromagnetic showers are detected.

  18. Hyb-Seq: combining target enrichment and genome skimming for plant phylogenomics

    Treesearch

    Kevin Weitemier; Shannon C.K. Straub; Richard C. Cronn; Mark Fishbein; Roswitha Schmickl; Angela McDonnell; Aaron. Liston

    2014-01-01

    • Premise of the study: Hyb-Seq, the combination of target enrichment and genome skimming, allows simultaneous data collection for low-copy nuclear genes and high-copy genomic targets for plant systematics and evolution studies. • Methods and Results: Genome and transcriptome assemblies for milkweed ( Asclepias syriaca ) were used to design enrichment probes for 3385...

  19. Development of a Raman chemical imaging detection method for authenticating skim milk powder

    USDA-ARS?s Scientific Manuscript database

    This research demonstrated that Raman chemical imaging coupled with a simple image classification algorithm can be used to detect multiple chemical adulterants in skim milk powder. Ammonium sulfate, dicyandiamide, melamine, and urea were mixed into the milk powder as chemical adulterants in the conc...

  20. Applying Metacognitive Strategies to Skimming Research Articles in an ESP Context

    ERIC Educational Resources Information Center

    Dhieb-Henia, Nebila

    2006-01-01

    The article focuses on explaining to post-secondary teachers how to teach their students to use metacognitive strategies to skim research articles in specialized fields. The author briefly explains metacognitive strategies in reading tasks and discusses the importance of strategy training and having a purpose in reading. The author then describes…

  1. Textural and sensory characteristics of whole and skimmed flavored set-type yogurt during long storage.

    PubMed

    Salvador, A; Fiszman, S M

    2004-12-01

    A study of refrigerated storage (10 degrees C for 91 d) of whole and skimmed flavored set-type yogurt was made. Comparison with storage at 20 degrees C for 21 d and 30 degrees C for 3 d (accelerated) was also carried out. Refrigerated storage yogurts were assessed by a trained panel and by a consumer panel. Trained-panel scores were correlated to instrumental data, and the acceptability data for long storage were studied using consumer criteria. In all cases, after-storage pH values barely changed over storage time, indicating that the yogurt samples did not develop much acidity under any of the storage conditions studied. The profile of the instrumental texture curves obtained corresponded to a firm gel, which broke after a plunger penetrated the sample, and the firmness values of the whole yogurt were lower than for the skimmed yogurt under all the storage conditions studied. From a microbiological point of view, the viability of the yogurts was adequate at the different storage times and temperatures studied, although those stored at 10 degrees C for long periods would not comply with some countries' minimum requirements. Logistic regression of the data from a 50-consumer sensory evaluation showed that the probability of the whole yogurt being accepted after 91 d storage at 10 degrees C was around 40%, whereas for the skimmed yogurt it was only 15%, largely because the skimmed yogurt developed certain negative attributes at an earlier stage of storage than the whole yogurt.

  2. Are Colombian Sickness Funds Cream Skimming Enrollees? An Analysis with Suggestions for Policy Improvement

    ERIC Educational Resources Information Center

    Trujillo, Antonio J.; McCalla, Dawn C.

    2004-01-01

    One of the primary objectives of Colombian social health insurance reform was to increase competition among for-profit insurers. Unfortunately, the flat capitated formula creates an opportunity for sickness funds to maximize reimbursement gains by "cream skimming"--selecting against unhealthy individuals. This paper explores sickness…

  3. Are Colombian Sickness Funds Cream Skimming Enrollees? An Analysis with Suggestions for Policy Improvement

    ERIC Educational Resources Information Center

    Trujillo, Antonio J.; McCalla, Dawn C.

    2004-01-01

    One of the primary objectives of Colombian social health insurance reform was to increase competition among for-profit insurers. Unfortunately, the flat capitated formula creates an opportunity for sickness funds to maximize reimbursement gains by "cream skimming"--selecting against unhealthy individuals. This paper explores sickness…

  4. On Mathematicians' Proof Skimming: A Reply to Inglis and Alcock

    ERIC Educational Resources Information Center

    Weber, Keith; Mejia-Ramos, Juan Pablo

    2013-01-01

    n a recent article, Inglis and Alcock (2012) contended that their data challenge the claim that when mathematicians validate proofs, they initially skim a proof to grasp its main idea before reading individual parts of the proof more carefully. This result is based on the fact that when mathematicians read proofs in their study, on average their…

  5. The effect of heat treatment and skimming on precipitate formation in caprine and bovine milks.

    PubMed

    Miloradovic, Zorana N; Kljajevic, Nemanja V; Jovanovic, Snezana T; Vucic, Tanja R; Macej, Ognjen D

    2015-02-01

    Caprine and bovine milks have a similar overall gross composition, but vary considerably in the ratios of their casein components. These differences in colloidal casein micelles could affect directly or indirectly the heat stability of caprine and bovine milks at their natural pH. In the present work, the differences in colloidal stability of caprine and bovine milk have been studied by analysing the effect of heat treatment and skimming on precipitation of proteins. Raw and heated milk samples (70 °C/5 min, 80°C/5 min and 90°C/5 min) were centrifuged at 600, 2000, and 4500  g . The amount of precipitate formed after skimming was measured and the protein composition of both precipitates and supernatants analysed using the SDS-PAGE (sodium dodecyl sulphate polyacrylamide gel electrophoresis) and densitometry. In caprine milk, the heat treatment prior to skimming had a statistically significant effect on protein precipitation. Centrifugal force had a statistically significant effect on amount of precipitate for both milks, but the amount was 2 to 4 times higher for caprine milk. When defatting the milk for electrophoresis, a centrifugal force of 600  g appeared to be the most appropriate, in order to avoid protein loss and a possible error in the interpretation of results. Results of this study could also serve as the basis for further investigations on adjusting the skimming conditions for caprine milk in industrial dairy processing environment.

  6. 21 CFR 133.158 - Low-moisture part-skim mozzarella and scamorza cheese.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... cheese. 133.158 Section 133.158 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CHEESES AND RELATED CHEESE PRODUCTS Requirements for Specific Standardized Cheese and Related Products § 133.158 Low-moisture part-skim mozzarella and...

  7. 21 CFR 133.158 - Low-moisture part-skim mozzarella and scamorza cheese.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... cheese. 133.158 Section 133.158 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CHEESES AND RELATED CHEESE PRODUCTS Requirements for Specific Standardized Cheese and Related Products § 133.158 Low-moisture part-skim mozzarella and...

  8. On Mathematicians' Proof Skimming: A Reply to Inglis and Alcock

    ERIC Educational Resources Information Center

    Weber, Keith; Mejia-Ramos, Juan Pablo

    2013-01-01

    n a recent article, Inglis and Alcock (2012) contended that their data challenge the claim that when mathematicians validate proofs, they initially skim a proof to grasp its main idea before reading individual parts of the proof more carefully. This result is based on the fact that when mathematicians read proofs in their study, on average their…

  9. Effect of colostrum on gravity separation of milk somatic cells in skim milk.

    PubMed

    Geer, S R; Barbano, D M

    2014-02-01

    Our objective was to determine if immunoglobulins play a role in the gravity separation (rising to the top) of somatic cells (SC) in skim milk. Other researchers have shown that gravity separation of milk fat globules is enhanced by IgM. Our recent research found that bacteria and SC gravity separate in both raw whole and skim milk and that heating milk to >76.9 °C for 25s stopped gravity separation of milk fat, SC, and bacteria. Bovine colostrum is a good natural source of immunoglobulins. An experiment was designed where skim milk was heated at high temperatures (76 °C for 7 min) to stop the gravity separation of SC and then colostrum was added back to try to restore the gravity separation of SC in increments to achieve 0, 0.4, 0.8, 2.0, and 4.0 g/L of added immunoglobulins. The milk was allowed to gravity separate for 22 h at 4 °C. The heat treatment of skim milk was sufficient to stop the gravity separation of SC. The treatment of 4.0 g/L of added immunoglobulins was successful in restoring the gravity separation of SC as compared with raw skim milk. Preliminary spore data on the third replicate suggested that bacterial spores gravity separate the same way as the SC in heated skim milk and heated skim milk with 4.0 g/L of added immunoglobulins. Strong evidence exists that immunoglobulins are at least one of the factors necessary for the gravity separation of SC and bacterial spores. It is uncertain at this time whether SC are a necessary component for gravity separation of fat, bacteria, and spores to occur. Further research is needed to determine separately the role of immunoglobulins and SC in gravity separation of bacteria and spores. Understanding the mechanism of gravity separation may allow the development of a continuous flow technology to remove SC, bacteria, and spores from milk. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  10. Cerebrospinal fluid tau proteins in status epilepticus.

    PubMed

    Monti, Giulia; Tondelli, Manuela; Giovannini, Giada; Bedin, Roberta; Nichelli, Paolo F; Trenti, Tommaso; Meletti, Stefano; Chiari, Annalisa

    2015-08-01

    Tau protein is a phosphorylated microtubule-associated protein, principally localized at neuronal level in the central nervous system (CNS). Tau levels in the cerebrospinal fluid (CSF) are considered to index both axonal and neuronal damage. To date, however, no study has specifically evaluated the CSF levels of tau proteins in patients with status epilepticus (SE). We evaluated these established biomarkers of neuronal damage in patients with SE who received a lumbar puncture during SE between 2007 and 2014. Status epilepticus cases due to acute structural brain damage, including CNS infection, were excluded. Clinical, biological, therapeutic, and follow-up data were collected. Group comparison between patients stratified according to SE response to antiepileptic drugs (AEDs), disability, and epilepsy outcomes were performed. Twenty-eight patients were considered for the analyses (mean age 56 years): 14 patients had abnormally high CSF t-tau level, six patients had abnormally high CSF p-tau level, and only three patients had abnormally low Aβ1-42 level. Cerebrospinal fluid t-tau value was higher in patients who developed a refractory SE compared to patients with seizures controlled by AED. Cerebrospinal fluid t-tau values were positively correlated with SE duration and were higher in patients treated with propofol anesthesia compared to patients that had not received this treatment. Patients with higher CSF t-tau had higher risk of developing disability (OR = 32.5, p = 0.004) and chronic epilepsy (OR = 12; p = 0.016) in comparison with patients with lower CSF t-tau level. Our results suggest that CSF t-tau level might be proposed as a biomarker of SE severity and prognosis. Prospective studies are needed to evaluate the effects of propofol on tau pathology in this setting. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.

  11. RNA stores tau reversibly in complex coacervates.

    PubMed

    Zhang, Xuemei; Lin, Yanxian; Eschmann, Neil A; Zhou, Hongjun; Rauch, Jennifer N; Hernandez, Israel; Guzman, Elmer; Kosik, Kenneth S; Han, Songi

    2017-07-01

    Nonmembrane-bound organelles that behave like liquid droplets are widespread among eukaryotic cells. Their dysregulation appears to be a critical step in several neurodegenerative conditions. Here, we report that tau protein, the primary constituent of Alzheimer neurofibrillary tangles, can form liquid droplets and therefore has the necessary biophysical properties to undergo liquid-liquid phase separation (LLPS) in cells. Consonant with the factors that induce LLPS, tau is an intrinsically disordered protein that complexes with RNA to form droplets. Uniquely, the pool of RNAs to which tau binds in living cells are tRNAs. This phase state of tau is held in an approximately 1:1 charge balance across the protein and the nucleic acid constituents, and can thus be maximal at different RNA:tau mass ratios, depending on the biopolymer constituents involved. This feature is characteristic of complex coacervation. We furthermore show that the LLPS process is directly and sensitively tuned by salt concentration and temperature, implying it is modulated by both electrostatic interactions between the involved protein and nucleic acid constituents, as well as net changes in entropy. Despite the high protein concentration within the complex coacervate phase, tau is locally freely tumbling and capable of diffusing through the droplet interior. In fact, tau in the condensed phase state does not reveal any immediate changes in local protein packing, local conformations and local protein dynamics from that of tau in the dilute solution state. In contrast, the population of aggregation-prone tau as induced by the complexation with heparin is accompanied by large changes in local tau conformations and irreversible aggregation. However, prolonged residency within the droplet state eventually results in the emergence of detectable β-sheet structures according to thioflavin-T assay. These findings suggest that the droplet state can incubate tau and predispose the protein toward the

  12. RNA stores tau reversibly in complex coacervates

    PubMed Central

    Lin, Yanxian; Eschmann, Neil A.; Zhou, Hongjun; Rauch, Jennifer N.; Hernandez, Israel; Guzman, Elmer; Kosik, Kenneth S.; Han, Songi

    2017-01-01

    Nonmembrane-bound organelles that behave like liquid droplets are widespread among eukaryotic cells. Their dysregulation appears to be a critical step in several neurodegenerative conditions. Here, we report that tau protein, the primary constituent of Alzheimer neurofibrillary tangles, can form liquid droplets and therefore has the necessary biophysical properties to undergo liquid-liquid phase separation (LLPS) in cells. Consonant with the factors that induce LLPS, tau is an intrinsically disordered protein that complexes with RNA to form droplets. Uniquely, the pool of RNAs to which tau binds in living cells are tRNAs. This phase state of tau is held in an approximately 1:1 charge balance across the protein and the nucleic acid constituents, and can thus be maximal at different RNA:tau mass ratios, depending on the biopolymer constituents involved. This feature is characteristic of complex coacervation. We furthermore show that the LLPS process is directly and sensitively tuned by salt concentration and temperature, implying it is modulated by both electrostatic interactions between the involved protein and nucleic acid constituents, as well as net changes in entropy. Despite the high protein concentration within the complex coacervate phase, tau is locally freely tumbling and capable of diffusing through the droplet interior. In fact, tau in the condensed phase state does not reveal any immediate changes in local protein packing, local conformations and local protein dynamics from that of tau in the dilute solution state. In contrast, the population of aggregation-prone tau as induced by the complexation with heparin is accompanied by large changes in local tau conformations and irreversible aggregation. However, prolonged residency within the droplet state eventually results in the emergence of detectable β-sheet structures according to thioflavin-T assay. These findings suggest that the droplet state can incubate tau and predispose the protein toward the

  13. Phosphorylation of tau is regulated by PKN.

    PubMed

    Taniguchi, T; Kawamata, T; Mukai, H; Hasegawa, H; Isagawa, T; Yasuda, M; Hashimoto, T; Terashima, A; Nakai, M; Mori, H; Ono, Y; Tanaka, C

    2001-03-30

    For the phosphorylation state of microtubule-associated protein, tau plays a pivotal role in regulating microtubule networks in neurons. Tau promotes the assembly and stabilization of microtubules. The potential for tau to bind to microtubules is down-regulated after local phosphorylation. When we investigated the effects of PKN activation on tau phosphorylation, we found that PKN triggers disruption of the microtubule array both in vitro and in vivo and predominantly phosphorylates tau in microtubule binding domains (MBDs). PKN has a catalytic domain highly homologous to protein kinase C (PKC), a kinase that phosphorylates Ser-313 (= Ser-324, the number used in this study) in MBDs. Thus, we identified the phosphorylation sites of PKN and PKC subtypes (PKC-alpha, -betaI, -betaII, -gamma, -delta, -epsilon, -zeta, and -lambda) in MBDs. PKN phosphorylates Ser-258, Ser-320, and Ser-352, although all PKC subtypes phosphorylate Ser-258, Ser-293, Ser-324, and Ser-352. There is a PKN-specific phosphorylation site, Ser-320, in MBDs. HIA3, a novel phosphorylation-dependent antibody recognizing phosphorylated tau at Ser-320, showed immunoreactivity in Chinese hamster ovary cells expressing tau and the active form of PKN, but not in Chinese hamster ovary cells expressing tau and the inactive form of PKN. The immunoreactivity for phosphorylated tau at Ser-320 increased in the presence of a phosphatase inhibitor, FK506 treatment, which means that calcineurin (protein phosphatase 2B) may be involved in dephosphorylating tau at Ser-320 site. We also noted that PKN reduces the phosphorylation recognized by the phosphorylation-dependent antibodies AT8, AT180, and AT270 in vivo. Thus PKN serves as a regulator of microtubules by specific phosphorylation of tau, which leads to disruption of tubulin assembly.

  14. The Search for B+ to Tau+ Nu(Tau) at BaBar

    SciTech Connect

    Corwin, L.A.; /SLAC

    2007-01-08

    We present a search for the decay B{sup +} {yields} {tau}{sup +}{nu}{sub {tau}} using 288 fb{sup -1} of data collected at the {Upsilon}(4S) resonance with the BABAR detector at the SLAC PEP-II B-Factory. A sample of events with one reconstructed semileptonic B decay (B{sup -} {yields} D{sup o}{ell}{sup -}{bar {nu}}{sub {ell}}X) is selected, and in the recoil a search for B{sup +} {yields} {tau}{sup +}{nu}{sub {tau}} signal is performed. The {tau} is identified in the following channels: {tau}{sup +} {yields} e{sup +}{nu}{sub e}{bar {nu}}{sub {tau}}, {tau}{sup +} {yields} {mu}{sup +} {nu}{sub {mu}}{bar {nu}}{sub {tau}}, {tau}{sup +} {yields} {pi}{sup +}{pi}{sup 0}{bar {nu}}{sub {tau}}. We measure a branching fraction of {Beta}(B{sup +} {yields} {tau}{sup +}{nu}{sub {tau}}) = 0.88{sub -0.67}{sup +0.68}(stat.) {+-} 0.11(syst.) x 10{sup -4} and extract an upper limit on the branching fraction, at the 90% confidence level, of {Beta}(B{sup +} {yields} {tau}{sup +}{nu}{sub {tau}}) < 1.8 x 10{sup -4}. We calculate the product of the B meson decay constant and |V{sub ub}| to be f{sub B} {center_dot} |V{sub ub}| = (7.0{sub -3.6}{sup +2.3}(stat.){sub -0.5}{sup +0.4}(syst.)) x 10{sup -4} GeV.

  15. Selected Topics in Tau Physics from BaBar

    SciTech Connect

    Paramesvaran, S.; /Royal Holloway, U. of London

    2012-04-06

    Selected results from {tau} analyses performed using the BABAR detector at the SLAC National Accelerator Laboratory are presented. A precise measurement of the {tau} mass and the {tau}{sup +}{tau}{sup -} mass difference is undertaken using the hadronic decay mode {tau}{sup {+-}} {yields} {pi}{sup +}{pi}{sup -}{pi}{sup {+-}}{nu}{sub {tau}}. In addition an investigation into the strange decay modes {tau}{sup -} {yields} K{sub S}{sup 0}{pi}{sup -}{pi}{sup 0}{nu}{sub {tau}} and {tau}{sup -} {yields} K{sub S}{sup 0}{pi}{sup -}{nu}{sub {tau}} is also presented, including a fit to the {tau}{sup -} {yields} K{sub S}{sup 0}{pi}{sup -}{nu}{sub {tau}} invariant mass spectrum. Precise values for M(K*(892)) and {Lambda}(K*(892)) are obtained.

  16. Prospect for measuring the CP phase in the $$h\\tau\\tau$$ coupling at the LHC

    DOE PAGES

    Askew, Andrew; Jaiswal, Prerit; Okui, Takemichi; ...

    2015-04-01

    The search for a new source of CP violation is one of the most important endeavors in particle physics. A particularly interesting way to perform this search is to probe the CP phase in themore » $$h\\tau\\tau$$ coupling, as the phase is currently completely unconstrained by all existing data. Recently, a novel variable $$\\Theta$$ was proposed for measuring the CP phase in the $$h\\tau\\tau$$ coupling through the $$\\tau^\\pm \\to \\pi^\\pm \\pi^0 \

  17. Measurement of the Semileptonic Decays B->D tau nu and B->D* tau nu

    SciTech Connect

    Aubert, : B.

    2009-02-23

    The authors present measurements of the semileptonic decays B{sup -} {yields} D{sup 0} {tau}{sup -} {bar {nu}}{sub {tau}}, B{sup -} {yields} D*{sup 0} {tau}{sup -}{bar {nu}}{sub {tau}}, {bar B}{sup 0} {yields} D{sup +} {tau}{sup -} {bar {nu}}{sub {tau}}, and {bar B}{sup 0} {yields} D*{sup +} {tau}{sup -}{bar {nu}}{sub {tau}}, which are sensitive to non-Standard Model amplitudes in certain scenarios. The data sample consists of 232 x 10{sup 6} {Upsilon}(4S) {yields} B{bar B} decays collected with the BABAR detector at the PEP-II e{sup +}e{sup -} collider. They select events with a D or D* meson and a light lepton ({ell} = e or {mu}) recoiling against a fully reconstructed B meson. They perform a fit to the joint distribution of lepton momentum and missing mass squared to distinguish signal B {yields} D{sup (*)}{tau}{sup -} {bar {nu}}{sub {tau}} ({tau}{sup -} {yields} {ell}{sup -} {bar {nu}}{sub {ell}}{nu}{sub {tau}}) events from the backgrounds, predominantly B {yields} D{sup (*)} {ell}{sup -}{bar {nu}}{sub {ell}}. They measure the branching-fraction ratios R(D) {triple_bond} {Beta}(B {yields} D{tau}{sup -} {bar {nu}}{sub {tau}})/{Beta}(B {yields} D{ell}{sup -} {bar {nu}}{sub {ell}}) and R(D*) {triple_bond} {Beta}(B {yields} D*{tau}{sup -} {bar {nu}}{sub {tau}})/{Beta}(B {yields} D* {ell}{sup -} {bar {nu}}{sub {ell}}) and, from a combined fit to B{sup -} and {bar B}{sup 0} channels, obtain the results R(D) = (41.6 {+-} 11.7 {+-} 5.2)% and R(D*) = (29.7 {+-} 5.6 {+-} 1.8)%, where the uncertainties are statistical and systematic. Normalizing to measured B{sup -} {yields} D{sup (*)0} {ell}{sup -} {bar {nu}}{sub {ell}} branching fractions, they obtain {Beta}(B {yields} D{tau}{sup -} {bar {nu}}{sub {tau}}) = (0.86 {+-} 0.24 {+-} 0.11 {+-} 0.06)% and {Beta}(B {yields} D*{tau}{sup -} {bar {nu}}{sub {tau}}) = (1.62 {+-} 0.31 {+-} 0.10 {+-} 0.05)%, where the additional third uncertainty is from the normalization mode. They also present, for the first time, distributions of

  18. Exclusive branching-fraction measurements of semileptonic tau decays into three charged hadrons, into phipi(-)nu tau, and into phi K(-)nu tau.

    PubMed

    Aubert, B; Bona, M; Boutigny, D; Couderc, F; Karyotakis, Y; Lees, J P; Poireau, V; Tisserand, V; Zghiche, A; Grauges, E; Palano, A; Chen, J C; Qi, N D; Rong, G; Wang, P; Zhu, Y S; Eigen, G; Ofte, I; Stugu, B; Abrams, G S; Battaglia, M; Brown, D N; Button-Shafer, J; Cahn, R N; Charles, E; Gill, M S; Groysman, Y; Jacobsen, R G; Kadyk, J A; Kerth, L T; Kolomensky, Yu G; Kukartsev, G; Pegna, D Lopes; Lynch, G; Mir, L M; Orimoto, T J; Pripstein, M; Roe, N A; Ronan, M T; Wenzel, W A; del Amo Sanchez, P; Barrett, M; Ford, K E; Harrison, T J; Hart, A J; Hawkes, C M; Watson, A T; Held, T; Koch, H; Lewandowski, B; Pelizaeus, M; Peters, K; Schroeder, T; Steinke, M; Boyd, J T; Burke, J P; Cottingham, W N; Walker, D; Asgeirsson, D J; Cuhadar-Donszelmann, T; Fulsom, B G; Hearty, C; Knecht, N S; Mattison, T S; McKenna, J A; Khan, A; Kyberd, P; Saleem, M; Sherwood, D J; Teodorescu, L; Blinov, V E; Bukin, A D; Druzhinin, V P; Golubev, V B; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Todyshev, K Yu; Best, D S; Bondioli, M; Bruinsma, M; Chao, M; Curry, S; Eschrich, I; Kirkby, D; Lankford, A J; Lund, P; Mandelkern, M; Roethel, W; Stoker, D P; Abachi, S; Buchanan, C; Foulkes, S D; Gary, J W; Long, O; Shen, B C; Wang, K; Zhang, L; Hadavand, H K; Hill, E J; Paar, H P; Rahatlou, S; Sharma, V; Berryhill, J W; Campagnari, C; Cunha, A; Dahmes, B; Hong, T M; Kovalskyi, D; Richman, J D; Beck, T W; Eisner, A M; Flacco, C J; Heusch, C A; Kroseberg, J; Lockman, W S; Nesom, G; Schalk, T; Schumm, B A; Seiden, A; Spradlin, P; Williams, D C; Wilson, M G; Albert, J; Chen, E; Cheng, C H; Dvoretskii, A; Fang, F; Hitlin, D G; Narsky, I; Piatenko, T; Porter, F C; Mancinelli, G; Meadows, B T; Mishra, K; Sokoloff, M D; Blanc, F; Bloom, P C; Chen, S; Ford, W T; Hirschauer, J F; Kreisel, A; Nagel, M; Nauenberg, U; Olivas, A; Ruddick, W O; Smith, J G; Ulmer, K A; Wagner, S R; Zhang, J; Chen, A; Eckhart, E A; Soffer, A; Toki, W H; Wilson, R J; Winklmeier, F; Zeng, Q; Altenburg, D D; Feltresi, E; Hauke, A; Jasper, H; Merkel, J; Petzold, A; Spaan, B; Brandt, T; Klose, V; Lacker, H M; Mader, W F; Nogowski, R; Schubert, J; Schubert, K R; Schwierz, R; Sundermann, J E; Volk, A; Bernard, D; Bonneaud, G R; Latour, E; Thiebaux, Ch; Verderi, M; Clark, P J; Gradl, W; Muheim, F; Playfer, S; Robertson, A I; Xie, Y; Andreotti, M; Bettoni, D; Bozzi, C; Calabrese, R; Cibinetto, G; Luppi, E; Negrini, M; Petrella, A; Piemontese, L; Prencipe, E; Anulli, F; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Finocchiaro, G; Pacetti, S; Patteri, P; Peruzzi, I M; Piccolo, M; Rama, M; Zallo, A; Buzzo, A; Contri, R; Lo Vetere, M; Macri, M M; Monge, M R; Passaggio, S; Patrignani, C; Robutti, E; Santroni, A; Tosi, S; Brandenburg, G; Chaisanguanthum, K S; Lee, C L; Morii, M; Wu, J; Dubitzky, R S; Marks, J; Schenk, S; Uwer, U; Bard, D J; Bhimji, W; Bowerman, D A; Dauncey, P D; Egede, U; Flack, R L; Nash, J A; Nikolich, M B; Vazquez, W Panduro; Behera, P K; Chai, X; Charles, M J; Mallik, U; Meyer, N T; Ziegler, V; Cochran, J; Crawley, H B; Dong, L; Eyges, V; Meyer, W T; Prell, S; Rosenberg, E I; Rubin, A E; Gritsan, A V; Denig, A G; Fritsch, M; Schott, G; Arnaud, N; Davier, M; Grosdidier, G; Höcker, A; Lepeltier, V; Le Diberder, F; Lutz, A M; Oyanguren, A; Pruvot, S; Rodier, S; Roudeau, P; Schune, M H; Serrano, J; Stocchi, A; Wang, W F; Wormser, G; Lange, D J; Wright, D M; Chavez, C A; Forster, I J; Fry, J R; Gabathuler, E; Gamet, R; George, K A; Hutchcroft, D E; Payne, D J; Schofield, K C; Touramanis, C; Bevan, A J; Clarke, C K; Di Lodovico, F; Menges, W; Sacco, R; Cowan, G; Flaecher, H U; Hopkins, D A; Jackson, P S; McMahon, T R; Salvatore, F; Wren, A C; Brown, D N; Davis, C L; Allison, J; Barlow, N R; Barlow, R J; Chia, Y M; Edgar, C L; Lafferty, G D; Naisbit, M T; Williams, J C; Yi, J I; Chen, C; Hulsbergen, W D; Jawahery, A; Lae, C K; Roberts, D A; Simi, G; Blaylock, G; Dallapiccola, C; Hertzbach, S S; Li, X; Moore, T B; Saremi, S; Staengle, H; Cowan, R; Sciolla, G; Sekula, S J; Spitznagel, M; Taylor, F; Yamamoto, R K; Kim, H; McLachlin, S E; Patel, P M; Robertson, S H; Lazzaro, A; Lombardo, V; Palombo, F; Bauer, J M; Cremaldi, L; Eschenburg, V; Godang, R; Kroeger, R; Sanders, D A; Summers, D J; Zhao, H W; Brunet, S; Côté, D; Simard, M; Taras, P; Viaud, F B; Nicholson, H; Cavallo, N; De Nardo, G; Fabozzi, F; Gatto, C; Lista, L; Monorchio, D; Paolucci, P; Piccolo, D; Sciacca, C; Baak, M A; Raven, G; Snoek, H L; Jessop, C P; LoSecco, J M; Benelli, G; Corwin, L A; Gan, K K; Honscheid, K; Hufnagel, D; Jackson, P D; Kagan, H; Kass, R; Rahimi, A M; Regensburger, J J; Ter-Antonyan, R; Wong, Q K; Blount, N L; Brau, J; Frey, R; Igonkina, O; Kolb, J A; Lu, M; Potter, C T; Rahmat, R; Sinev, N B; Strom, D; Strube, J; Torrence, E; Gaz, A; Margoni, M; Morandin, M; Pompili, A; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Voci, C; Benayoun, M; Briand, H; Chauveau, J; David, P; Del Buono, L; de la Vaissière, Ch; Hamon, O; Hartfiel, B L; Leruste, Ph; Malclès, J; Ocariz, J; Roos, L; Therin, G; Gladney, L; Biasini, M; Covarelli, R; Angelini, C; Batignani, G; Bettarini, S; Bucci, F; Calderini, G; Carpinelli, M; Cenci, R; Forti, F; Giorgi, M A; Lusiani, A; Marchiori, G; Mazur, M A; Morganti, M; Neri, N; Paoloni, E; Rizzo, G; Walsh, J J; Haire, M; Judd, D; Wagoner, D E; Biesiada, J; Danielson, N; Elmer, P; Lau, Y P; Lu, C; Olsen, J; Smith, A J S; Telnov, A V; Bellini, F; Cavoto, G; D'Orazio, A; del Re, D; Di Marco, E; Faccini, R; Ferrarotto, F; Ferroni, F; Gaspero, M; Gioi, L Li; Mazzoni, M A; Morganti, S; Piredda, G; Polci, F; Tehrani, F Safai; Voena, C; Ebert, M; Schröder, H; Waldi, R; Adye, T; Franek, B; Olaiya, E O; Ricciardi, S; Wilson, F F; Aleksan, R; Emery, S; Gaidot, A; Ganzhur, S F; de Monchenault, G Hamel; Kozanecki, W; Legendre, M; Vasseur, G; Yèche, Ch; Zito, M; Chen, X R; Liu, H; Park, W; Purohit, M V; Wilson, J R; Allen, M T; Aston, D; Bartoldus, R; Bechtle, P; Berger, N; Claus, R; Coleman, J P; Convery, M R; Dingfelder, J C; Dorfan, J; Dubois-Felsmann, G P; Dujmic, D; Dunwoodie, W; Field, R C; Glanzman, T; Gowdy, S J; Graham, M T; Grenier, P; Halyo, V; Hast, C; Hryn'ova, T; Innes, W R; Kelsey, M H; Kim, P; Leith, D W G S; Li, S; Luitz, S; Luth, V; Lynch, H L; MacFarlane, D B; Marsiske, H; Messner, R; Muller, D R; O'Grady, C P; Ozcan, V E; Perazzo, A; Perl, M; Pulliam, T; Ratcliff, B N; Roodman, A; Salnikov, A A; Schindler, R H; Schwiening, J; Snyder, A; Stelzer, J; Su, D; Sullivan, M K; Suzuki, K; Swain, S K; Thompson, J M; Va'vra, J; van Bakel, N; Wagner, A P; Weaver, M; Weinstein, A J R; Wisniewski, W J; Wittgen, M; Wright, D H; Wulsin, H W; Yarritu, A K; Yi, K; Young, C C; Burchat, P R; Edwards, A J; Majewski, S A; Petersen, B A; Wilden, L; Ahmed, S; Alam, M S; Bula, R; Ernst, J A; Jain, V; Pan, B; Saeed, M A; Wappler, F R; Zain, S B; Bugg, W; Krishnamurthy, M; Spanier, S M; Eckmann, R; Ritchie, J L; Satpathy, A; Schilling, C J; Schwitters, R F; Izen, J M; Lou, X C; Ye, S; Bianchi, F; Gallo, F; Gamba, D; Bomben, M; Bosisio, L; Cartaro, C; Cossutti, F; Della Ricca, G; Dittongo, S; Lanceri, L; Vitale, L; Azzolini, V; Lopez-March, N; Martinez-Vidal, F; Banerjee, Sw; Bhuyan, B; Brown, C M; Fortin, D; Hamano, K; Kowalewski, R; Nugent, I M; Roney, J M; Sobie, R J; Back, J J; Harrison, P F; Latham, T E; Mohanty, G B; Pappagallo, M; Band, H R; Chen, X; Cheng, B; Dasu, S; Datta, M; Flood, K T; Hollar, J J; Kutter, P E; Mellado, B; Mihalyi, A; Pan, Y; Pierini, M; Prepost, R; Wu, S L; Yu, Z; Neal, H

    2008-01-11

    Using a data sample corresponding to an integrated luminosity of 342 fb(-1) collected with the BABAR detector at the SLAC PEP-II electron-positron storage ring operating at a center-of-mass energy near 10.58 GeV, we measure B(tau(-)--> pi(-)pi(-)pi+nu(tau)(ex.K(S0))=(8.83+/-0.01+/-0.13)%, B(tau(-) -->K(-)pi(-)pi+nu tau(ex.K(S0))=(0.273+/-0.002+/-0.009)%, B(tau(-) -->K(-)pi(-)K+nu tau)=(0.1346+/-0.0010+/-0.0036)%, and B(tau(-) -->K(-)K(-)K+nu tau)=(1.58+/-0.13+/-0.12)x10;{-5}, where the uncertainties are statistical and systematic, respectively. These include significant improvements over previous measurements and a first measurement of B(tau(-) -->K(-)K(-)K+nu tau) in which no resonance structure is assumed. We also report a first measurement of B(tau(-) -->var phi(-)nu tau)=(3.42+/-0.55+/-0.25)x10(-5), a new measurement of B(tau(-) -->var phi K(-)nu tau)=(3.39+/-0.20+/-0.28)x10(-5) and a first upper limit on B(tau(-) -->K(-)K(-)K+nu tau(ex.var phi)).

  19. New Features about Tau Function and Dysfunction

    PubMed Central

    Medina, Miguel; Hernández, Félix; Avila, Jesús

    2016-01-01

    Tau is a brain microtubule-associated protein that directly binds to a microtubule and dynamically regulates its structure and function. Under pathological conditions, tau self-assembles into filamentous structures that end up forming neurofibrillary tangles. Prominent tau neurofibrillary pathology is a common feature in a number of neurodegenerative disorders, collectively referred to as tauopathies, the most common of which is Alzheimer’s disease (AD). Beyond its classical role as a microtubule-associated protein, recent advances in our understanding of tau cellular functions have revealed novel insights into their important role during pathogenesis and provided potential novel therapeutic targets. Regulation of tau behavior and function under physiological and pathological conditions is mainly achieved through post-translational modifications, including phosphorylation, glycosylation, acetylation, and truncation, among others, indicating the complexity and variability of factors influencing regulation of tau toxicity, all of which have significant implications for the development of novel therapeutic approaches in various neurodegenerative disorders. A more comprehensive understanding of the molecular mechanisms regulating tau function and dysfunction will provide us with a better outline of tau cellular networking and, hopefully, offer new clues for designing more efficient approaches to tackle tauopathies in the near future. PMID:27104579

  20. Physics with tau leptons at CDF

    SciTech Connect

    Hays, C.P.; /Oxford U.

    2007-04-01

    The {radical}s = 1.96 TeV p{bar p} collisions produced by the Tevatron result in many processes with tau leptons in the final state. The CDF Collaboration has studied these final states in Z and t{bar t} production, and has used tau leptons to search for evidence of Higgs, sparticle, and Z{prime} production.

  1. Determination of the Michel Parameters and the tau Neutrino Helicity in tau Decay

    SciTech Connect

    Jessop, Colin P.

    2003-05-07

    Using the CLEO II detector at the e{sup +}e{sup -} storage ring CESR, we have determined the Michel parameters {rho}, {zeta}, and {delta} in {tau}{sup {-+}}{nu}{bar {nu}} decay as well as the {tau} neutrino helicity parameter H{sub {nu}{sub {tau}}} in {tau}{sup {-+}}{pi}{sup 0}{nu} decay. From a data sample of 3.02 x 10{sup 6} {tau} pairs produced at {radical}s = 10.6 GeV, using events of the topology e{sup +}e{sup -} {yields} {tau}{sup +}{tau}{sup -} {yields} (l{sup {+-}}{nu}{bar {nu}})({pi}{sup {-+}}{pi}{sup 0}{nu}) and e{sup +}e{sup -} {yields} {tau}{sup +}{tau}{sup -} {yields} ({pi}{sup {+-}}{pi}{sup 0}{bar {nu}})({pi}{sup {-+}}{pi}{sup 0}{nu}), and the determined sign of h{sub {nu}{sub {tau}}} [1,2], the combined result of the three samples is: {rho} = 0.747 {+-} 0.010 {+-} 0.006, {zeta} = 1.007 {+-} 0.040 {+-} 0.015, {zeta}{delta} = 0.745 {+-}0.026 {+-}0.009, and h{sub {nu}{sub {tau}}} = -0.995 {+-} 0.010 {+-} 0.003. The results are in agreement with the Standard Model V-A interaction.

  2. Intrinsic Tau Acetylation Is Coupled to Auto-Proteolytic Tau Fragmentation.

    PubMed

    Cohen, Todd J; Constance, Brian H; Hwang, Andrew W; James, Michael; Yuan, Chao-Xing

    2016-01-01

    Tau proteins are abnormally aggregated in a range of neurodegenerative tauopathies including Alzheimer's disease (AD). Recently, tau has emerged as an extensively post-translationally modified protein, among which lysine acetylation is critical for normal tau function and its pathological aggregation. Here, we demonstrate that tau isoforms have different propensities to undergo lysine acetylation, with auto-acetylation occurring more prominently within the lysine-rich microtubule-binding repeats. Unexpectedly, we identified a unique intrinsic property of tau in which auto-acetylation induces proteolytic tau cleavage, thereby generating distinct N- and C-terminal tau fragments. Supporting a catalytic reaction-based mechanism, mapping and mutagenesis studies showed that tau cysteines, which are required for acetyl group transfer, are also essential for auto-proteolytic tau processing. Further mass spectrometry analysis identified the C-terminal 2nd and 4th microtubule binding repeats as potential sites of auto-cleavage. The identification of acetylation-mediated auto-proteolysis provides a new biochemical mechanism for tau self-regulation and warrants further investigation into whether auto-catalytic functions of tau are implicated in AD and other tauopathies.

  3. Intrinsic Tau Acetylation Is Coupled to Auto-Proteolytic Tau Fragmentation

    PubMed Central

    Cohen, Todd J.; Constance, Brian H.; Hwang, Andrew W.; James, Michael; Yuan, Chao-Xing

    2016-01-01

    Tau proteins are abnormally aggregated in a range of neurodegenerative tauopathies including Alzheimer’s disease (AD). Recently, tau has emerged as an extensively post-translationally modified protein, among which lysine acetylation is critical for normal tau function and its pathological aggregation. Here, we demonstrate that tau isoforms have different propensities to undergo lysine acetylation, with auto-acetylation occurring more prominently within the lysine-rich microtubule-binding repeats. Unexpectedly, we identified a unique intrinsic property of tau in which auto-acetylation induces proteolytic tau cleavage, thereby generating distinct N- and C-terminal tau fragments. Supporting a catalytic reaction-based mechanism, mapping and mutagenesis studies showed that tau cysteines, which are required for acetyl group transfer, are also essential for auto-proteolytic tau processing. Further mass spectrometry analysis identified the C-terminal 2nd and 4th microtubule binding repeats as potential sites of auto-cleavage. The identification of acetylation-mediated auto-proteolysis provides a new biochemical mechanism for tau self-regulation and warrants further investigation into whether auto-catalytic functions of tau are implicated in AD and other tauopathies. PMID:27383765

  4. Microglial internalization and degradation of pathological tau is enhanced by an anti-tau monoclonal antibody

    PubMed Central

    Luo, Wenjie; Liu, Wencheng; Hu, Xiaoyan; Hanna, Mary; Caravaca, April; Paul, Steven M.

    2015-01-01

    Microglia have been shown to contribute to the clearance of brain amyloid β peptides (Aβ), the major component of amyloid plaques, in Alzheimer’s disease (AD). However, it is not known whether microglia play a similar role in the clearance of tau, the major component of neurofibrillary tangles (NFTs). We now report that murine microglia rapidly internalize and degrade hyperphosphorylated pathological tau isolated from AD brain tissue in a time-dependent manner in vitro. We further demonstrate that microglia readily degrade human tau species released from AD brain sections and eliminate NFTs from brain sections of P301S tauopathy mice. The anti-tau monoclonal antibody MC1 enhances microglia-mediated tau degradation in an Fc-dependent manner. Our data identify a potential role for microglia in the degradation and clearance of pathological tau species in brain and provide a mechanism explaining the potential therapeutic actions of passively administered anti-tau monoclonal antibodies. PMID:26057852

  5. [Present and future of the tau dementia therapy].

    PubMed

    Takashima, Akihiko

    2013-01-01

    Neurofibrillarly tangles (NFTs) are seen most patients, who shows dementia, while β amyloid deposition observed specifically in AD patients. NFTs observe first from coeruleus and entorhinal cortex, and then spread to neocortex, which well explain clinical progression of AD, such as memory problem to dementia. Tau fibrils are the major component of NFT. Before forming tau fibrils, tau binds together, form soluble tau oligomer, and then granular tau oligomer. The soluble tau oligomer associates with synapse loss, and granular tau formation induces neuronal loss. Therefore, tau aggregation inhibitor is expected to halt the clinical progression of AD.

  6. Tau phosphorylation affects its axonal transport and degradation

    PubMed Central

    Rodríguez-Martín, Teresa; Cuchillo-Ibáñez, Inmaculada; Noble, Wendy; Nyenya, Fanon; Anderton, Brian H.; Hanger, Diane P.

    2013-01-01

    Phosphorylated forms of microtubule-associated protein tau accumulate in neurofibrillary tangles in Alzheimer's disease. To investigate the effects of specific phosphorylated tau residues on its function, wild type or phosphomutant tau was expressed in cells. Elevated tau phosphorylation decreased its microtubule binding and bundling, and increased the number of motile tau particles, without affecting axonal transport kinetics. In contrast, reducing tau phosphorylation enhanced the amount of tau bound to microtubules and inhibited axonal transport of tau. To determine whether differential tau clearance is responsible for the increase in phosphomimic tau, we inhibited autophagy in neurons which resulted in a 3-fold accumulation of phosphomimic tau compared with wild type tau, and endogenous tau was unaffected. In autophagy-deficient mouse embryonic fibroblasts, but not in neurons, proteasomal degradation of phosphomutant tau was also reduced compared with wild type tau. Therefore, autophagic and proteasomal pathways are involved in tau degradation, with autophagy appearing to be the primary route for clearing phosphorylated tau in neurons. Defective autophagy might contribute to the accumulaton of tau in neurodegenerative diseases. PMID:23601672

  7. Reduced number of axonal mitochondria and tau hypophosphorylation in mouse P301L tau knockin neurons.

    PubMed

    Rodríguez-Martín, Teresa; Pooler, Amy M; Lau, Dawn H W; Mórotz, Gábor M; De Vos, Kurt J; Gilley, Jonathan; Coleman, Michael P; Hanger, Diane P

    2016-01-01

    Expression of the frontotemporal dementia-related tau mutation, P301L, at physiological levels in adult mouse brain (KI-P301L mice) results in overt hypophosphorylation of tau and age-dependent alterations in axonal mitochondrial transport in peripheral nerves. To determine the effects of P301L tau expression in the central nervous system, we examined the kinetics of mitochondrial axonal transport and tau phosphorylation in primary cortical neurons from P301L knock-in (KI-P301L) mice. We observed a significant 50% reduction in the number of mitochondria in the axons of cortical neurons cultured from KI-P301L mice compared to wild-type neurons. Expression of murine P301L tau did not change the speed, direction of travel or likelihood of movement of mitochondria. Notably, the angle that defines the orientation of the mitochondria in the axon, and the volume of individual moving mitochondria, were significantly increased in neurons expressing P301L tau. We found that murine tau phosphorylation in KI-P301L mouse neurons was diminished and the ability of P301L tau to bind to microtubules was also reduced compared to tau in wild-type neurons. The P301L mutation did not influence the ability of murine tau to associate with membranes in cortical neurons or in adult mouse brain. We conclude that P301L tau is associated with mitochondrial changes and causes an early reduction in murine tau phosphorylation in neurons coupled with impaired microtubule binding of tau. These results support the association of mutant tau with detrimental effects on mitochondria and will be of significance for the pathogenesis of tauopathies.

  8. Ante mortem cerebrospinal fluid tau levels correlate with postmortem tau pathology in frontotemporal lobar degeneration.

    PubMed

    Irwin, David J; Lleó, Alberto; Xie, Sharon X; McMillan, Corey T; Wolk, David A; Lee, Edward B; Van Deerlin, Viviana M; Shaw, Leslie M; Trojanowski, John Q; Grossman, Murray

    2017-08-01

    To test the hypotheses that (1) antemortem cerebrospinal fluid (CSF) tau levels correlate with postmortem tau pathology in frontotemporal lobar degeneration (FTLD) and (2) tauopathy patients have higher phosphorylated-tau levels compared to transactivation response element DNA-binding protein 43 (TDP-43) proteinopathy patients while accounting for Alzheimer's disease (AD) copathology. Patients had autopsy-confirmed FTLD with tauopathy (n = 31), TDP-43 proteinopathy (n = 49), or AD (n = 26) with antemortem CSF. CSF tau levels were compared between groups and correlated with digital histology measurement of postmortem tau pathology averaged from three cerebral regions (angular gyrus, mid-frontal cortex, and anterior cingulate gyrus). Multivariate linear regression tested the association of ante mortem CSF tau levels with postmortem tau pathology adjusting for demographics. Multivariate regression found an independent association of ante mortem CSF phosphorylated tau levels with postmortem cerebral tau pathology in FTLD (Beta = 1.3; 95% confidence interval = 0.2-2.4; p < 0.02). After excluding patients with coincident AD-associated tau pathology accompanying sporadic FTLD, we found lower CSF phosphorylated tau levels in the TDP-43 group (median = 7.4pg/ml; interquartile range [IQR] = 6.0, 12.3; n = 26) compared to the tauopathy group (median = 12.5pg/ml; IQR = 10.7, 15.0; n = 23; Z = 2.6; p < 0.01). CSF phosphorylated-tau levels are positively associated with cerebral tau burden in FTLD. In vivo detection of AD copathology in sporadic FTLD patients may help stratify clinical cohorts with pure neuropathology in which low CSF phosphorylated-tau levels may have diagnostic utility to distinguish TDP-43 proteinopathy from tauopathy. Autopsy-confirmed samples are critical for FTLD biomarker development and validation. Ann Neurol 2017;82:247-258. © 2017 American Neurological Association.

  9. Glycan Determinants of Heparin-Tau Interaction.

    PubMed

    Zhao, Jing; Huvent, Isabelle; Lippens, Guy; Eliezer, David; Zhang, Anqiang; Li, Quanhong; Tessier, Peter; Linhardt, Robert J; Zhang, Fuming; Wang, Chunyu

    2017-03-14

    Tau aggregates into paired helical filaments within neurons, a pathological hallmark of Alzheimer's disease. Heparin promotes tau aggregation and recently has been shown to be involved in the cellular uptake of tau aggregates. Although the tau-heparin interaction has been extensively studied, little is known about the glycan determinants of this interaction. Here, we used surface plasmon resonance (SPR) and NMR spectroscopy to characterize the interaction between two tau fragments, K18 and K19, and several polysaccharides, including heparin, heparin oligosaccharides, chemically modified heparin, and related glycans. Using a heparin-immobilized chip, SPR revealed that tau K18 and K19 bind heparin with a KD of 0.2 and 70 μM, respectively. In SPR competition experiments, N-desulfation and 2-O-desulfation had no effect on heparin binding to K18, whereas 6-O-desulfation severely reduced binding, suggesting a critical role for 6-O-sulfation in the tau-heparin interaction. The tau-heparin interaction became stronger with longer-chain heparin oligosaccharides. As expected for an electrostatics-driven interaction, a moderate amount of salt (0.3 M NaCl) abolished binding. NMR showed the largest chemical-shift perturbation (CSP) in R2 in tau K18, which was absent in K19, revealing differential binding sites in K18 and K19 to heparin. Dermatan sulfate binding produced minimal CSP, whereas dermatan disulfate, with the additional 6-O-sulfo group, induced much larger CSP. 2-O-desulfated heparin induced much larger CSP in K18 than 6-O-desulfated heparin. Our data demonstrate a crucial role for the 6-O-sulfo group in the tau-heparin interaction, which to our knowledge has not been reported before.

  10. A Dual Pathogenic Mechanism Links Tau Acetylation to Sporadic Tauopathy

    PubMed Central

    Trzeciakiewicz, Hanna; Tseng, Jui-Heng; Wander, Connor M.; Madden, Victoria; Tripathy, Ashutosh; Yuan, Chao-Xing; Cohen, Todd J.

    2017-01-01

    Tau acetylation has recently emerged as a dominant post-translational modification (PTM) in Alzheimer’s disease (AD) and related tauopathies. Mass spectrometry studies indicate that tau acetylation sites cluster within the microtubule (MT)-binding region (MTBR), suggesting acetylation could regulate both normal and pathological tau functions. Here, we combined biochemical and cell-based approaches to uncover a dual pathogenic mechanism mediated by tau acetylation. We show that acetylation specifically at residues K280/K281 impairs tau-mediated MT stabilization, and enhances the formation of fibrillar tau aggregates, highlighting both loss and gain of tau function. Full-length acetylation-mimic tau showed increased propensity to undergo seed-dependent aggregation, revealing a potential role for tau acetylation in the propagation of tau pathology. We also demonstrate that methylene blue, a reported tau aggregation inhibitor, modulates tau acetylation, a novel mechanism of action for this class of compounds. Our study identifies a potential “two-hit” mechanism in which tau acetylation disengages tau from MTs and also promotes tau aggregation. Thus, therapeutic approaches to limit tau K280/K281 acetylation could simultaneously restore MT stability and ameliorate tau pathology in AD and related tauopathies. PMID:28287136

  11. The Dynamics and Turnover of Tau Aggregates in Cultured Cells

    PubMed Central

    Guo, Jing L.; Buist, Arjan; Soares, Alberto; Callaerts, Kathleen; Calafate, Sara; Stevenaert, Frederik; Daniels, Joshua P.; Zoll, Bryan E.; Crowe, Alex; Brunden, Kurt R.; Moechars, Diederik; Lee, Virginia M. Y.

    2016-01-01

    Filamentous tau aggregates, the hallmark lesions of Alzheimer disease (AD), play key roles in neurodegeneration. Activation of protein degradation systems has been proposed to be a potential strategy for removing pathological tau, but it remains unclear how effectively tau aggregates can be degraded by these systems. By applying our previously established cellular model system of AD-like tau aggregate induction using preformed tau fibrils, we demonstrate that tau aggregates induced in cells with regulated expression of full-length mutant tau can be gradually cleared when soluble tau expression is suppressed. This clearance is at least partially mediated by the autophagy-lysosome pathway, although both the ubiquitin-proteasome system and the autophagy-lysosome pathway are deficient in handling large tau aggregates. Importantly, residual tau aggregates left after the clearance phase leads to a rapid reinstatement of robust tau pathology once soluble tau expression is turned on again. Moreover, we succeeded in generating monoclonal cells persistently carrying tau aggregates without obvious cytotoxicity. Live imaging of GFP-tagged tau aggregates showed that tau inclusions are dynamic structures constantly undergoing “fission” and “fusion,” which facilitate stable propagation of tau pathology in dividing cells. These findings provide a greater understanding of cell-to-cell transmission of tau aggregates in dividing cells and possibly neurons. PMID:27129267

  12. Hadronic decays of the tau lepton : {tau}- {yields} ({pi}{pi}{pi})- {nu}{tau} within Resonance Chiral Theory

    SciTech Connect

    Gomez Dumm, D.; Pich, A.; Portoles, J.

    2006-01-12

    {tau} decays into hadrons foresee the study of the hadronization of vector and axial-vector QCD currents, yielding relevant information on the dynamics of the resonances entering into the processes. We analyse {tau} {yields} {pi}{pi}{pi}{nu}{tau} decays within the framework of the Resonance Chiral Theory, comparing this theoretical scheme with the experimental data, namely ALEPH spectral function and branching ratio. Hence we get values for the mass and on-shell width of the a 1 (1260) resonance, and provide the structure functions that have been measured by OPAL and CLEO-II.

  13. Cerebrospinal fluid levels of tau and phospho-tau-181 proteins during pregnancy.

    PubMed

    Lederer, Wolfgang; Dominguez, Cristina Alomar; Popovscaia, Marina; Putz, Günther; Humpel, Christian

    2016-10-01

    During pregnancy various interactions occur between structural alterations of the maternal brain and placental metabolism. The aim of the present study was to investigate whether cerebrospinal fluid concentrations of tau and phospho-tau-181 protein vary during normal pregnancy and in women with preeclampsia and HELLP syndrome. We measured cerebrospinal fluid biomarkers, tau and phospho-tau-181 protein levels in 90 pregnant women electively assigned for regional anaesthesia during pregnancy or for cesarean section using enzyme-linked immunosorbent assays. Cerebrospinal fluid concentrations for tau and phospho-tau-181 in 66 women with normal pregnancy were 308.5±117.3pg/mL and 50.5±16.7pg/mL, respectively. Blood pressure, liver function, clotting activity and kidney function were significantly different in eleven women with preeclampsia and HELLP syndrome. The weight of the newly born (p<0.001; HR: 0.998), the weight of the placenta (p=0.018) and concentrations for phospho-tau-181 (p=0.043; HR: 1.211) correlated significantly with the disease. Mean concentrations of cerebrospinal fluid tau and phospho-tau-181 protein during pregnancy were evaluated. Phospho-tau-181 protein concentrations correlated with placental function supporting the hypothesis that altered expression of neuronal factors during pregnancy may affect development of the placenta. Copyright © 2016. Published by Elsevier B.V.

  14. An unbiased approach to identifying tau kinases that phosphorylate tau at sites associated with Alzheimer disease.

    PubMed

    Cavallini, Annalisa; Brewerton, Suzanne; Bell, Amanda; Sargent, Samantha; Glover, Sarah; Hardy, Clare; Moore, Roger; Calley, John; Ramachandran, Devaki; Poidinger, Michael; Karran, Eric; Davies, Peter; Hutton, Michael; Szekeres, Philip; Bose, Suchira

    2013-08-09

    Neurofibrillary tangles, one of the hallmarks of Alzheimer disease (AD), are composed of paired helical filaments of abnormally hyperphosphorylated tau. The accumulation of these proteinaceous aggregates in AD correlates with synaptic loss and severity of dementia. Identifying the kinases involved in the pathological phosphorylation of tau may identify novel targets for AD. We used an unbiased approach to study the effect of 352 human kinases on their ability to phosphorylate tau at epitopes associated with AD. The kinases were overexpressed together with the longest form of human tau in human neuroblastoma cells. Levels of total and phosphorylated tau (epitopes Ser(P)-202, Thr(P)-231, Ser(P)-235, and Ser(P)-396/404) were measured in cell lysates using AlphaScreen assays. GSK3α, GSK3β, and MAPK13 were found to be the most active tau kinases, phosphorylating tau at all four epitopes. We further dissected the effects of GSK3α and GSK3β using pharmacological and genetic tools in hTau primary cortical neurons. Pathway analysis of the kinases identified in the screen suggested mechanisms for regulation of total tau levels and tau phosphorylation; for example, kinases that affect total tau levels do so by inhibition or activation of translation. A network fishing approach with the kinase hits identified other key molecules putatively involved in tau phosphorylation pathways, including the G-protein signaling through the Ras family of GTPases (MAPK family) pathway. The findings identify novel tau kinases and novel pathways that may be relevant for AD and other tauopathies.

  15. Proteopathic tau seeding predicts tauopathy in vivo.

    PubMed

    Holmes, Brandon B; Furman, Jennifer L; Mahan, Thomas E; Yamasaki, Tritia R; Mirbaha, Hilda; Eades, William C; Belaygorod, Larisa; Cairns, Nigel J; Holtzman, David M; Diamond, Marc I

    2014-10-14

    Transcellular propagation of protein aggregates, or proteopathic seeds, may drive the progression of neurodegenerative diseases in a prion-like manner. In tauopathies such as Alzheimer's disease, this model predicts that tau seeds propagate pathology through the brain via cell-cell transfer in neural networks. The critical role of tau seeding activity is untested, however. It is unknown whether seeding anticipates and correlates with subsequent development of pathology as predicted for a causal agent. One major limitation has been the lack of a robust assay to measure proteopathic seeding activity in biological specimens. We engineered an ultrasensitive, specific, and facile FRET-based flow cytometry biosensor assay based on expression of tau or synuclein fusions to CFP and YFP, and confirmed its sensitivity and specificity to tau (∼ 300 fM) and synuclein (∼ 300 pM) fibrils. This assay readily discriminates Alzheimer's disease vs. Huntington's disease and aged control brains. We then carried out a detailed time-course study in P301S tauopathy mice, comparing seeding activity versus histological markers of tau pathology, including MC1, AT8, PG5, and Thioflavin S. We detected robust seeding activity at 1.5 mo, >1 mo before the earliest histopathological stain. Proteopathic tau seeding is thus an early and robust marker of tauopathy, suggesting a proximal role for tau seeds in neurodegeneration.

  16. Proteopathic tau seeding predicts tauopathy in vivo

    PubMed Central

    Holmes, Brandon B.; Furman, Jennifer L.; Mahan, Thomas E.; Yamasaki, Tritia R.; Mirbaha, Hilda; Eades, William C.; Belaygorod, Larisa; Cairns, Nigel J.; Holtzman, David M.; Diamond, Marc I.

    2014-01-01

    Transcellular propagation of protein aggregates, or proteopathic seeds, may drive the progression of neurodegenerative diseases in a prion-like manner. In tauopathies such as Alzheimer’s disease, this model predicts that tau seeds propagate pathology through the brain via cell–cell transfer in neural networks. The critical role of tau seeding activity is untested, however. It is unknown whether seeding anticipates and correlates with subsequent development of pathology as predicted for a causal agent. One major limitation has been the lack of a robust assay to measure proteopathic seeding activity in biological specimens. We engineered an ultrasensitive, specific, and facile FRET-based flow cytometry biosensor assay based on expression of tau or synuclein fusions to CFP and YFP, and confirmed its sensitivity and specificity to tau (∼300 fM) and synuclein (∼300 pM) fibrils. This assay readily discriminates Alzheimer’s disease vs. Huntington's disease and aged control brains. We then carried out a detailed time-course study in P301S tauopathy mice, comparing seeding activity versus histological markers of tau pathology, including MC1, AT8, PG5, and Thioflavin S. We detected robust seeding activity at 1.5 mo, >1 mo before the earliest histopathological stain. Proteopathic tau seeding is thus an early and robust marker of tauopathy, suggesting a proximal role for tau seeds in neurodegeneration. PMID:25261551

  17. Propagation of Tau Aggregates and Neurodegeneration.

    PubMed

    Goedert, Michel; Eisenberg, David S; Crowther, R Anthony

    2017-07-25

    A pathway from the natively unfolded microtubule-associated protein Tau to a highly structured amyloid fibril underlies human Tauopathies. This ordered assembly causes disease and represents the gain of toxic function. In recent years, evidence has accumulated to suggest that Tau inclusions form first in a small number of brain cells, from where they propagate to other regions, resulting in neurodegeneration and disease. Propagation of pathology is often called prion-like, which refers to the capacity of an assembled protein to induce the same abnormal conformation in a protein of the same kind, initiating a self-amplifying cascade. In addition, prion-like encompasses the release of protein aggregates from brain cells and their uptake by neighboring cells. In mice, the intracerebral injection of Tau inclusions induces the ordered assembly of monomeric Tau, followed by its spreading to distant brain regions. Conformational differences between Tau aggregates from transgenic mouse brain and in vitro assembled recombinant protein account for the greater seeding potency of brain aggregates. Short fibrils constitute the major species of seed-competent Tau in the brains of transgenic mice. The existence of multiple human Tauopathies with distinct fibril morphologies has led to the suggestion that different molecular conformers (or strains) of aggregated Tau exist.

  18. Tau pathology induces intraneuronal cholesterol accumulation.

    PubMed

    Glöckner, Frauke; Ohm, Thomas G

    2014-09-01

    Epidemiologic and experimental data suggest the involvement of cholesterol metabolism in the development and progression of Alzheimer disease and Niemann-Pick type C disease, but not of frontotemporal dementias. In these 3 neurodegenerative diseases, however, protein tau hyperphosphorylation and aggregation into neurofibrillary tangles are observed. To elucidate the relationship between cholesterol and tau, we compared sterol levels of neurons burdened with neurofibrillary tangles with those of their unaffected neighbors using semiquantitative filipin fluorescence microscopy in mice expressing P301L mutant human tau (a well-described model of FTDP-17) and in P301L transgenic mice lacking apolipoprotein E (the major cholesterol transporter in the brain). Cellular unesterified cholesterol was higher in neurons affected by tau pathology irrespective of apolipoprotein E deficiency. This argues for an impact of tau pathology on cellular cholesterol homeostasis. We suggest that there is a bidirectional mode of action: Disturbances in cellular cholesterol metabolism may promote tau pathology, but tau pathology may also alter neuronal cholesterol homeostasis; once it is established, a vicious cycle may promote neurofibrillary tangle formation.

  19. A Search for B+ to tau+ nu

    SciTech Connect

    Aubert, B.

    2007-06-26

    The authors present a search for the decay B{sup +} {yields} {tau}{sup +}{nu} using 383 x 10{sup 6} B{bar B} pairs collected at the {Upsilon}(4S) resonance with the BABAR detector at the SLAC PEP-II B-Factory. A sample of events with one reconstructed semileptonic B decay (B{sup -} {yields} D{sup 0}{ell}{sup -}{bar {nu}}{sub {ell}}X) is selected, and in the recoil a search for B{sup +} {yields} {tau}{sup +}{nu} is performed. The {tau} is identified in the following channels: {tau}{sup +} {yields} e{sup +}{nu}{bar {nu}}, {tau}{sup +} {yields} {mu}{sup +}{nu}{bar {nu}}, {tau}{sup +} {yields} {pi}{sup +} {bar {nu}} and {tau}{sup +} {yields} {pi}{sup +}{pi}{sup 0}{bar {nu}}. They measure a branching fraction of {Beta}(B{sup +} {yields} {tau}{sup +}{nu}) = (0.9 {+-} 0.6(stat.) {+-} 0.1(syst.)) x 10{sup -4}. In the absence of a significant signal, we calculate an upper limit at the 90% confidence level of {Beta}(B{sup +} {yields} {tau}{sup +}{nu}) < 1.7 x 10{sup -4}. They calculate the product of the B meson decay constant f{sub B} and |V{sub ub}| to be f{sub B} {center_dot} |V{sub ub}| = (7.2{sub -2.8}{sup +2.0}(stat.) {+-} 0.2(syst.)) x 10{sup -4} GeV.

  20. Intracerebral injection of preformed synthetic tau fibrils initiates widespread tauopathy and neuronal loss in the brains of tau transgenic mice.

    PubMed

    Peeraer, Eve; Bottelbergs, Astrid; Van Kolen, Kristof; Stancu, Ilie-Cosmin; Vasconcelos, Bruno; Mahieu, Michel; Duytschaever, Hilde; Ver Donck, Luc; Torremans, An; Sluydts, Ellen; Van Acker, Nathalie; Kemp, John A; Mercken, Marc; Brunden, Kurt R; Trojanowski, John Q; Dewachter, Ilse; Lee, Virginia M Y; Moechars, Diederik

    2015-01-01

    Neurofibrillary tangles composed of hyperphosphorylated fibrillized tau are found in numerous tauopathies including Alzheimer's disease. Increasing evidence suggests that tau pathology can be transmitted from cell-to-cell; however the mechanisms involved in the initiation of tau fibrillization and spreading of disease linked to progression of tau pathology are poorly understood. We show here that intracerebral injections of preformed synthetic tau fibrils into the hippocampus or frontal cortex of young tau transgenic mice expressing mutant human P301L tau induces tau hyperphosphorylation and aggregation around the site of injection, as well as a time-dependent propagation of tau pathology to interconnected brain areas distant from the injection site. Furthermore, we show that the tau pathology as a consequence of injection of tau preformed fibrils into the hippocampus induces selective loss of CA1 neurons. Together, our data confirm previous studies on the seeded induction and the spreading of tau pathology in a different tau transgenic mouse model and reveals neuronal loss associated with seeded tau pathology in tau transgenic mouse brain. These results further validate the utility of the tau seeding model in studying disease transmission, and provide a more complete in vivo tauopathy model with associated neurodegeneration which can be used to investigate the mechanisms involved in tau aggregation and spreading, as well as aid in the search for disease modifying treatments for Alzheimer's disease and related tauopathies. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Intracerebral injection of preformed synthetic tau fibrils initiates widespread tauopathy and neuronal loss in the brains of tau transgenic mice

    PubMed Central

    Peeraer, Eve; Bottelbergs, Astrid; Van Kolen, Kristof; Stancu, Ilie-Cosmin; Vasconcelos, Bruno; Mahieu, Michel; Duytschaever, Hilde; Ver Donck, Luc; Torremans, An; Sluydts, Ellen; Van Acker, Nathalie; Kemp, John A.; Mercken, Marc; Brunden, Kurt R.; Trojanowski, John Q.; Dewachter, Ilse; Lee, Virginia M.Y.; Moechars, Diederik

    2015-01-01

    Neurofibrillary tangles composed of hyperphosphorylated fibrillized tau are found in numerous tauopathies including Alzheimer's disease. Increasing evidence suggests that tau pathology can be transmitted from cell-to-cell; however the mechanisms involved in the initiation of tau fibrillization and spreading of disease linked to progression of tau pathology are poorly understood. We show here that intracerebral injections of preformed synthetic tau fibrils into the hippocampus or frontal cortex of young tau transgenic mice expressing mutant human P301L tau induces tau hyperphosphorylation and aggregation around the site of injection, as well as a time-dependent propagation of tau pathology to interconnected brain areas distant from the injection site. Furthermore, we show that the tau pathology as a consequence of injection of tau preformed fibrils into the hippocampus induces selective loss of CA1 neurons. Together, our data confirm previous studies on the seeded induction and the spreading of tau pathology in a different tau transgenic mouse model and reveals neuronal loss associated with seeded tau pathology in tau transgenic mouse brain. These results further validate the utility of the tau seeding model in studying disease transmission, and provide a more complete in vivo tauopathy model with associated neurodegeneration which can be used to investigate the mechanisms involved in tau aggregation and spreading, as well as aid in the search for disease modifying treatments for Alzheimer's disease and related tauopathies. PMID:25220759

  2. Characteristics of yogurt-like products prepared from the combination of skim milk and soymilk containing saccharified-rice solution.

    PubMed

    Park, Dong June; Oh, Sejong; Ku, Kyung Hyung; Mok, Chulkyoon; Kim, Sae Hun; Imm, Jee-Young

    2005-02-01

    Yogurt-like products were prepared from a combination of skim milk and soymilk (100:0, 75:25, 50:50, 25:75, and 0:100) containing saccharified-rice solution by lactic fermentation of four different cultures. The ratio of skim milk and soy milk had no significant effect on titratable acidity, while the type and nature of culture used for fermentation affected the titratable acidity. Lower syneresis was observed in soy-based yogurt, and both the hardness and springiness of curd increased as the proportion of soymilk in the substrate increased. Skim milk-based yogurt had higher resistance to shear force with higher yield stress. The sensory quality of yogurt produced from mixed culture had higher preference compared with that produced from a single culture (Streptococcus thermophilus). There was no significant difference in texture and overall acceptability among yogurts produced from mixed substrates and skim milk-based yogurt.

  3. NMR observation of Tau in Xenopus oocytes

    NASA Astrophysics Data System (ADS)

    Bodart, Jean-François; Wieruszeski, Jean-Michel; Amniai, Laziza; Leroy, Arnaud; Landrieu, Isabelle; Rousseau-Lescuyer, Arlette; Vilain, Jean-Pierre; Lippens, Guy

    2008-06-01

    The observation by NMR spectroscopy of microinjected 15N-labelled proteins into Xenopus laevis oocytes might open the way to link structural and cellular biology. We show here that embedding the oocytes into a 20% Ficoll solution maintains their structural integrity over extended periods of time, allowing for the detection of nearly physiological protein concentrations. We use these novel conditions to study the neuronal Tau protein inside the oocytes. Spectral reproducibility and careful comparison of the spectra of Tau before and after cell homogenization is presented. When injecting Tau protein into immature oocytes, we show that both its microtubule association and different phosphorylation events can be detected.

  4. Tensor mesons produced in tau lepton decays

    SciTech Connect

    Lopez Castro, G.; Munoz, J. H.

    2011-05-01

    Light tensor mesons (T=a{sub 2}, f{sub 2} and K{sub 2}*) can be produced in decays of {tau} leptons. In this paper we compute the branching ratios of {tau}{yields}T{pi}{nu} decays by assuming the dominance of intermediate virtual states to model the form factors involved in the relevant hadronic matrix elements. The exclusive f{sub 2}(1270){pi}{sup -} decay mode turns out to have the largest branching ratio, of O(10{sup -4}). Our results indicate that the contribution of tensor meson intermediate states to the three-pseudoscalar channels of {tau} decays are rather small.

  5. Tau pathophysiology in neurodegeneration: a tangled issue.

    PubMed

    Spires-Jones, Tara L; Stoothoff, William H; de Calignon, Alix; Jones, Phillip B; Hyman, Bradley T

    2009-03-01

    Neurodegenerative tauopathies are marked by their common pathologic feature of aggregates formed of hyperphosphorylated tau protein, which are associated with synapse and neuronal loss. Changes in tau conformation result in both loss of normal function and gain of fibrillogenicity that leads to aggregation. Here, we discuss the pathophysiology of tau and emerging evidence of how changes in this protein might ultimately lead to neuronal death. In particular, based on recent evidence, we propose that a non-apoptotic caspase-associated form of death is occurring in tauopathy.

  6. Production of BaBar Skimmed Analysis Datasets Using the Grid

    SciTech Connect

    Brew, C.A.J.; Wilson, F.F.; Castelli, G.; Adye, T.; Roethel, W.; Luppi, E.; Andreotti, D.; Smith, D.; Khan, A.; Barrett, M.; Barlow, R.; Bailey, D.; /Manchester U.

    2011-11-10

    The BABAR Collaboration, based at Stanford Linear Accelerator Center (SLAC), Stanford, US, has been performing physics reconstruction, simulation studies and data analysis for 8 years using a number of compute farms around the world. Recent developments in Grid technologies could provide a way to manage the distributed resources in a single coherent structure. We describe enhancements to the BABAR experiment's distributed skimmed dataset production system to make use of European Grid resources and present the results with regard to BABAR's latest cycle of skimmed dataset production. We compare the benefits of a local and Grid-based systems, the ease with which the system is managed and the challenges of integrating the Grid with legacy software. We compare job success rates and manageability issues between Grid and non-Grid production.

  7. The effect of addition of skimmed milk on the characteristics of Myzithra cheeses.

    PubMed

    Kaminarides, S; Ilias-Dimopoulos, E; Zoidou, E; Moatsou, G

    2015-08-01

    Myzithra cheese is a traditional Greek whey cheese. Three types of Myzithra cheese were produced from A: 100% whey; B: 90% whey+10% ovine milk and C: 90% whey+10% skimmed ovine milk and were evaluated. The addition of skimmed milk to whey resulted in a new dietary product, containing 9.24% fat, with good quality, a harder texture and higher levels of ash, Ca, Mg and K than those of experimental cheeses A and B. Electrophoretic patterns and HPLC chromatograms of the proteins of Myzithra cheeses revealed the presence or not of αs-CN to the whey cheeses. In addition, SDS-electrophoresis of proteins under special preparation of samples permitted for first time the separation of whey-cheese protein (WP) components that had been denatured during cooking of the whey.

  8. Acetylation of Tau Inhibits Its Degradation and Contributes to Tauopathy

    PubMed Central

    Min, Sang-Won; Cho, Seo-Hyun; Zhou, Yungui; Schroeder, Sebastian; Haroutunian, Vahram; Seeley, William W.; Huang, Eric J.; Shen, Yong; Masliah, Eliezer; Mukherjee, Chandrani; Meyers, David; Cole, Philip A.; Ott, Melanie; Gan, Li

    2011-01-01

    Summary Neurodegenerative tauopathies characterized by hyperphosphorylated tau include frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) and Alzheimer's disease (AD). Reducing tau levels improves cognitive function in mouse models of AD and FTDP-17, but the mechanisms regulating the turnover of pathogenic tau are unknown. We found that tau is acetylated and that tau acetylation prevents degradation of phosphorylated tau (p-tau). Using two antibodies specific for acetylated tau, we showed that tau acetylation is elevated in patients at early and moderate Braak stages of tauopathy. Histone acetyltransferase p300 was involved in tau acetylation and the class III protein deacetylase SIRT1 in deacetylation. Deleting SIRT1 enhanced levels of acetylated-tau and pathogenic forms of p-tau in vivo, likely by blocking proteasome-mediated degradation. Inhibiting p300 with a small molecule promoted tau deacetylation and eliminated p-tau associated with tauopathy. Modulating tau acetylation could be a new therapeutic strategy to reduce tau-mediated neurodegeneration. PMID:20869593

  9. The role of the VQIVYK peptide in tau protein phosphorylation.

    PubMed

    Perez, Mar; Santa-María, Ismael; Tortosa, Elena; Cuadros, Raquel; Del Valle, Mercedes; Hernández, Felix; Moreno, Francisco J; Avila, Jesús

    2007-11-01

    Although it remains unclear whether they are related to one another, tau aggregation and phosphorylation are the main pathological hallmarks of the neuronal disorders known as tauopathies. The capacity to aggregate is impaired in a variant of the tau 3R isoform that lacks residues 306-311 (nomenclature for the largest CNS tau isoform) and hence, we have taken advantage of this feature to study how phosphorylation and aggregation may be related as well as the role of this six amino acid peptide (VQIVYK). Through these analyses, we found that the phosphorylation of the tau variant was higher than that of the complete tau protein and that not only the deletion of these residues, but also the interaction of these residues, in tau 3R, with thioflavin-S augmented tau phosphorylation by glycogen synthase kinase 3. In addition, the binding of the peptide containing the residues 306-311 to the whole tau protein provoked an increase in tau phosphorylation. This observation could be physiologically relevant as may suggest that tau-tau interactions, through those residues, facilitate tau phosphorylation. In summary, our data indicate that deletion of residues VQIVYK, in tau protein produces an increase in tau phosphorylation, without tau aggregation, because the VQIVYK peptide, that favors aggregation, is missing. On the other hand, when the whole tau protein interacts with thioflavin-S or the peptide VQIVYK, an increase in both aggregation and phosphorylation occurs.

  10. Counter-current carbon dioxide extraction of fat from soy skim

    USDA-ARS?s Scientific Manuscript database

    This research aims to investigate the use of counter-current carbon dioxide extraction method as a means to reduce residual fat in soy skim after the enzyme-assisted aqueous extraction of soybeans. Extractions with liquid CO2 at 25°C and 10.34 MPa and supercritical CO2 at 50°C and 25.16 MPa are comp...

  11. Performance assessment of membrane distillation for skim milk and whey processing.

    PubMed

    Hausmann, Angela; Sanciolo, Peter; Vasiljevic, Todor; Kulozik, Ulrich; Duke, Mikel

    2014-01-01

    Membrane distillation is an emerging membrane process based on evaporation of a volatile solvent. One of its often stated advantages is the low flux sensitivity toward concentration of the processed fluid, in contrast to reverse osmosis. In the present paper, we looked at 2 high-solids applications of the dairy industry: skim milk and whey. Performance was assessed under various hydrodynamic conditions to investigate the feasibility of fouling mitigation by changing the operating parameters and to compare performance to widespread membrane filtration processes. Whereas filtration processes are hydraulic pressure driven, membrane distillation uses vapor pressure from heat to drive separation and, therefore, operating parameters have a different bearing on the process. Experimental and calculated results identified factors influencing heat and mass transfer under various operating conditions using polytetrafluoroethylene flat-sheet membranes. Linear velocity was found to influence performance during skim milk processing but not during whey processing. Lower feed and higher permeate temperature was found to reduce fouling in the processing of both dairy solutions. Concentration of skim milk and whey by membrane distillation has potential, as it showed high rejection (>99%) of all dairy components and can operate using low electrical energy and pressures (<10 kPa). At higher cross-flow velocities (around 0.141 m/s), fluxes were comparable to those found with reverse osmosis, achieving a sustainable flux of approximately 12 kg/h·m(2) for skim milk of 20% dry matter concentration and approximately 20 kg/h·m(2) after 18 h of operation with whey at 20% dry matter concentration.

  12. Cholesterol-loaded cyclodextrin improves ram sperm cryoresistance in skim milk-extender.

    PubMed

    Salmon, Vianney M; Castonguay, François; Demers-Caron, Vincent; Leclerc, Pierre; Bailey, Janice L

    2017-02-01

    Cholesterol-loaded cyclodextrin (CLC) is known to improve ram sperm cryosurvival. This study expands on previous research to: (1) determine the mechanism by which CLC improves ram sperm cryosurvival and (2) compare the efficiency of a novel, skim milk-based extender containing CLC to a traditional egg yolk-based extender. Hypothesis #1 was that CLC enhances membrane cholesterol content to increase the resistance of ram sperm to cold and osmotic stress, thereby improving cryosurvival. We first assessed the ability of fresh sperm treated with CLC to withstand cold shock. Second, fresh sperm were treated with CLC to evaluate their tolerance to osmotic stress. Third, to confirm that cholesterol is incorporated into the sperm using CLC, we quantified sperm cholesterol. To test Hypothesis #2 that CLC is most effective in a medium without competing cholesterol, we compared sperm cryosurvival and fertility in skim milk-based extender containing CLC versus in a traditional egg yolk-based freezing extender without CLC. Our data confirmed that CLC treatment improves ram sperm cold shock and osmotic stress resistance, and augments sperm cholesterol content. Semen in skim milk-based extender containing CLC prior to freezing, had more motile sperm with intact acrosomes after thawing compared to semen in egg yolk-based extender. In contrast, sperm plasma membrane integrity and in vivo fertility of the semen cryopreserved in the skim milk-based extender with CLC did not differ from semen that was cryopreserved in egg yolk-based extender. Further research is warranted to combine CLC with other cryoprotection strategies or to modify the insemination protocol. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Anaerobic co-digestion of sewage sludge and primary clarifier skimmings for increased biogas production.

    PubMed

    Alanya, S; Yilmazel, Y D; Park, C; Willis, J L; Keaney, J; Kohl, P M; Hunt, J A; Duran, M

    2013-01-01

    The objective of the study was to identify the impact of co-digesting clarifier skimmings on the overall methane generation from the treatment plant and additional energy value of the increased methane production. Biogas production from co-digesting clarifier skimmings and sewage sludge in pilot-scale fed-batch mesophilic anaerobic digesters has been evaluated. The digester was fed with increasing quantities of clarifier skimmings loads: 1.5, 2.6, 3.5 and 7.0 g COD equivalent/(L·d) (COD: chemical oxygen demand). Average volatile solids reduction of 65% was achieved in the scum-fed digester, compared with 51% in the control digester. Average 69% COD removal was achieved at highest scum loading (7 g COD eq/(L·d)) with approximate methane yield of 250 L CH(4)/kg COD fed (4 ft(3)/lb COD fed). The results show that scum as co-substrate in anaerobic digestion systems improves biogas yields while a 29% increase in specific CH(4) yield could be achieved when scum load is 7 g COD eq/(L·d). Based on the pilot-scale study results and full-scale data from South East Water Pollution Control Plant and Northeast Water Pollution Control Plant the expected annual energy recovery would be approximately 1.7 billion BTUs or nearly 0.5 million kWh.

  14. Inactivation of Enterobacter aerogenes in reconstituted skim milk by high- and low-frequency ultrasound.

    PubMed

    Gao, Shengpu; Hemar, Yacine; Lewis, Gillian D; Ashokkumar, Muthupandian

    2014-11-01

    The inactivation of Enterobacter aerogenes in skim milk using low-frequency (20kHz) and high-frequency (850kHz) ultrasonication was investigated. It was found that low-frequency acoustic cavitation resulted in lethal damage to E. aerogenes. The bacteria were more sensitive to ultrasound in water than in reconstituted skim milk having different protein concentrations. However, high-frequency ultrasound was not able to inactivate E. aerogenes in milk even when powers as high as 50W for 60min were used. This study also showed that high-frequency ultrasonication had no influence on the viscosity and particle size of skim milk, whereas low-frequency ultrasonication resulted in the decrease in viscosity and particle size of milk. The decrease in particle size is believed to be due to the breakup of the fat globules, and possibly to the cleavage of the κ-casein present at the surface of the casein micelles. Whey proteins were also found to be slightly affected by low-frequency ultrasound, with the amounts of α-lactalbumin and β-lactoglobulin slightly decreasing.

  15. Chemical stability of astaxanthin nanodispersions in orange juice and skimmed milk as model food systems.

    PubMed

    Anarjan, Navideh; Tan, Chin Ping

    2013-08-15

    Solubilising astaxanthin in nanodispersion systems is a promising approach to incorporate astaxanthin into water-based food formulations. In this research, the chemical stabilities of astaxanthin nanodispersions diluted in orange juice and skimmed milk as model food systems and in deionised water as a control were evaluated. The nanodispersions displayed significantly (p<0.05) better stability in food systems compared to the control. The effects of stabilisers and dilution factor were also studied. In skimmed milk and deionised water, the type of stabiliser had a significant effect (p<0.05) on astaxanthin degradation during storage. In vitro cellular uptake of astaxanthin from diluted astaxanthin nanodispersions in selected food systems was also evaluated. The cellular uptake of astaxanthin nanodispersions in skimmed milk was significantly higher (p<0.05) than that of astaxanthin nanodispersions in orange juice and deionised water. High in vitro cellular uptake of astaxanthin from the prepared astaxanthin nanodispersions can be achieved via incorporation into protein-based foods such as milk. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Concentration of field and skim latex by microfiltration - membrane fouling and biochemical methane potential of serum.

    PubMed

    Thongmak, Narumol; Sridang, Porntip; Puetpaiboon, Udomphon; Grasmick, Alain

    2015-01-01

    Cross-flow microfiltration was used to concentrate field and skim latex suspensions and recover the smallest compounds (proteins, sugars, etc.) in permeate (serum solutions). The experiments were performed in a lab-scale microfiltration unit equipped with ceramic membranes. In continuous mode, the operations were performed at constant trans-membrane pressure (0.5 bars), constant cross-flow velocity (3 m/s) and constant temperature (28 ± 2°C). In retentate, the volumetric concentration factor was only close to 2 (about 54% of total solid content, TSC) when concentrating the field latex suspensions, and it reached 10 (close to 40% TSC) when concentrating skim latex suspensions. The quality of retentate suspensions let envisage a significant potential of industrial valorization. The membrane fouling rates appeared as an increasing function of dry rubber content suspension, and the main fouling origin (94%) was linked to a reversible accumulation of suspended compounds on the membrane surface. Permeate appeared as a clear yellow solution containing the smallest soluble organic fractions that show a high degree of biodegradability when using biochemical methane potential tests. The chemical oxygen demand (COD) removal was then higher than 92% and the methane production yield was close to 0.29 NLCH4/gCODremoved. The association of a membrane separation step and anaerobic digestion appeared, then, as a relevant solution to recover rubber content from skim latex suspensions and energy from the anaerobic digestion of serum.

  17. Geneious! Simplified genome skimming methods for phylogenetic systematic studies: A case study in Oreocarya (Boraginaceae)1

    PubMed Central

    Ripma, Lee A.; Simpson, Michael G.; Hasenstab-Lehman, Kristen

    2014-01-01

    • Premise of the study: As systematists grapple with how to best harness the power of next-generation sequencing (NGS), a deluge of review papers, methods, and analytical tools make choosing the right method difficult. Oreocarya (Boraginaceae), a genus of 63 species, is a good example of a group lacking both species-level resolution and genomic resources. The use of Geneious removes bioinformatic barriers and makes NGS genome skimming accessible to even the least tech-savvy systematists. • Methods: A combination of de novo and reference-guided assemblies was used to process 100-bp single-end Illumina HiSeq 2000 reads. A subset of 25 taxa was used to test the suitability of genome skimming for future systematic studies in recalcitrant lineages like Oreocarya. • Results: The nuclear ribosomal cistron, the plastome, and 12 mitochondrial genes were recovered from all 25 taxa. All data processing and phylogenomic analyses were performed in Geneious. We report possible future multiplexing levels and published low-copy nuclear genes represented within de novo contigs. • Discussion: Genome skimming represents a much-improved primary data collection over PCR+Sanger sequencing when chloroplast DNA (cpDNA), nuclear ribosomal DNA (nrDNA), and mitochondrial DNA (mtDNA) are the target sequences. This study details methods that plant systematists can employ to study their own taxa of interest. PMID:25506521

  18. Higgs mediated lepton flavor violating tau decays {tau}{yields}{mu}{gamma} and {tau}{yields}{mu}{gamma}{gamma} in effective theories

    SciTech Connect

    Aranda, J. I.; Tututi, E. S.; Toscano, J. J.

    2008-07-01

    The size of the branching ratios for the {tau}{yields}{mu}{gamma} and {tau}{yields}{mu}{gamma}{gamma} decays induced by a lepton flavor violating Higgs interaction H{tau}{mu} is studied in the framework of effective field theories. The best constraint on the H{tau}{mu} vertex, derived from the know measurement on the muon anomalous magnetic moment, is used to impose the upper bounds Br({tau}{yields}{mu}{gamma})<7.5x10{sup -10} and Br({tau}{yields}{mu}{gamma}{gamma})<2.3x10{sup -12}, which are more stringent than current experimental limits on this class of transitions.

  19. Accumulation of Filamentous Tau in the Cerebral Cortex of Human Tau R406W Transgenic Mice

    PubMed Central

    Ikeda, Masaki; Shoji†, Mikio; Kawarai, Toshitaka; Kawarabayashi, Takeshi; Matsubara, Etsuro; Murakami, Tetsuro; Sasaki, Atsushi; Tomidokoro, Yasushi; Ikarashi, Yasushi; Kuribara, Hisashi; Ishiguro, Koichi; Hasegawa, Masato; Yen, Shu-Hui; Chishti, M. Azhar; Harigaya, Yasuo; Abe, Koji; Okamoto, Koichi; St. George-Hyslop, Peter; Westaway, David

    2005-01-01

    Missense mutations of the tau gene cause autosomal dominant frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), an illness characterized by progressive personality changes, dementia, and parkinsonism. There is prominent frontotemporal lobe atrophy of the brain accompanied by abundant tau accumulation with neurofibrillary tangles and neuronal cell loss. Using a hamster prion protein gene expression vector, we generated several independent lines of transgenic (Tg) mice expressing the longest form of the human four-repeat tau with the R406W mutation associated with FTDP-17. The TgTauR406W 21807 line showed tau accumulation beginning in the hippocampus and amygdala at 6 months of age, which subsequently spread to the cortices and subcortical areas. The accumulated tau was phosphorylated, ubiquitinated, conformationally changed, argyrophilic, and sarcosyl-insoluble. Activation of GSK-3β and astrocytic induction of mouse tau were observed. Astrogliosis and microgliosis correlated with prominent tau accumulation. Electron microscopic examination revealed the presence of straight filaments. Behavioral tests showed motor disturbances and progressive acquired memory loss between 10 to 12 months of age. These findings suggested that TgTauR406W mice would be a useful model in the study of frontotemporal dementia and other tauopathies such as Alzheimer’s disease (AD). PMID:15681835

  20. Search for the rare decay B0-->tau+tau- at BABAR.

    PubMed

    Aubert, B; Barate, R; Boutigny, D; Couderc, F; Karyotakis, Y; Lees, J P; Poireau, V; Tisserand, V; Zghiche, A; Grauges, E; Palano, A; Pappagallo, M; Pompili, A; Chen, J C; Qi, N D; Rong, G; Wang, P; Zhu, Y S; Eigen, G; Ofte, I; Stugu, B; Abrams, G S; Battaglia, M; Breon, A B; Brown, D N; Button-Shafer, J; Cahn, R N; Charles, E; Day, C T; Gill, M S; Gritsan, A V; Groysman, Y; Jacobsen, R G; Kadel, R W; Kadyk, J; Kerth, L T; Kolomensky, Yu G; Kukartsev, G; Lynch, G; Mir, L M; Oddone, P J; Orimoto, T J; Pripstein, M; Roe, N A; Ronan, M T; Wenzel, W A; Barrett, M; Ford, K E; Harrison, T J; Hart, A J; Hawkes, C M; Morgan, S E; Watson, A T; Fritsch, M; Goetzen, K; Held, T; Koch, H; Lewandowski, B; Pelizaeus, M; Peters, K; Schroeder, T; Steinke, M; Boyd, J T; Burke, J P; Chevalier, N; Cottingham, W N; Cuhadar-Donszelmann, T; Fulsom, B G; Hearty, C; Knecht, N S; Mattison, T S; McKenna, J A; Khan, A; Kyberd, P; Saleem, M; Teodorescu, L; Blinov, A E; Blinov, V E; Bukin, A D; Druzhinin, V P; Golubev, V B; Kravchenko, E A; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Yushkov, A N; Best, D; Bondioli, M; Bruinsma, M; Chao, M; Curry, S; Eschrich, I; Kirkby, D; Lankford, A J; Lund, P; Mandelkern, M; Mommsen, R K; Roethel, W; Stoker, D P; Buchanan, C; Hartfiel, B L; Weinstein, A J R; Foulkes, S D; Gary, J W; Long, O; Shen, B C; Wang, K; Zhang, L; del Re, D; Hadavand, H K; Hill, E J; MacFarlane, D B; Paar, H P; Rahatlou, S; Sharma, V; Berryhill, J W; Campagnari, C; Cunha, A; Dahmes, B; Hong, T M; Mazur, M A; Richman, J D; Verkerke, W; Beck, T W; Eisner, A M; Flacco, C J; Heusch, C A; Kroseberg, J; Lockman, W S; Nesom, G; Schalk, T; Schumm, B A; Seiden, A; Spradlin, P; Williams, D C; Wilson, M G; Albert, J; Chen, E; Dubois-Felsmann, G P; Dvoretskii, A; Hitlin, D G; Narsky, I; Piatenko, T; Porter, F C; Ryd, A; Samuel, A; Andreassen, R; Mancinelli, G; Meadows, B T; Sokoloff, M D; Blanc, F; Bloom, P; Chen, S; Ford, W T; Hirschauer, J F; Kreisel, A; Nauenberg, U; Olivas, A; Rankin, P; Ruddick, W O; Smith, J G; Ulmer, K A; Wagner, S R; Zhang, J; Chen, A; Eckhart, E A; Harton, J L; Soffer, A; Toki, W H; Wilson, R J; Zeng, Q; Aleksan, R; Emery, S; Gaidot, A; Ganzhur, S F; Giraud, P-F; Graziani, G; Hamel de Monchenault, G; Kozanecki, W; Legendre, M; London, G W; Mayer, B; Vasseur, G; Yeche, Ch; Zito, M; Altenburg, D; Feltresi, E; Hauke, A; Spaan, B; Brandt, T; Brose, J; Dickopp, M; Klose, V; Lacker, H M; Nogowski, R; Otto, S; Petzold, A; Schubert, J; Schubert, K R; Schwierz, R; Sundermann, J E; Bernard, D; Bonneaud, G R; Grenier, P; Schrenk, S; Thiebaux, Ch; Vasileiadis, G; Verderi, M; Bard, D J; Clark, P J; Gradl, W; Muheim, F; Playfer, S; Xie, Y; Andreotti, M; Azzolini, V; Bettoni, D; Bozzi, C; Calabrese, R; Cibinetto, G; Luppi, E; Negrini, M; Piemontese, L; Anulli, F; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Finocchiaro, G; Patteri, P; Peruzzi, I M; Piccolo, M; Zallo, A; Buzzo, A; Capra, R; Contri, R; Lo Vetere, M; Macri, M; Monge, M R; Passaggio, S; Patrignani, C; Robutti, E; Santroni, A; Tosi, S; Brandenburg, G; Chaisanguanthum, K S; Morii, M; Won, E; Wu, J; Dubitzky, R S; Langenegger, U; Marks, J; Schenk, S; Uwer, U; Martinez-Vidal, F; Bhimji, W; Bowerman, D A; Dauncey, P D; Egede, U; Flack, R L; Gaillard, J R; Morton, G W; Nash, J A; Nikolich, M B; Taylor, G P; Vazquez, W P; Charles, M J; Mader, W F; Mallik, U; Mohapatra, A K; Cochran, J; Crawley, H B; Eyges, V; Meyer, W T; Prell, S; Rosenberg, E I; Rubin, A E; Yi, J; Biasini, M; Covarelli, R; Pacetti, S; Pioppi, M; Arnaud, N; Davier, M; Giroux, X; Grosdidier, G; Höcker, A; Le Diberder, F; Lepeltier, V; Lutz, A M; Oyanguren, A; Petersen, T C; Pierini, M; Plaszczynski, S; Rodier, S; Roudeau, P; Schune, M H; Stocchi, A; Wormser, G; Cheng, C H; Lange, D J; Simani, M C; Wright, D M; Bevan, A J; Chavez, C A; Forster, Ian J; Fry, J R; Gabathuler, E; Gamet, R; George, K A; Hutchcroft, D E; Parry, R J; Payne, D J; Schofield, K C; Touramanis, C; Cormack, C M; Di Lodovico, F; Menges, W; Sacco, R; Brown, C L; Cowan, G; Flaecher, H U; Green, M G; Hopkins, D A; Jackson, P S; McMahon, T R; Ricciardi, S; Salvatore, F; Brown, D; Davis, C L; Allison, J; Barlow, N R; Barlow, R J; Edgar, C L; Hodgkinson, M C; Kelly, M P; Lafferty, G D; Naisbit, M T; Williams, J C; Chen, C; Hulsbergen, W D; Jawahery, A; Kovalskyi, D; Lae, C K; Roberts, D A; Simi, G; Blaylock, G; Dallapiccola, C; Hertzbach, S S; Kofler, R; Koptchev, V B; Li, X; Moore, T B; Saremi, S; Staengle, H; Willocq, S; Cowan, R; Koeneke, K; Sciolla, G; Sekula, S J; Spitznagel, M; Taylor, F; Yamamoto, R K; Kim, H; Patel, P M; Robertson, S H; Lazzaro, A; Lombardo, V; Palombo, F; Bauer, J M; Cremaldi, L; Eschenburg, V; Godang, R; Kroeger, R; Reidy, J; Sanders, D A; Summers, D J; Zhao, H W; Brunet, S; Cote, D; Taras, P; Viaud, B; Nicholson, H; Baak, M; Bulten, H; Raven, G; Snoek, H L; Wilden, L; Cavallo, N; De Nardo, G; Fabozzi, F; Gatto, C; Lista, L; Monorchio, D; Paolucci, P; Piccolo, D; Sciacca, C; Jessop, C P; LoSecco, J M; Allmendinger, T; Benelli, G; Gan, K K; Honscheid, K; Hufnagel, D; Jackson, P D; Kagan, H; Kass, R; Pulliam, T; Rahimi, A M; Ter-Antonyan, R; Wong, Q K; Brau, J; Frey, R; Igonkina, O; Lu, M; Potter, C T; Sinev, N B; Strom, D; Strube, J; Torrence, E; Galeazzi, F; Margoni, M; Morandin, M; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Voci, C; Benayoun, M; Briand, H; Chauveau, J; David, P; de la Vaissiere, C; Del Buono, L; Hamon, O; John, M J J; Leruste, Ph; Malcles, J; Ocariz, J; Roos, L; Therin, G; Behera, P K; Gladney, L; Guo, Q H; Panetta, J; Angelini, C; Batignani, G; Bettarini, S; Bucci, F; Calderini, G; Carpinelli, M; Cenci, R; Forti, F; Giorgi, M A; Lusiani, A; Marchiori, G; Morganit, M; Neri, N; Paoloni, E; Rama, M; Rizzo, G; Walsh, J; Haire, M; Judd, D; Wagoner, D E; Biesiada, J; Danielson, N; Elmer, P; Lau, Y; Lu, C; Olsen, J; Smith, A J S; Telnov, A V; Bellini, F; Cavoto, G; D'Orazio, A; Di Marco, E; Faccini, R; Ferrarotto, F; Ferroni, F; Gaspero, M; Li Gioi, L; Mazzoni, M A; Morganti, S; Piredda, G; Polci, F; Safai Tehrani, F; Voena, C; Schröder, H; Wagner, G; Waldi, R; Adye, T; De Groot, N; Franek, B; Gopal, G P; Olaiya, E O; Wilson, F F; Purohit, M V; Weidemann, A W; Wilson, J R; Yumiceva, F X; Abe, T; Allen, M T; Aston, D; Bartoldus, R; Berger, N; Boyarski, A M; Buchmueller, O L; Claus, R; Coleman, J P; Convery, M R; Cristinziani, M; Dingfelder, J C; Dong, D; Dorfan, J; Dujmic, D; Dunwoodie, W; Fan, S; Field, R C; Glanzman, T; Gowdy, S J; Hadig, T; Halyo, V; Hast, C; Hryn'ova, T; Innes, W R; Kelsey, M H; Kim, P; Kocian, M L; Leith, D W G S; Libby, J; Luitz, S; Luth, V; Lynch, H L; Marsiske, H; Messner, R; Muller, D R; O'Grady, C P; Ozcan, V E; Perazzo, A; Perl, M; Ratcliff, B N; Roodman, A; Salnikov, A A; Schindler, R H; Schwiening, J; Snyder, A; Stelzer, J; Su, D; Sullivan, M K; Suzuki, K; Swain, S K; Thompson, J M; Va'vra, J; van Bakel, N; Weaver, M; Wisniewski, W J; Wittgen, M; Wright, D H; Yarritu, A K; Yi, K; Young, C C; Burchat, P R; Edwards, A J; Majewski, S A; Petersen, B A; Roat, C; Ahmed, M; Ahmed, S; Alam, M S; Bula, R; Ernst, J A; Saeed, M A; Wappler, F R; Zain, S B; Bugg, W; Krishnamurthy, M; Spanier, S M; Eckmann, R; Ritchie, J L; Satpathy, A; Schwitters, R F; Izen, J M; Kitayama, I; Lou, X C; Ye, S; Bianchi, F; Bona, M; Gallo, F; Gamba, D; Bomben, M; Bosisio, L; Cartaro, C; Cossutti, F; Della Ricca, G; Dittongo, S; Grancagnolo, S; Lanceri, L; Vitale, L; Panvini, R S; Banerjee, Sw; Bhuyan, B; Brown, C M; Fortin, D; Hamano, K; Kowalewski, R; Roney, J M; Sobie, R J; Back, J J; Harrison, P F; Latham, T E; Mohanty, G B; Band, H R; Chen, X; Cheng, B; Dasu, S; Datta, M; Eichenbaum, A M; Flood, K T; Graham, M; Hollar, J J; Johnson, J R; Kutter, P E; Li, H; Liu, R; Mellado, B; Mihalyi, A; Pan, Y; Prepost, R; Tan, P; von Wimmersperg-Toeller, J H; Wu, S L; Yu, Z; Neal, H; Schott, G

    2006-06-23

    We present the results of a search for the decay B0-->tau+tau- in a data sample of (232+/-3)x10(6) Upsilon(4S)-->BB decays using the BABAR detector. Certain extensions of the standard model predict measurable levels of this otherwise rare decay. We reconstruct fully one neutral B meson and seek evidence for the signal decay in the rest of the event. We find no evidence for signal events and obtain Beta(B0->tau+tau-)<4.1x10(-3) at the 90% confidence level.

  1. Searches for Lepton Flavor Violation in the Decays tau+- ---> e+- gamma and tau+- ---> mu+- gamma

    SciTech Connect

    Aubert, Bernard; Karyotakis, Y.; Lees, J.P.; Poireau, V.; Prencipe, E.; Prudent, X.; Tisserand, V.; Garra Tico, J.; Grauges, E.; Martinelli, M.; Palano, A.; Pappagallo, M.; Eigen, G.; Stugu, B.; Sun, L.; Battaglia, M.; Brown, David Nathan; Hooberman, B.; Kerth, L.T.; Kolomensky, Yu.G.; Lynch, G.; /more authors..

    2010-06-11

    Searches for lepton-flavor-violating decays of a {tau} lepton to a lighter mass lepton and a photon have been performed with the entire dataset of (963 {+-} 7) x 10{sup 6} {tau} decays collected by the BABAR detector near the {Upsilon}(4S), {Upsilon}(3S) and {Upsilon}(2S) resonances. The searches yield no evidence of signals and they set upper limits on the branching fractions of {Beta}({tau}{sup {+-}} {yields} e{sup {+-}}{gamma}) < 3.3 x 10{sup -8} and {Beta}({tau}{sup {+-}} {yields} {mu}{sup {+-}}{gamma}) < 4.4 x 10{sup -8} at 90% confidence level.

  2. Orbital motions and light curves of young binaries XZ Tau and VY Tau

    NASA Astrophysics Data System (ADS)

    Dodin, A. V.; Emelyanov, N. V.; Zharova, A. V.; Lamzin, S. A.; Malogolovets, E. V.; Roe, J. M.

    2016-01-01

    The results of our speckle interferometric observations of young binaries VY Tau and XZ Tau are presented. For the first time, we found a relative displacement of VY Tau components as well as a preliminary orbit for XZ Tau. It appeared that the orbit is appreciably non-circular and is inclined by i ≲ 47◦ from the plane of the sky. It means that the rotation axis of XZ Tau A and the axis of its jet are significantly non-perpendicular to the orbital plane. We found that the average brightness of XZ Tau had been increasing from the beginning of the last century up to the mid-thirties and then it decreased by Δ B > 2 mag. The maximal brightness has been reached significantly later on the time of periastron passage. The total brightness of XZ Tau's components varied in a non-regular way from 1970 to 1985 when eruptions of hot gas from XZ Tau A presumably had occurred. In the early nineties the variations became regular following which a chaotic variability had renewed. We also report that a flare activity of VY Tau has resumed after 40 yr pause, parameters of the previous and new flares are similar, and the flares are related with the A component.

  3. Survey of Volatiles in the Disks Around GV Tau N and AA Tau

    NASA Astrophysics Data System (ADS)

    Gibb, Erika

    2010-02-01

    We propose to use NIRSPEC to characterize the gas phase volatiles, particularly organic molecules, in circumstellar disks toward Tauri stars GV Tau N and AA Tau. These sources have recently been found to exhibit rich molecular absorption (GV Tau N; Gibb et al. 2007) and emission (AA Tau; Carr et al. 2008) spectra that sample distinct regions of the circumstellar disk. If we are to understand the distribution of materials in disks and place our solar system in context, these systems must be studied in detail. As such, we propose to perform a near-infrared survey of these two sources.

  4. Anti-tau antibody reduces insoluble tau and decreases brain atrophy

    PubMed Central

    Yanamandra, Kiran; Jiang, Hong; Mahan, Thomas E; Maloney, Susan E; Wozniak, David F; Diamond, Marc I; Holtzman, David M

    2015-01-01

    Objective We previously found a strong reduction in tau pathology and insoluble tau in P301S tau transgenic mice following intracerebroventricular infusion of the anti-tau antibody HJ8.5. We sought to determine the effects of HJ8.5 in the same model following peripheral administration. Methods The primary objective was to determine if HJ8.5 administered at a dose of 50 mg kg−1 week−1 by intraperitoneal (IP) injection to 6-month-old P301S mice for 3 months would influence phospho-tau (p-tau) accumulation, tau insolubility, and neurodegeneration. Results Treatment with HJ8.5 at 50 mg/kg showed a very strong decrease in detergent-insoluble tau. Importantly, HJ8.5 significantly reduced the loss of cortical and hippocampal tissue volumes compared to control treated mice. HJ8.5 treatment reduced hippocampal CA1 cellular layer staining with the p-tau antibody AT8 and thio-S-positive tau aggregates in piriform cortex and amygdala. Moreover, mice treated with HJ8.5 at 50 mg/kg showed a decrease in motor/sensorimotor deficits compared to vehicle-treated mice. Some effects of HJ8.5, including reduction in brain atrophy, and p-tau immunostaining were also seen with a dose of 10 mg kg−1 week−1. In BV2-microglial cells, we observed significantly higher uptake of P301S tau aggregates in the presence of HJ8.5. HJ8.5 treatment also resulted in a large dose-dependent increase of tau in the plasma. Interpretation Our results indicate that systemically administered anti-tau antibody HJ8.5 significantly decreases insoluble tau, decreases brain atrophy, and improves motor/sensorimotor function in a mouse model of tauopathy. These data further support the idea that anti-tau antibodies should be further assessed as a potential treatment for tauopathies. PMID:25815354

  5. Antibody Therapeutics Targeting Aβ and Tau.

    PubMed

    Gallardo, Gilbert; Holtzman, David M

    2017-10-03

    The astonishing findings that active and passive immunization against amyloid-β (Aβ) in mouse models of Alzheimer's disease (AD) dramatically decreased amyloid burden led to a rapid initiation of human clinical trials with much enthusiasm. However, methodological issues and adverse effects relating to these clinical trials arose, challenging the effectiveness and safety of these reagents. Efforts are now underway to develop safer immunotherapeutic approaches toward Aβ and the treatment of individuals at risk for AD before or in the earliest stages of cognitive decline with new hopes. Furthermore, several studies have shown tau as a potential immunotherapeutic target for the treatment of tauopathy-related diseases including frontotemporal lobar dementia (FTLD). Both active and passive immunization targeting tau in mouse models of tauopathy effectively decreased tau pathology while improving cognitive performance. These preclinical studies have highlighted tau as an alternative target with much anticipation of clinical trials to be undertaken. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  6. The audiovisual tau effect in infancy.

    PubMed

    Kawabe, Takahiro; Shirai, Nobu; Wada, Yuji; Miura, Kayo; Kanazawa, So; Yamaguchi, Masami K

    2010-03-03

    Perceived spatial intervals between successive flashes can be distorted by varying the temporal intervals between them (the "tau effect"). A previous study showed that a tau effect for visual flashes could be induced when they were accompanied by auditory beeps with varied temporal intervals (an audiovisual tau effect). We conducted two experiments to investigate whether the audiovisual tau effect occurs in infancy. Forty-eight infants aged 5-8 months took part in this study. In Experiment 1, infants were familiarized with audiovisual stimuli consisting of three pairs of two flashes and three beeps. The onsets of the first and third pairs of flashes were respectively matched to those of the first and third beeps. The onset of the second pair of flashes was separated from that of the second beep by 150 ms. Following the familiarization phase, infants were exposed to a test stimulus composed of two vertical arrays of three static flashes with different spatial intervals. We hypothesized that if the audiovisual tau effect occurred in infancy then infants would preferentially look at the flash array with spatial intervals that would be expected to be different from the perceived spatial intervals between flashes they were exposed to in the familiarization phase. The results of Experiment 1 supported this hypothesis. In Experiment 2, the first and third beeps were removed from the familiarization stimuli, resulting in the disappearance of the audiovisual tau effect. This indicates that the modulation of temporal intervals among flashes by beeps was essential for the audiovisual tau effect to occur (Experiment 2). These results suggest that the cross-modal processing that underlies the audiovisual tau effect occurs even in early infancy. In particular, the results indicate that audiovisual modulation of temporal intervals emerges by 5-8 months of age.

  7. Ironing out Tau's Role in Parkinsonism

    PubMed Central

    Stankowski, Jeannette N.; Dawson, Valina L.; Dawson, Ted M.

    2015-01-01

    Parkinson's disease affects more than five million people worldwide, yet no therapeutic has been identified that can slow or halt the progression of this debilitating disease. A new study in tau knockout mice suggests that tau deficiency causes impaired ferroportin-coupled iron export, by retention of the amyloid precursor protein, a neuronal ferroxidase partner, in the endoplasmic reticulum. This leads to parkinsonism through intracellular iron accumulation and degeneration of dopamine neurons (pages X-Y). PMID:22310680

  8. Summary of the Tau 2016 Workshop

    NASA Astrophysics Data System (ADS)

    Lusiani, Alberto

    2017-06-01

    The main topics discussed at the Tau 2016 Workshop are briefly summarized. A large number of reports were given on low-energy QCD studies, on the hadronic g - 2 contribution, and on neutrino Physics. Other reports were given on the τ lepton properties and related topics, on Lepton Flavour Violation and New Physics searches involving tau-lepton production or light New Physics particles.

  9. Deletion of endogenous Tau proteins is not detrimental in Drosophila

    PubMed Central

    Burnouf, Sylvie; Grönke, Sebastian; Augustin, Hrvoje; Dols, Jacqueline; Gorsky, Marianna Karina; Werner, Jennifer; Kerr, Fiona; Alic, Nazif; Martinez, Pedro; Partridge, Linda

    2016-01-01

    Human Tau (hTau) is a highly soluble and natively unfolded protein that binds to microtubules within neurons. Its dysfunction and aggregation into insoluble paired helical filaments is involved in the pathogenesis of Alzheimer’s disease (AD), constituting, together with accumulated β-amyloid (Aβ) peptides, a hallmark of the disease. Deciphering both the loss-of-function and toxic gain-of-function of hTau proteins is crucial to further understand the mechanisms leading to neurodegeneration in AD. As the fruit fly Drosophila melanogaster expresses Tau proteins (dTau) that are homologous to hTau, we aimed to better comprehend dTau functions by generating a specific tau knock-out (KO) fly line using homologous recombination. We observed that the specific removal of endogenous dTau proteins did not lead to overt, macroscopic phenotypes in flies. Indeed, survival, climbing ability and neuronal function were unchanged in tau KO flies. In addition, we did not find any overt positive or negative effect of dTau removal on human Aβ-induced toxicity. Altogether, our results indicate that the absence of dTau proteins has no major functional impact on flies, and suggests that our tau KO strain is a relevant model to further investigate the role of dTau proteins in vivo, thereby giving additional insights into hTau functions. PMID:26976084

  10. The winds from HL Tau

    PubMed Central

    Klaassen, P. D.; Mottram, J. C.; Maud, L. T.; Juhasz, A.

    2016-01-01

    Outflowing motions, whether a wind launched from the disc, a jet launched from the protostar, or the entrained molecular outflow, appear to be a ubiquitous feature of star formation. These outwards motions have a number of root causes, and how they manifest is intricately linked to their environment as well as the process of star formation itself. Using the Atacama Large Millimeter/submillimeter Array (ALMA) Science Verification data of HL Tau, we investigate the high-velocity molecular gas being removed from the system as a result of the star formation process. We aim to place these motions in context with the optically detected jet, and the disc. With these high-resolution (∼1 arcsec) ALMA observations of CO (J=1−0), we quantify the outwards motions of the molecular gas. We find evidence for a bipolar outwards flow, with an opening angle, as measured in the redshifted lobe, starting off at 90°, and narrowing to 60° further from the disc, likely because of magnetic collimation. Its outwards velocity, corrected for inclination angle is of the order of 2.4 km s−1. PMID:27559304

  11. Tau longitudinal polarization in B{yields}D{tau}{nu} and its role in the search for the charged Higgs boson

    SciTech Connect

    Tanaka, Minoru; Watanabe, Ryoutaro

    2010-08-01

    We study the longitudinal polarization of the tau lepton in B{yields}D{tau}{nu} decay. After discussing possible sensitivities of {tau} decay modes to the {tau} polarization, we examine the effect of charged Higgs boson on the {tau} polarization in B{yields}D{tau}{nu}. We find a relation between the decay rate and the {tau} polarization, and clarify the role of the {tau} polarization measurement in the search for the charged Higgs boson.

  12. WATER VAPOR IN THE PROTOPLANETARY DISK OF DG Tau

    SciTech Connect

    Podio, L.; Dougados, C.; Thi, W.-F.; Menard, F.; Pinte, C.; Codella, C.; Cabrit, S.; Nisini, B.; Sandell, G.; Williams, J. P.; Testi, L.; Woitke, P.

    2013-03-20

    Water is key in the evolution of protoplanetary disks and the formation of comets and icy/water planets. While high-excitation water lines originating in the hot inner disk have been detected in several T Tauri stars (TTSs), water vapor from the outer disk, where most water ice reservoirs are stored, was only reported in the nearby TTS TW Hya. We present spectrally resolved Herschel/HIFI observations of the young TTS DG Tau in the ortho- and para-water ground-state transitions at 557 and 1113 GHz. The lines show a narrow double-peaked profile, consistent with an origin in the outer disk, and are {approx}19-26 times brighter than in TW Hya. In contrast, CO and [C II] lines are dominated by emission from the envelope/outflow, which makes H{sub 2}O lines a unique tracer of the disk of DG Tau. Disk modeling with the thermo-chemical code ProDiMo indicates that the strong UV field, due to the young age and strong accretion of DG Tau, irradiates a disk upper layer at 10-90 AU from the star, heating it up to temperatures of 600 K and producing the observed bright water lines. The models suggest a disk mass of 0.015-0.1 M{sub Sun }, consistent with the estimated minimum mass of the solar nebula before planet formation, and a water reservoir of {approx}10{sup 2}-10{sup 3} Earth oceans in vapor and {approx}100 times larger in the form of ice. Hence, this detection supports the scenario of ocean delivery on terrestrial planets by the impact of icy bodies forming in the outer disk.

  13. Vaccination with Sarkosyl insoluble PHF-tau decrease neurofibrillary tangles formation in aged tau transgenic mouse model: a pilot study.

    PubMed

    Ando, Kunie; Kabova, Anna; Stygelbout, Virginie; Leroy, Karelle; Heraud, Céline; Frédérick, Christelle; Suain, Valérie; Yilmaz, Zehra; Authelet, Michèle; Dedecker, Robert; Potier, Marie-Claude; Duyckaerts, Charles; Brion, Jean-Pierre

    2014-01-01

    Active immunization using tau phospho-peptides in tauopathy mouse models has been observed to reduce tau pathology, especially when given prior to the onset of pathology. Since tau aggregates in these models and in human tauopathies are composed of full-length tau with many post-translational modifications, and are composed of several tau isoforms in many of them, pathological tau proteins bearing all these post-translational modifications might prove to be optimal tau conformers to use as immunogens, especially in models with advanced tau pathology. To this aim, we immunized aged wild-type and mutant tau mice with preparations containing human paired helical filaments (PHF) emulsified in Alum-adjuvant. This immunization protocol with fibrillar PHF-tau was well tolerated and did not induce an inflammatory reaction in the brain or adverse effect in these aged mice. Mice immunized with four repeated injections developed anti-PHF-tau antibodies with rising titers that labeled human neurofibrillary tangles in situ. Immunized mutant tau mice had a lower density of hippocampal Gallyas-positive neurons. Brain levels of Sarkosyl-insoluble tau were also reduced in immunized mice. These results indicate that an immunization protocol using fibrillar PHF-tau proteins is an efficient and tolerated approach to reduce tau pathology in an aged tauopathy animal model.

  14. The decay. tau. sup minus r arrow K sup minus K sup +. pi. sup minus. nu. sub. tau. and the. nu. sub. tau. mass

    SciTech Connect

    Gomez-Cadenas, J.J. ); Gonzalez-Garcia, M.C.; Pich, A. Instituto de Fisica Corpuscular, Consejo Superior de Investigaciones Cientificas, Universidad de Valencia, Burjasot )

    1990-11-01

    In this paper, we present a model based on the effective chiral Lagrangian to describe the decay {tau}{sup {minus}}{r arrow}{ital K}{sup {minus}}{ital K}{sup +}{pi}{sup {minus}}{nu}{sub {tau}}. Using our model we study the possible limits on the {nu}{sub {tau}} mass that can be achieved by a high-statistics, high-precision experiment taking data close to the {tau}-pair production threshold.

  15. Results of magnetic field measurements in young stars DO Tau, DR Tau, and DS Tau

    NASA Astrophysics Data System (ADS)

    Dodin, A. V.; Lamzin, S. A.; Chuntonov, G. A.

    2013-04-01

    The results of longitudinal magnetic field measurements B z in the hot accretion spot in three classical T Tauri stars (CTTS) are reported. In all three stars the magnetic field is detected at a level above 2 σ in the formation region of the narrow component of the He I 5876 Å emission line. In the case of DS Tau the longitudinal field B z in the hot spot was also measured from the narrow emission components of the Na I D lines, implying +0.8 ± 0.3 kG, which is equal to the B z field component measured from the He I 5876 Å line. Our results suggest that the 6-m telescope of the Special Astrophysical Observatory can be used to study magnetic fields in the hot spots of CTTS with magnitudes down to 13m, making it possible to double the number of stars of this type with measured B z values in the accretion zone.

  16. How it all started: tau and protein phosphatase 2A.

    PubMed

    Liu, Chang; Götz, Jürgen

    2013-01-01

    This review is dedicated to Inge Grundke-Iqbal who laid the foundations of the tau field, by isolating tau from the Alzheimer's disease (AD) brain, discovering that tau is hyperphosphorylated, and proving a critical role of protein phosphatase 2A (PP2A) and its endogenous inhibitor I2PP2A in this process. This memorial starts with a few personal notes, and then covers how subcellular fractionation helped in isolating tau. We review in detail the role of PP2A and its endogenous inhibitor in tau phosphorylation. We discuss the role that methylation and phosphorylation have in regulating PP2A activity. We add what we have contributed to understanding the role of tau and PP2A in AD using PP2A transgenic and knockout models, and conclude by addressing two underexplored areas in tau research: tau's non-canonical functions and the role distinct tau isoforms have in a physiological context.

  17. Passive Immunization with Phospho-Tau Antibodies Reduces Tau Pathology and Functional Deficits in Two Distinct Mouse Tauopathy Models

    PubMed Central

    Sankaranarayanan, Sethu; Barten, Donna M.; Vana, Laurel; Devidze, Nino; Yang, Ling; Cadelina, Gregory; Hoque, Nina; DeCarr, Lynn; Keenan, Stefanie; Lin, Alan; Cao, Yang; Snyder, Bradley; Zhang, Bin; Nitla, Magdalena; Hirschfeld, Gregg; Barrezueta, Nestor; Polson, Craig; Wes, Paul; Rangan, Vangipuram S.; Cacace, Angela; Albright, Charles F.; Meredith, Jere; Trojanowski, John Q.; Lee, Virginia M-Y.; Brunden, Kurt R.; Ahlijanian, Michael

    2015-01-01

    In Alzheimer’s disease (AD), an extensive accumulation of extracellular amyloid plaques and intraneuronal tau tangles, along with neuronal loss, is evident in distinct brain regions. Staging of tau pathology by postmortem analysis of AD subjects suggests a sequence of initiation and subsequent spread of neurofibrillary tau tangles along defined brain anatomical pathways. Further, the severity of cognitive deficits correlates with the degree and extent of tau pathology. In this study, we demonstrate that phospho-tau (p-tau) antibodies, PHF6 and PHF13, can prevent the induction of tau pathology in primary neuron cultures. The impact of passive immunotherapy on the formation and spread of tau pathology, as well as functional deficits, was subsequently evaluated with these antibodies in two distinct transgenic mouse tauopathy models. The rTg4510 transgenic mouse is characterized by inducible over-expression of P301L mutant tau, and exhibits robust age-dependent brain tau pathology. Systemic treatment with PHF6 and PHF13 from 3 to 6 months of age led to a significant decline in brain and CSF p-tau levels. In a second model, injection of preformed tau fibrils (PFFs) comprised of recombinant tau protein encompassing the microtubule-repeat domains into the cortex and hippocampus of young P301S mutant tau over-expressing mice (PS19) led to robust tau pathology on the ipsilateral side with evidence of spread to distant sites, including the contralateral hippocampus and bilateral entorhinal cortex 4 weeks post-injection. Systemic treatment with PHF13 led to a significant decline in the spread of tau pathology in this model. The reduction in tau species after p-tau antibody treatment was associated with an improvement in novel-object recognition memory test in both models. These studies provide evidence supporting the use of tau immunotherapy as a potential treatment option for AD and other tauopathies. PMID:25933020

  18. Passive immunization with phospho-tau antibodies reduces tau pathology and functional deficits in two distinct mouse tauopathy models.

    PubMed

    Sankaranarayanan, Sethu; Barten, Donna M; Vana, Laurel; Devidze, Nino; Yang, Ling; Cadelina, Gregory; Hoque, Nina; DeCarr, Lynn; Keenan, Stefanie; Lin, Alan; Cao, Yang; Snyder, Bradley; Zhang, Bin; Nitla, Magdalena; Hirschfeld, Gregg; Barrezueta, Nestor; Polson, Craig; Wes, Paul; Rangan, Vangipuram S; Cacace, Angela; Albright, Charles F; Meredith, Jere; Trojanowski, John Q; Lee, Virginia M-Y; Brunden, Kurt R; Ahlijanian, Michael

    2015-01-01

    In Alzheimer's disease (AD), an extensive accumulation of extracellular amyloid plaques and intraneuronal tau tangles, along with neuronal loss, is evident in distinct brain regions. Staging of tau pathology by postmortem analysis of AD subjects suggests a sequence of initiation and subsequent spread of neurofibrillary tau tangles along defined brain anatomical pathways. Further, the severity of cognitive deficits correlates with the degree and extent of tau pathology. In this study, we demonstrate that phospho-tau (p-tau) antibodies, PHF6 and PHF13, can prevent the induction of tau pathology in primary neuron cultures. The impact of passive immunotherapy on the formation and spread of tau pathology, as well as functional deficits, was subsequently evaluated with these antibodies in two distinct transgenic mouse tauopathy models. The rTg4510 transgenic mouse is characterized by inducible over-expression of P301L mutant tau, and exhibits robust age-dependent brain tau pathology. Systemic treatment with PHF6 and PHF13 from 3 to 6 months of age led to a significant decline in brain and CSF p-tau levels. In a second model, injection of preformed tau fibrils (PFFs) comprised of recombinant tau protein encompassing the microtubule-repeat domains into the cortex and hippocampus of young P301S mutant tau over-expressing mice (PS19) led to robust tau pathology on the ipsilateral side with evidence of spread to distant sites, including the contralateral hippocampus and bilateral entorhinal cortex 4 weeks post-injection. Systemic treatment with PHF13 led to a significant decline in the spread of tau pathology in this model. The reduction in tau species after p-tau antibody treatment was associated with an improvement in novel-object recognition memory test in both models. These studies provide evidence supporting the use of tau immunotherapy as a potential treatment option for AD and other tauopathies.

  19. Tau Proteins Cross the Blood-Brain Barrier.

    PubMed

    Banks, William A; Kovac, Andrej; Majerova, Petra; Bullock, Kristin M; Shi, Min; Zhang, Jing

    2017-01-01

    Tauopathies are a hallmark of many neurodegenerative diseases, including Alzheimer's disease and traumatic brain injuries. It has been demonstrated that amyloid-beta peptides, alpha-synuclein, and prion proteins cross the blood-brain barrier (BBB), contributing to their abilities to induce disease. Very little is known about whether tau proteins can cross the BBB. Here we systematically characterized several key forms of tau proteins to cross the BBB, including Tau-441 (2N4R), Tau-410 (2N3R), truncated tau 151-391 (0N4R), and truncated tau 121-227. All of these tau proteins crossed the BBB readily and bidirectonally; however, only Tau-410 had a saturable component to its influx. The tau proteins also entered the blood after their injection into the brain, with Tau 121-227 having the slowest exit from brain. The tau proteins varied in regards to their enzymatic stability in brain and blood and in their peripheral pharmacokinetics. These results show that blood-borne tau proteins could contribute to brain tauopathies. The result also suggest that the CNS can contribute to blood levels of tau, raising the possibility that, as suggested for other misfolded proteins, blood levels of tau proteins could be used as a biomarker of CNS disease.

  20. Study of the Tau- to Pi- Pi+ Pi- Pi0 Nu/Tau And Tau- to Pi- Pi- Pi+ Eta Nu/Tau Decays Using the BaBar Detector

    SciTech Connect

    Sobie, Randall; /Victoria U.

    2007-11-14

    The {tau}{sup -} {yields} {pi}{sup -}{pi}{sup +}{pi}{sup -}{nu}{sub {tau}} and {tau}{sup -} {yields} {pi}{sup -}{pi}{sup -}{pi}{sup +}{eta}{nu}{sub {tau}} decays have been studied with the BABAR detector. Preliminary branching fractions on the two modes are presented. The {tau}{sup -} {yields} {pi}{sup -}{pi}{sup -}{pi}{sup +}{eta}{nu}{sub {tau}} mode is found to have a large contribution from the {tau}{sup -} {yields} {omega}{pi}{sup -}{nu}{sub {tau}} decay. The {tau}{sup -} {yields} {pi}{sup -}{pi}{sup -}{pi}{sup +}{eta}{nu}{sub {tau}} decay is studied using the {eta} {yields} {gamma}{gamma} mode and the {tau}{sup -} f{sub 1}(1285){pi}{sup -}{nu}{sub {tau}} decay is seen to be the primary source of these decays. A 90% confidence level upper limit is placed on the {tau}{sup -} {yields} {eta}{prime}(958){pi}{sup -}{nu}{sub {tau}} decay which proceeds through a second-class current and is expected to be forbidden in the limit of perfect isospin symmetry.

  1. Horizontal Tau air showers from mountains in deep vally :Traces of Ultrahigh neutrino tau

    NASA Astrophysics Data System (ADS)

    Fargion, Daniele

    1999-08-01

    Ultra High Energy (UHE) Tau neutrino may lead to a very peculiar imprint in future underground K m3 detectors in water and ice as well as in air: rarest secondary tau tracks and decay which may exceed the muon ones. Indeed Bremsstrahlung at high energy lead to longer tracks for heavier leptons. Radiation lenght grows nearly with the square of the lepton mass. Indeed electrons are too light and their trace in matter is negligible (decimeters) muon are much better observed, while tau are too short life time and short range to be found. However, because relativistic time expansion, UHE tau traces in matter, above 1017 eV , are relativistically boosted overcoming the corresponding muon tracks, already bounded by bremsstrahlung logaritmic regime. The tau crossing for Kms in water or ice may be confused with common muon tracks; their tau decay may be missunderstood as muonic catastrophic brehmstrallung interactions. To economize UHE tau dicovery, we suggest to look the tau decay in air into the deep valleys montains, like Canyons or deep in escavation mines where horizontal air showers induce fluoresce or Cerenkov lights. The mountain valley width screens from horizontal secondary muons. The valley height increases the solid angle view. The horizontal air Kms-size gap offer a strong discriminator to filter UHE muons against tau. Tens event a year at PeV ( W resonance peak) energies in K m3 excavation gap should be observable . Hunting air shower in the night toward high mountains in Canyons or in a deep excavation may be the best and cheapest way to discover UHE neutrinos , either born by electron antineutrino scattering on electrons at PeV energies, or by direct tau neutrino possibly relic of muonic flavour oscillation even at EeV energies.

  2. Amplification of Tau fibrils from minute quantities of seeds.

    PubMed

    Meyer, Virginia; Dinkel, Paul D; Rickman Hager, Emily; Margittai, Martin

    2014-09-16

    The propagation of Tau pathology in Alzheimer's disease (AD) is thought to proceed through templated conversion of Tau protein into fibrils and cell-to-cell transfer of elongation-competent seeds. To investigate the efficiency of Tau conversion, we adapted the protein misfolding cyclic amplification assay used for the conversion of prions. Utilizing heparin as a cofactor and employing repetitive cycles of shearing and growth, synthetic Tau fibrils and Tau fibrils in AD brain extract are progressively amplified. Concurrently, self-nucleation is suppressed. The results highlight breakage-induced replication of Tau fibrils as a potential facilitator of disease spread.

  3. Amplification of Tau Fibrils from Minute Quantities of Seeds

    PubMed Central

    2014-01-01

    The propagation of Tau pathology in Alzheimer’s disease (AD) is thought to proceed through templated conversion of Tau protein into fibrils and cell-to-cell transfer of elongation-competent seeds. To investigate the efficiency of Tau conversion, we adapted the protein misfolding cyclic amplification assay used for the conversion of prions. Utilizing heparin as a cofactor and employing repetitive cycles of shearing and growth, synthetic Tau fibrils and Tau fibrils in AD brain extract are progressively amplified. Concurrently, self-nucleation is suppressed. The results highlight breakage-induced replication of Tau fibrils as a potential facilitator of disease spread. PMID:25153692

  4. Surface-skimming stoneflies and mayflies: the taxonomic and mechanical diversity of two-dimensional aerodynamic locomotion.

    PubMed

    Marden, J H; O'Donnell, B C; Thomas, M A; Bye, J Y

    2000-01-01

    The best supported hypothesis for the evolutionary origin of insect wings is that they evolved from articulated, leg-derived respiratory structures of aquatic ancestors. However, there are no fossils of the immediate ancestors of winged insects, and it is difficult to imagine how a functional transition from gills to wings could have occurred. Recent studies of surface-skimming locomotion in stoneflies and mayflies offer a plausible solution by showing how rudimentary wings and muscle power can be used to accomplish two-dimensional aerodynamic locomotion on the surface of water. Here we extend that line of research by examining the phylogenetic distribution and mechanistic diversity of surface skimming in stoneflies, along with a limited examination of mayflies. These investigations reveal both a broad taxonomic occurrence and a fine gradation of mechanically distinct forms. Distinct forms of wing-flapping surface skimming include (1) stoneflies that flap their wings weakly while maintaining their body in contact with the water and undulating their abdomen laterally in a swimming-like motion, (2) stoneflies that skim while elevating their body above the water and maintaining all six legs on the surface, (3) stoneflies and mayflies that skim with only four legs on the water surface, (4) stoneflies that skim with only their two hind legs on the surface, and (5) stoneflies that, beginning with a series of leg motions nearly identical to hind-leg skimmers, use their hind legs to jump from the water into the air to initiate flapping flight. Comparisons across these forms of skimming show that wing-beat amplitude, horizontal velocity, and the verticality of aerodynamic force production increase as the body orientation becomes more upright and contact with the water is minimized. These behaviors illustrate a mechanical pathway by which flying insects could have evolved from swimming ancestors via a series of finely graded intermediate stages. The phylogenetic distribution

  5. (18)F-AV-1451 and CSF T-tau and P-tau as biomarkers in Alzheimer's disease.

    PubMed

    Mattsson, Niklas; Schöll, Michael; Strandberg, Olof; Smith, Ruben; Palmqvist, Sebastian; Insel, Philip S; Hägerström, Douglas; Ohlsson, Tomas; Zetterberg, Henrik; Jögi, Jonas; Blennow, Kaj; Hansson, Oskar

    2017-09-01

    To elucidate the relationship between cerebrospinal fluid (CSF) total-tau (T-tau) and phosphorylated tau (P-tau) with the tau PET ligand (18)F-AV-1451 in Alzheimer's disease (AD), we examined 30 cognitively healthy elderly (15 with preclinical AD), 14 prodromal AD, and 39 AD dementia patients. CSF T-tau and P-tau were highly correlated (R = 0.92, P < 0.001), but they were only moderately associated with retention of (18)F-AV-1451, and mainly in demented AD patients. (18)F-AV-1451, but not CSF T-tau or P-tau, was strongly associated with atrophy and cognitive impairment. CSF tau was increased in preclinical AD, despite normal (18)F-AV-1451 retention. However, not all dementia AD patients exhibited increased CSF tau, even though (18)F-AV-1451 retention was always increased at this disease stage. We conclude that CSF T-tau and P-tau mainly behave as biomarkers of "disease state", since they appear to be increased in many cases of AD at all disease stages, already before the emergence of tau aggregates. In contrast, (18)F-AV-1451 is a biomarker of "disease stage", since it is increased in clinical stages of the disease, and is associated with brain atrophy and cognitive decline. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

  6. Reanalysis and experimental evidence indicate that the earliest trace fossil of a winged insect was a surface-skimming neopteran.

    PubMed

    Marden, James H

    2013-01-01

    A recent description and analysis of an imprint fossil from the Carboniferous concluded that it was made by a mayfly landing in sediment at the edge of water. Here, I reanalyze that trace fossil and supply experimental evidence regarding wing traces and behavior. The thorax of the trace maker lacked structures characteristic of mayflies, but closely matches a modern neopteran insect family (Taeniopterygidae, Plecoptera) little changed from Early Permian fossils. Edges of the folded wings of live Taeniopteryx leave marks on sediment closely matching marks in the trace fossil. Faint marks lateral to and beyond the reach of meso- and metathoracic legs match the location where wings of surface-skimming Taeniopteryx stoneflies lightly touch the sediment when these insects skim onto wet ground at shorelines. Dimensions of the thorax of the trace indicate relatively weak flight ability compared to fossils from the Early Permian, making doubtful the hypothesis that the trace maker was flight capable. Ultimately, this fossil best fits a scenario in which a neopteran insect skimmed across the surface of water, then folded its wings. Surface skimming as a precursor to the evolution of flight in insects is supported by this fossil evidence of skimming behavior in a Carboniferous insect. © 2012 The Author. Evolution© 2012 The Society for the Study of Evolution.

  7. Tau pathology spread in PS19 tau transgenic mice following locus coeruleus (LC) injections of synthetic tau fibrils is determined by the LC's afferent and efferent connections.

    PubMed

    Iba, Michiyo; McBride, Jennifer D; Guo, Jing L; Zhang, Bin; Trojanowski, John Q; Lee, Virginia M-Y

    2015-09-01

    Filamentous tau inclusions are hallmarks of Alzheimer's disease (AD) and other neurodegenerative tauopathies. An increasing number of studies implicate the cell-to-cell propagation of tau pathology in the progression of tauopathies. We recently showed (Iba et al., J Neurosci 33:1024-1037, 2013) that inoculation of preformed synthetic tau fibrils (tau PFFs) into the hippocampus of young transgenic (Tg) mice (PS19) overexpressing human P301S mutant tau induced robust tau pathology in anatomically connected brain regions including the locus coeruleus (LC). Since Braak and colleagues hypothesized that the LC is the first brain structure to develop tau lesions and since LC has widespread connections throughout the CNS, LC neurons could be the critical initiators of the stereotypical spreading of tau pathology through connectome-dependent transmission of pathological tau in AD. Here, we report that injections of tau PFFs into the LC of PS19 mice induced propagation of tau pathology to major afferents and efferents of the LC. Notably, tau pathology propagated along LC efferent projections was localized not only to axon terminals but also to neuronal perikarya, suggesting transneuronal transfer of templated tau pathology to neurons receiving LC projections. Further, brainstem neurons giving rise to major LC afferents also developed perikaryal tau pathology. Surprisingly, while tangle-bearing neurons degenerated in the LC ipsilateral to the injection site starting 6 months post-injection, no neuron loss was seen in the contralateral LC wherein tangle-bearing neurons gradually cleared tau pathology by 6-12 months post-injection. However, the spreading pattern of tau pathology observed in our LC-injected mice is different from that in AD brains since hippocampus and entorhinal cortex, which are affected in early stages of AD, were largely spared of tau inclusions in our model. Thus, while our study tested critical aspects of the Braak hypothesis of tau pathology spread

  8. A physicochemical investigation of membrane fouling in cold microfiltration of skim milk.

    PubMed

    Tan, T J; Wang, D; Moraru, C I

    2014-01-01

    The main challenge in microfiltration (MF) is membrane fouling, which leads to a significant decline in permeate flux and a change in membrane selectivity over time. This work aims to elucidate the mechanisms of membrane fouling in cold MF of skim milk by identifying and quantifying the proteins and minerals involved in external and internal membrane fouling. Microfiltration was conducted using a 1.4-μm ceramic membrane, at a temperature of 6±1°C, cross-flow velocity of 6m/s, and transmembrane pressure of 159kPa, for 90min. Internal and external foulants were extracted from a ceramic membrane both after a brief contact between the membrane and skim milk, to evaluate instantaneous adsorption of foulants, and after MF. Four foulant streams were collected: weakly attached external foulants, weakly attached internal foulants, strongly attached external foulants, and strongly attached internal foulants. Liquid chromatography coupled with tandem mass spectrometry analysis showed that all major milk proteins were present in all foulant streams. Proteins did appear to be the major cause of membrane fouling. Proteomics analysis of the foulants indicated elevated levels of serum proteins as compared with milk in the foulant fractions collected from the adsorption study. Caseins were preferentially introduced into the fouling layer during MF, when transmembrane pressure was applied, as confirmed both by proteomics and mineral analyses. The knowledge generated in this study advances the understanding of fouling mechanisms in cold MF of skim milk and can be used to identify solutions for minimizing membrane fouling and increasing the efficiency of milk MF. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  9. Utilization of konjac glucomannan as a fat replacer in low-fat and skimmed yogurt.

    PubMed

    Dai, Shuhong; Corke, Harold; Shah, Nagendra P

    2016-09-01

    Konjac glucomannan (KGM) has been reported to be beneficial to human health, as well as having potential functional properties as a fat replacer in dairy products. In this study, 0.5% KGM solution was added to prepare low-fat (LFKGM) and skimmed (SKKGM) yogurts, and their physicochemical properties were compared with those of full-fat yogurt control (FFC), low-fat yogurt control (LFC), and skimmed yogurt control (SKC). Properties and composition were determined and the microscopic structures of all yogurts were observed during storage at 4°C for 21d. Generally, addition of KGM to yogurts had no significant effect on composition, pH, and titratable acidity at each storage day. The LFKGM and SKKGM had higher whiteness, greenness, and yellowness hues compared with those of the LFC and SKC. The proteolysis of LFKGM and SKKGM was similar to that of FFC, whereas it was lower than in LFC and SKC after 14d of storage. Addition of KGM had no positive effects on the water-holding capacity, but led to a decrease in syneresis and spontaneous whey separation in LFKGM and SKKGM compared with those of LFC and SKC. The spontaneous whey separation of LFKGM was similar to that of FFC. Presence of KGM in skimmed yogurt affected textural characteristics, while having little effect on texture of low-fat yogurt. Additionally, LFKGM and SKKGM showed stronger and more stable gel structures than those of FFC, LFC, and SKC. Overall, no substantial changes were found in the characteristics for each yogurt during storage, except for pH and gel structures. Results indicated that KGM may be a good fat replacer to develop reduced-fat yogurts with desired characteristics. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  10. Potential and pitfalls of eukaryotic metagenome skimming: a test case for lichens.

    PubMed

    Greshake, Bastian; Zehr, Simonida; Dal Grande, Francesco; Meiser, Anjuli; Schmitt, Imke; Ebersberger, Ingo

    2016-03-01

    Whole-genome shotgun sequencing of multispecies communities using only a single library layout is commonly used to assess taxonomic and functional diversity of microbial assemblages. Here, we investigate to what extent such metagenome skimming approaches are applicable for in-depth genomic characterizations of eukaryotic communities, for example lichens. We address how to best assemble a particular eukaryotic metagenome skimming data, what pitfalls can occur, and what genome quality can be expected from these data. To facilitate a project-specific benchmarking, we introduce the concept of twin sets, simulated data resembling the outcome of a particular metagenome sequencing study. We show that the quality of genome reconstructions depends essentially on assembler choice. Individual tools, including the metagenome assemblers Omega and MetaVelvet, are surprisingly sensitive to low and uneven coverages. In combination with the routine of assembly parameter choice to optimize the assembly N50 size, these tools can preclude an entire genome from the assembly. In contrast, MIRA, an all-purpose overlap assembler, and SPAdes, a multisized de Bruijn graph assembler, facilitate a comprehensive view on the individual genomes across a wide range of coverage ratios. Testing assemblers on a real-world metagenome skimming data from the lichen Lasallia pustulata demonstrates the applicability of twin sets for guiding method selection. Furthermore, it reveals that the assembly outcome for the photobiont Trebouxia sp. falls behind the a priori expectation given the simulations. Although the underlying reasons remain still unclear, this highlights that further studies on this organism require special attention during sequence data generation and downstream analysis. © 2015 John Wiley & Sons Ltd.

  11. Are Colombian sickness funds cream skimming enrollees? An analysis with suggestions for policy improvement.

    PubMed

    Trujillo, Antonio J; McCalla, Dawn C

    2004-08-01

    One of the primary objectives of Colombian social health insurance reform was to increase competition among for-profit insurers. Unfortunately, the flat capitated formula creates an opportunity for sickness funds to maximize reimbursement gains by cream skimming--selecting against unhealthy individuals. This paper explores sickness fund selection behavior to evaluate the efficiency losses associated with the introduction of managed competition in Colombia. Data from a 1997 Colombian household survey are analyzed with a bivariate probit model with partial observability using instrumental variables. The model yields some evidence of sickness fund selection based on health status. Public policy options to discourage risk selection by health status are discussed.

  12. Synthesis of Carbon Nanotube and Its Potential Application in Protein Purification by Using Skim Latex Serum

    NASA Astrophysics Data System (ADS)

    Mujawar, N. M.; Yusof, F.; Alkhatib, M. F.; Muataz, A. A.; Qudsieh, I. Y.; Mohammed, A. Al Saadi; Khalid, M.

    2009-06-01

    Carbon nanotubes (CNTs) have been synthesized by a gas phase double stage chemical vapor deposition (DS-CVD) technique using acetylene (C2H2) and hydrogen (H2) as precursor gases. The morphology and the structure of CNTs were characterized using field emission scanning electron microscope (FSEM) and transmission electron microscope (TEM). The CNTs produced were purified and functionalized by using covalent functionalization methods. The functionalized CNTs were used as column chromatographic media for skim latex protein purification. In this process, pH and ionic strength were optimized to achieve higher efficiency in protein purification.

  13. Systems engineering study: tank 241-C-103 organic skimming,storage, treatment and disposal options

    SciTech Connect

    Klem, M.J.

    1996-10-23

    This report evaluates alternatives for pumping, storing, treating and disposing of the separable phase organic layer in Hanford Site Tank 241-C-103. The report provides safety and technology based preferences and recommendations. Two major options and several varations of these options were identified. The major options were: 1) transfer both the organic and pumpable aqueous layers to a double-shell tank as part of interim stabilization using existing salt well pumping equipment or 2) skim the organic to an above ground before interim stabilization of Tank 241-C-103. Other options to remove the organic were considered but rejected following preliminary evaluation.

  14. Modulation of tau phosphorylation and intracellular localization by cellular stress.

    PubMed Central

    Jenkins, S M; Zinnerman, M; Garner, C; Johnson, G V

    2000-01-01

    Tau is a microtubule-associated protein that is functionally modulated by phosphorylation and hyperphosphorylated in several neurodegenerative diseases. Because phosphorylation regulates both normal and pathological tau functioning, it is of great interest to identify the signalling pathways and enzymes capable of modulating tau phosphorylation in vivo. The present study examined changes in tau phosphorylation and localization in response to osmotic stress, which activates the stress-activated protein kinases (SAPKs), a family of proline-directed protein kinases shown to phosphorylate tau in vitro and hypothesized to phosphorylate tau in Alzheimer's disease. Immunoblot analysis with phosphorylation-dependent antibodies revealed that osmotic stress increased tau phosphorylation at the non-Ser/Thr-Pro sites Ser-262/356, within the microtubule-binding domain, as well as Ser/Thr-Pro sites outside of tau's microtubule-binding domain. Although all SAPKs examined were activated by osmotic stress, none of the endogenous SAPKs mediated the increase in tau phosphorylation. However, when transfected into SH-SY5Y cells, SAPK3, but not the other SAPKs examined, phosphorylated tau in situ in response to activation by osmotic stress. Osmotic-stress-induced tau phosphorylation correlated with a decrease in the amount of tau associated with the cytoskeleton and an increase in the amount of soluble tau. This stress-induced alteration in tau localization was only partially due to phosphorylation at Ser-262/356 by a staurosporine-sensitive, non-proline-directed, protein kinase. Taken together, these results suggest that osmotic stress activates at least two tau-directed protein kinases, one proline-directed and one non-proline-directed, that SAPK3 can phosphorylate tau on Ser/Thr-Pro residues in situ, and that Ser-262/356 phosphorylation only partially regulates tau localization in the cell. PMID:10620503

  15. Aminothienopyridazines and methylene blue affect Tau fibrillization via cysteine oxidation.

    PubMed

    Crowe, Alex; James, Michael J; Lee, Virginia M-Y; Smith, Amos B; Trojanowski, John Q; Ballatore, Carlo; Brunden, Kurt R

    2013-04-19

    Alzheimer disease and several other neurodegenerative disorders are characterized by the accumulation of intraneuronal fibrils comprised of the protein Tau. Tau is normally a soluble protein that stabilizes microtubules, with splice isoforms that contain either three (3-R) or four (4-R) microtubule binding repeats. The formation of Tau fibrils is thought to result in neuronal damage, and inhibitors of Tau fibrillization may hold promise as therapeutic agents. The process of Tau fibrillization can be replicated in vitro, and a number of small molecules have been identified that inhibit Tau fibril formation. However, little is known about how these molecules affect Tau fibrillization. Here, we examined the mechanism by which the previously described aminothieno pyridazine (ATPZ) series of compounds inhibit Tau fibrillization. Active ATPZs were found to promote the oxidation of the two cysteine residues within 4-R Tau by a redox cycling mechanism, resulting in the formation of a disulfide-containing compact monomer that was refractory to fibrillization. Moreover, the ATPZs facilitated intermolecular disulfide formation between 3-R Tau monomers, leading to dimers that were capable of fibrillization. The ATPZs also caused cysteine oxidation in molecules unrelated to Tau. Interestingly, methylene blue, an inhibitor of Tau fibrillization under evaluation in Alzheimer disease clinical trials, caused a similar oxidation of cysteines in Tau and other molecules. These findings reveal that the ATPZs and methylene blue act by a mechanism that may affect their viability as potential therapeutic agents.

  16. Aminothienopyridazines and Methylene Blue Affect Tau Fibrillization via Cysteine Oxidation*

    PubMed Central

    Crowe, Alex; James, Michael J.; Lee, Virginia M.-Y.; Smith, Amos B.; Trojanowski, John Q.; Ballatore, Carlo; Brunden, Kurt R.

    2013-01-01

    Alzheimer disease and several other neurodegenerative disorders are characterized by the accumulation of intraneuronal fibrils comprised of the protein Tau. Tau is normally a soluble protein that stabilizes microtubules, with splice isoforms that contain either three (3-R) or four (4-R) microtubule binding repeats. The formation of Tau fibrils is thought to result in neuronal damage, and inhibitors of Tau fibrillization may hold promise as therapeutic agents. The process of Tau fibrillization can be replicated in vitro, and a number of small molecules have been identified that inhibit Tau fibril formation. However, little is known about how these molecules affect Tau fibrillization. Here, we examined the mechanism by which the previously described aminothieno pyridazine (ATPZ) series of compounds inhibit Tau fibrillization. Active ATPZs were found to promote the oxidation of the two cysteine residues within 4-R Tau by a redox cycling mechanism, resulting in the formation of a disulfide-containing compact monomer that was refractory to fibrillization. Moreover, the ATPZs facilitated intermolecular disulfide formation between 3-R Tau monomers, leading to dimers that were capable of fibrillization. The ATPZs also caused cysteine oxidation in molecules unrelated to Tau. Interestingly, methylene blue, an inhibitor of Tau fibrillization under evaluation in Alzheimer disease clinical trials, caused a similar oxidation of cysteines in Tau and other molecules. These findings reveal that the ATPZs and methylene blue act by a mechanism that may affect their viability as potential therapeutic agents. PMID:23443659

  17. Study of the tau- ---> pi- pi- pi+ pi0 pi0 nu/tau and tau- --> 3h- 2h+ nu/tau Decays Using the BaBar Detector

    SciTech Connect

    Sobie, R.; /Victoria U.

    2005-06-21

    The {tau}{sup -} {yields} {pi}{sup -}{pi}{sup -}{pi}{sup +}{pi}{sup 0}{pi}{sup 0}{nu}{sub {tau}} and {tau}{sup -} {yields} 3h{sup -} 2h{sup +} {nu}{sub {tau}} decays have been studied using the BABAR experiment at the PEP-II e{sup +}e{sup -} storage ring. Preliminary branching fractions are given for the {tau}{sup -} {yields} {pi}{sup -}{pi}{sup -}{pi}{sup +}{pi}{sup 0}{pi}{sup 0}{nu}{sub {tau}} and to the sub-channels {tau}{sup -} {yields} {eta}{pi}{sup -} {pi}{sup 0}{nu}{sub {tau}} and {tau}{sup -} {yields} {omega}(782){pi}{sup -}{pi}{sup 0}{nu}{sub {tau}}. A preliminary upper limit is given on the branching fraction for the {phi}(1020){pi}{sup -}{pi}{sup 0}{nu}{sub {tau}} mode. In addition a preliminary measurement of the branching fraction of the {tau}{sup -} {yields} 3h{sup -}2h{sup +} {nu}{sub {tau}} decay (h = {pi}, K) is presented.

  18. PICALM modulates autophagy activity and tau accumulation

    PubMed Central

    Moreau, Kevin; Fleming, Angeleen; Imarisio, Sara; Lopez Ramirez, Ana; Mercer, Jacob L.; Jimenez-Sanchez, Maria; Bento, Carla F.; Puri, Claudia; Zavodszky, Eszter; Siddiqi, Farah; Lavau, Catherine P.; Betton, Maureen; O’Kane, Cahir J.; Wechsler, Daniel S.; Rubinsztein, David C.

    2014-01-01

    Genome-wide association studies have identified several loci associated with Alzheimer’s disease (AD), including proteins involved in endocytic trafficking such as PICALM/CALM (phosphatidylinositol binding clathrin assembly protein). It is unclear how these loci may contribute to AD pathology. Here we show that CALM modulates autophagy and alters clearance of tau, a protein which is a known autophagy substrate and which is causatively linked to AD, both in vitro and in vivo. Furthermore, altered CALM expression exacerbates tau-mediated toxicity in zebrafish transgenic models. CALM influences autophagy by regulating the endocytosis of SNAREs, such as VAMP2, VAMP3 and VAMP8, which have diverse effects on different stages of the autophagy pathway, from autophagosome formation to autophagosome degradation. This study suggests that the AD genetic risk factor CALM modulates autophagy, and this may affect disease in a number of ways including modulation of tau turnover. PMID:25241929

  19. Riluzole Rescues Glutamate Alterations, Cognitive Deficits, and Tau Pathology Associated with P301L Tau Expression

    PubMed Central

    Hunsberger, Holly C.; Weitzner, Daniel S; Rudy, Carolyn C.; Hickman, James E.; Libell, Eric M.; Speer, Rebecca R.; Gerhardt, Greg A.; Reed, Miranda N.

    2016-01-01

    In the years preceding a diagnosis of Alzheimer’s disease (AD), hyperexcitability of the hippocampus is a commonly observed phenomenon in those at risk for AD. Our previous work suggests a dysregulation in glutamate neurotransmission may mediate this hyperexcitability, and glutamate dysregulation correlates with cognitive deficits in the rTg(TauP301L)4510 mouse model of AD. To determine whether improving glutamate regulation would attenuate cognitive deficits and AD-related pathology, TauP301L mice were treated with riluzole (~ 12.5 mg/kg/day p.o.), an FDA-approved drug for ALS that lowers extracellular glutamate levels. Riluzole-treated TauP301L mice exhibited improved memory performance that was associated with a decrease in glutamate release and an increase in glutamate uptake in the dentate gyrus (DG), cornu ammonis 3(CA3), and cornu ammonis 1(CA1) regions of the hippocampus. Riluzole treatment also attenuated the TauP301L-mediated increase in hippocampal vesicular glutamate transporter (vGLUT1), and the TauP301L-mediated decrease in hippocampal glutamate transporter 1 (GLT-1) and PSD-95 expression. Riluzole treatment also reduced tau pathology. These findings further elucidate the changes in glutamate regulation associated with tau pathology and open new opportunities for the development of clinically applicable therapeutic approaches to regulate glutamate in vulnerable circuits for those at risk for the development of AD. PMID:26146790

  20. CP violation in semileptonic tau lepton decays

    SciTech Connect

    Delepine, D.; Castro, G. Lopez; Lozano, L.-T. Lopez

    2005-08-01

    The leading order contribution to the direct CP asymmetry in {tau}{sup {+-}}{yields}K{sup {+-}}{pi}{sup 0}{nu}{sub {tau}} decay rates is evaluated within the standard model. The weak phase required for CP violation is introduced through an interesting mechanism involving second order weak interactions, which is also responsible for tiny violations of the {delta}S={delta}Q rule in K{sub l3} decays. The calculated CP asymmetry turns out to be of order 10{sup -12}, leaving a large window for studying effects of nonstandard sources of CP violation in this observable.

  1. A measurement of the tau lifetime

    NASA Astrophysics Data System (ADS)

    Abreu, P.; Adam, W.; Adye, T.; Agasi, E.; Aleksan, R.; Alekseev, G. D.; Algeri, A.; Allen, P.; Almehed, S.; Alvsvaag, S. J.; Amaldi, U.; Anassontzis, E. G.; Andreazza, A.; Antilogus, P.; Apel, W.-D.; Apsimon, R. J.; Arnoud, Y.; Å, B.; Augustin, J.-E.; Augustinus, A.; Baillon, P.; Bambade, P.; Barao, F.; Barate, R.; Barbiellini, G.; Bardin, D. Y.; Barker, G. J.; Baroncelli, A.; Barring, O.; Barrio, J. A.; Bartl, W.; Bates, M. J.; Battaglia, M.; Baubillier, M.; Becks, K.-H.; Beeston, C. J.; Begalli, M.; Beilliere, P.; Belokopytov, Yu.; Beltran, P.; Benedic, D.; Benvenuti, A. C.; Berggren, M.; Bertrand, D.; Bianchi, F.; Bilenky, M. S.; Billoir, P.; Bjarne, J.; Bloch, D.; Blyth, S.; Bocci, V.; Bogolubov, P. N.; Bolognese, T.; Bonesini, M.; Bonivento, W.; Booth, P. S. L.; Borisov, G.; Borner, H.; Bosio, C.; Bostjancic, B.; Bosworth, S.; Botner, O.; Bouquet, B.; Bourdarios, C.; Bowcock, T. J. V.; Bozzo, M.; Braibant, S.; Branchini, P.; Brand, K. D.; Brenner, R. A.; Briand, H.; Bricman, C.; Brown, R. C. A.; Brummer, N.; Brunet, J.-M.; Bugge, L.; Buran, T.; Burmeister, H.; Buytaert, J. A. M. A.; Caccia, M.; Calvi, M.; Camacho Rozas, A. J.; Campion, R.; Camporesi, T.; Canale, V.; Cao, F.; Carena, F.; Carroll, L.; Castillo Gimenez, M. V.; Cattai, A.; Cavallo, F. R.; Cerrito, L.; Chabaud, V.; Chan, A.; Charpentier, Ph.; Chaussard, L.; Chauveau, J.; Checchia, P.; Chelkov, G. A.; Chevalier, L.; Chliapnikov, P.; Chorowicz, V.; Chrin, J. T. M.; Clara, M. P.; Collins, P.; Contreras, J. L.; Contri, R.; Cortina, E.; Cosme, G.; Couchot, F.; Crawley, H. B.; Crennell, D.; Crosetti, G.; Crozon, M.; Cuevas Maestro, J.; Czellar, S.; Dahl-Jensen, E.; Dalmagne, B.; Dam, M.; Damgaard, G.; Darbo, G.; Daubie, E.; Daum, A.; Dauncey, P. D.; Davenport, M.; David, P.; Davies, J.; da Silva, W.; Defoix, C.; Delpierre, P.; Demaria, N.; de Angelis, A.; de Boeck, H.; de Boer, W.; de Clercq, C.; de Fez Laso, M. D. M.; de Groot, N.; de La Vaissiere, C.; de Lotto, B.; de Min, A.; Dijkstra, H.; di Ciaccio, L.; Djama, F.; Dolbeau, J.; Donszelmann, M.; Doroba, K.; Dracos, M.; Drees, J.; Dris, M.; Dufour, Y.; Dupont, F.; Eek, L.-O.; Eerola, P. A.-M.; Ehret, R.; Ekelof, T.; Ekspong, G.; Elliot Peisert, A.; Engel, J.-P.; Ershaidat, N.; Fassouliotis, D.; Feindt, M.; Fenyuk, A.; Fernandez Alonso, M.; Ferrer, A.; Filippas, T. A.; Firestone, A.; Foeth, H.; Fokitis, E.; Fontanelli, F.; Forbes, K. A. J.; Fousset, J.-L.; Francon, S.; Franek, B.; Frenkiel, P.; Fries, D. C.; Frodesen, A. G.; Fruhwirth, R.; Fulda-Quenzer, F.; Furnival, K.; Furstenau, H.; Fuster, J.; Gamba, D.; Garcia, C.; Garcia, J.; Gaspar, C.; Gasparini, U.; Gavillet, Ph.; Gazis, E. N.; Gerber, J.-P.; Giacomelli, P.; Gokieli, R.; Golob, B.; Golovatyuk, V. M.; Gomez Y Cadenas, J. J.; Goobar, A.; Gopal, G.; Gorski, M.; Gracco, V.; Grant, A.; Grard, F.; Graziani, E.; Grosdidier, G.; Gross, E.; Grosse-Wiesmann, P.; Grossetete, B.; Gumenyuk, S.; Guy, J.; Haedinger, U.; Hahn, F.; Hahn, M.; Haider, S.; Hajduk, Z.; Hakansson, A.; Hallgren, A.; Hamacher, K.; Hamel de Monchenault, G.; Hao, W.; Harris, F. J.; Hedberg, V.; Henkes, T.; Hernandez, J. J.; Herquet, P.; Herr, H.; Hessing, T. L.; Hietanen, I.; Higgins, C. O.; Higon, E.; Hilke, H. J.; Hodgson, S. D.; Hofmokl, T.; Holmes, R.; Holmgren, S.-O.; Holthuizen, D.; Honore, P. F.; Hooper, J. E.; Houlden, M.; Hrubec, J.; Huet, K.; Hulth, P. O.; Hultqvist, K.; Ioannou, P.; Iversen, P.-S.; Jackson, J. N.; Jalocha, P.; Jarlskog, G.; Jarry, P.; Jean-Marie, B.; Johansson, E. K.; Johnson, D.; Jonker, M.; Jonsson, L.; Juillot, P.; Kalkanis, G.; Kalmus, G.; Kapusta, F.; Karlsson, M.; Karvelas, E.; Katsanevas, S.; Katsoufis, E. C.; Keranen, R.; Kesteman, J.; Khomenko, B. A.; Khovanski, N. N.; King, B.; Kjaer, N. J.; Klein, H.; Klovning, A.; Kluit, P.; Koch-Mehrin, A.; Koehne, J. H.; Koene, B.; Kokkinias, P.; Koratzinos, M.; Korcyl, K.; Korytov, A. V.; Kostioukhine, V.; Kourkoumelis, C.; Kouznetsov, O.; Kramer, P. H.; Krolikowski, J.; Kronkvist, I.; Kruener-Marquis, U.; Kucewicz, W.; Kulka, K.; Kurvinen, K.; Lacasta, C.; Lambropoulos, C.; Lamsa, J. W.; Lanceri, L.; Lapin, V.; Laugier, J.-P.; Lauhakangas, R.; Leder, G.; Ledroit, F.; Leitner, R.; Lemoigne, Y.; Lemonne, J.; Lenzen, G.; Lepeltier, V.; Lesiak, T.; Levy, J. M.; Lieb, E.; Liko, D.; Lindgren, J.; Lindner, R.; Lipniacka, A.; Lippi, I.; Loerstad, B.; Lokajicek, M.; Loken, J. G.; Lopez-Fernandez, A.; Lopez Aguera, M. A.; Los, M.; Loukas, D.; Lozano, J. J.; Lutz, P.; Lyons, L.; Maehlum, G.; Maillard, J.; Maio, A.; Maltezos, A.; Mandl, F.; Marco, J.; Margoni, M.; Marin, J.-C.; Markou, A.; Maron, T.; Marti, S.; Mathis, L.; Matorras, F.; Matteuzzi, C.; Matthiae, G.; Mazzucato, M.; Mc Cubbin, M.; Mc Nay, R.; Mc Nulty, R.; Meola, G.; Meroni, C.; Meyer, W. T.; Michelotto, M.; Mikulec, I.; Mirabito, L.; Mitaroff, W. A.; Mitselmakher, G. V.; Mjoernmark, U.; Moa, T.; Moeller, R.; Moenig, K.; Monge, M. R.; Morettini, P.; Mueller, H.; Murray, W. J.; Myatt, G.; Navarria, F. L.; Negri, P.; Nielsen, B. S.; Nijjhar, B.; Nikolaenko, V.; Nilsen, P. E. S.; Niss, P.; Obraztsov, V.; Olshevski, A. G.; Orava, R.; Ostankov, A.; Osterberg, K.; Ouraou, A.; Paganoni, M.; Pain, R.; Papadopoulou, Th. D.; Pape, L.; Parodi, F.; Passeri, A.; Pegoraro, M.; Pennanen, J.; Peralta, L.; Pernegger, H.; Pernicka, M.; Perrotta, A.; Petridou, C.; Petrolini, A.; Pettersen, T. E.; Pierre, F.; Pimenta, M.; Pingot, O.; Plaszczynski, S.; Podobrin, O.; Pol, M. E.; Polok, G.; Poropat, P.; Privitera, P.; Pullia, A.; Radojicic, D.; Ragazzi, S.; Rahmani, H.; Ratoff, P. N.; Read, A. L.; Redaelli, N. G.; Regler, M.; Reid, D.; Renton, P. B.; Resvanis, L. K.; Richard, F.; Richardson, M.; Ridky, J.; Rinaudo, G.; Roditi, I.; Romero, A.; Roncagliolo, I.; Ronchese, P.; Ronnqvist, C.; Rosenberg, E. I.; Rossi, S.; Rossi, U.; Rosso, E.; Roudeau, P.; Rovelli, T.; Ruckstuhl, W.; Ruhlmann-Kleider, V.; Ruiz, A.; Rybin, A.; Saarikko, H.; Sacquin, Y.; Sajot, G.; Salt, J.; Sanchez, J.; Sannino, M.; Schael, S.; Schneider, H.; Schulze, B.; Schyns, M. A. E.; Sciolla, G.; Scuri, F.; Segar, A. M.; Seitz, A.; Sekulin, R.; Sessa, M.; Sette, G.; Seufert, R.; Shellard, R. C.; Siccama, I.; Siegrist, P.; Simonetti, S.; Simonetto, F.; Sisakian, A. N.; Skjevling, G.; Smadja, G.; Smith, G. R.; Sosnowski, R.; Souza-Santos, D.; Spassoff, T. S.; Spiriti, E.; Squarcia, S.; Staeck, H.; Stanescu, C.; Stapnes, S.; Stavropoulos, G.; Stichelbaut, F.; Stocchi, A.; Strauss, J.; Straver, J.; Strub, R.; Stugu, B.; Szczekowski, M.; Szeptycka, M.; Szymanski, P.; Tabarelli, T.; Tchikilev, O.; Theodosiou, G. E.; Tilquin, A.; Timmermans, J.; Timofeev, V. G.; Tkatchev, L. G.; Todorov, T.; Toet, D. Z.; Toker, O.; Tome, B.; Torassa, E.; Tortora, L.; Treille, D.; Trevisan, U.; Trischuk, W.; Tristram, G.; Troncon, C.; Tsirou, A.; Tsyganov, E. N.; Turluer, M.-L.; Tuuva, T.; Tyapkin, I. A.; Tyndel, M.; Tzamarias, S.; Ueberschaer, S.; Ullaland, O.; Uvarov, V.; Valenti, G.; Vallazza, E.; Valls Ferrer, J. A.; Vander Velde, C.; van Apeldoorn, G. W.; van Dam, P.; van der Heijden, M.; van Doninck, W. K.; Vaz, P.; Vegni, G.; Ventura, L.; Venus, W.; Verbeure, F.; Verlato, M.; Vertogradov, L. S.; Vilanova, D.; Vincent, P.; Vitale, L.; Vlasov, E.; Vodopyanov, A. S.; Vollmer, M.; Voulgaris, G.; Voutilainen, M.; Vrba, V.; Wahlen, H.; Walck, C.; Waldner, F.; Wayne, M.; Wehr, A.; Weierstall, M.; Weilhammer, P.; Werner, J.; Wetherell, A. M.; Wickens, J. H.; Wilkinson, G. R.; Williams, W. S. C.; Winter, M.; Witek, M.; Wormser, G.; Woschnagg, K.; Yamdagni, N.; Yepes, P.; Zaitsev, A.; Zalewska, A.; Zalewski, P.; Zavrtanik, D.; Zevgolatakos, E.; Zhang, G.; Zimin, N. I.; Zito, M.; Zuberi, R.; Zukanovich Funchal, R.; Zumerle, G.; Zuniga, J.

    1993-03-01

    The tau lepton lifetime is measured using four different methods with the DELPHI detector. Three measurements using one prong decays are combined, accounting for correlations, resulting in ττ=298 +/-7 (stat.)+/-4 (syst.) fs while the decay length distribution of three prong decays gives ππ=298+/-13 (stat)+/-(syst.) fs. The combined result is ττ=298+/-7 fs. The ratio of the Fermi coupling constant from tau decay relative to that from muon decay is found to be 0.985+/-0.013, compatible with lepton universality.

  2. Search for Second-Class Currents in tau- -> omega.pi-.nu_tau

    SciTech Connect

    Aubert, B.

    2009-04-22

    We report an analysis of {tau}{sup -} decaying into {omega}{pi}{sup -} {nu}{sub {tau}} with {omega} {yields} {pi}{sup +}{pi}{sup -}{pi}{sup 0} using a data sample containing nearly 320 million {tau} pairs collected with the BABAR detector at the PEP-II B-Factory. We find no evidence for second-class currents and we set an upper limit of 0.69% at 90% confidence level for the fraction of second-class currents in this decay mode.

  3. The Tau Lepton and the Search for New Elementary Particle Physics

    SciTech Connect

    Perl, Martin L.

    1998-11-18

    This Fifth International WEIN Symposium is devoted to physics beyond the standard model. This talk is about tau lepton physics, but I begin with the question: do we know how to find new physics in the world of elementary particles? This question is interwoven with the various tau physics topics. These topics are: searching for unexpected tau decay modes; searching for additional tau decay mechanisms; radiative tau decays; tau decay modes of the W, B, and D; decay of the Z{sup 0} to tau pairs; searching for CP violation in tau decay; the tau neutrino, dreams and odd ideas in tau physics; and tau research facilities in the next decades.

  4. Multiple-neutral-meson decays of the /tau/ lepton and electromagnetic calorimeter requirements at Tau-Charm Factory

    SciTech Connect

    Gan, K.K.

    1989-08-01

    This is a study of the physics sensitivity to the multiple-neutral-meson decays of the /tau/ lepton at the Tau-Charm Factory. The sensitivity is compared for a moderate and an ultimate electromagnetic calorimeter. With the high luminosity of the Tau- Charm Factory, a very large sample of the decays /tau//sup /minus// /yields/ /pi//sup /minus//2/pi//sup 0//nu//sub /tau// and /tau//sup /minus// /yields/ /pi//sup /minus//3/pi//sup 0//nu//sub /tau// can be collected with both detectors. However, with the ultimate detector, 2/pi//sup 0/ and 3/pi//sup 0/ can be unambiguously reconstructed with very little background. For the suppressed decay /tau//sup /minus// /yields/ /pi//sup /minus///eta//pi//sup 0//nu//sub /tau//, only the ultimate detector has the sensitivity. The ultimate detector is also sensitive to the more suppressed decay /tau//sup /minus// /yields/ K/sup /minus///eta//nu//sub /tau// and the moderate detector may have the sensitivity if the hadronic background is not significantly larger than that predicted by Lund. In the case of the highly suppressed second-class-current decay /tau//sup /minus// /yields/ /pi//sup /minus///eta//nu//sub /tau//, only the ultimate detector has sensitivity. The sensitivity can be greatly enhanced with a small-angle photon veto. 16 refs., 9 figs., 2 tabs.

  5. Effect of high-pressure homogenisation on rheological properties of rennet-induced skim milk and standardised milk gels.

    PubMed

    Lodaite, Kristina; Chevalier, François; Armaforte, Emanuele; Kelly, Alan L

    2009-08-01

    The effects of high-pressure homogenisation (HPH) in the pressure range 100-300 MPa on the gel formation and rheological properties of rennet-induced skim milk (0.08%, fat, w/w) and standardised milk (3.60% fat, w/w) gels at pH 6.60 were studied. The average casein micelle size in skim milk was significantly reduced and the gel formation time decreased when skim milk was subjected to the pressures of 200 and 300 MPa. The storage modulus of rennet-induced skim milk gels at 2700 s after rennet addition was higher for samples homogenised at higher pressures, which contained smaller casein particles. HPH had little effect on the large deformation properties of rennet-induced skim milk gels. The gel formation time of renneted standardised milk was significantly reduced as a result of HPH, while the storage modulus of rennet-induced milk gels 2700 s after rennet addition increased with increasing homogenising pressure. The apparent fracture stress was slightly higher for standardised milk gels formed from HPH-treated milk, whereas the apparent strain at fracture was lower, than that of unhomogenised milk. In conclusion, HPH treatment influenced gel formation processes of skim milk and its small-deformation rheological properties, mainly through modification of casein micelles. HPH also significantly affected the gel formation process of standardised milk gels and its rheological properties as a result of an increase in volume fraction of aggregating particles, while the particle size was of lesser importance.

  6. Tau Phosphorylation by GSK3 in Different Conditions

    PubMed Central

    Avila, Jesús; León-Espinosa, Gonzalo; García, Esther; García-Escudero, Vega; Hernández, Félix; DeFelipe, Javier

    2012-01-01

    Almost a 20% of the residues of tau protein are phosphorylatable amino acids: serine, threonine, and tyrosine. In this paper we comment on the consequences for tau of being a phosphoprotein. We will focus on serine/threonine phosphorylation. It will be discussed that, depending on the modified residue in tau molecule, phosphorylation could be protective, in processes like hibernation, or toxic like in development of those diseases known as tauopathies, which are characterized by an hyperphosphorylation and aggregation of tau. PMID:22675648

  7. Photoprotection of vitamins in skimmed milk by an aqueous soluble lycopene-gum Arabic microcapsule.

    PubMed

    Montenegro, Mariana A; Nunes, Itaciara L; Mercadante, Adriana Z; Borsarelli, Claudio D

    2007-01-24

    Riboflavin (Rf)-mediated photosensitized degradation of vitamins A and D3 in skimmed milk under illumination with a white fluorescence lamp was studied by using the HPLC technique. The photosensitized degradation of both vitamins followed first-order kinetics, and the temperature effect on the observed photodegradation rate constant allowed the determination of the activation energy Ea as being 4 and 16 kcal/mol for vitamins A and D3, respectively. The addition of lycopene microencapsulated by spray-drying with a gum arabic-sucrose (8:2) mixture (MIC) produced a reduction of ca. 45% in the photosensitized degradation rate of both vitamins. Front-face fluorescence experiments showed the same photoprotection factor in the degradation of Rf itself, indicating that the photodegradation mechanism involved Rf-mediated reactive species, such as the excited triplet state of Rf, 3Rf*, and/or singlet molecular oxygen, 1O2. The interaction of both 3Rf* and 1O2 with MIC was evaluated in aqueous solutions by using laser-induced time-resolved absorption or emission spectroscopy, and the contribution of an inner-filter effect in the presence of MIC in skimmed milk was evaluated by diffuse reflectance spectroscopy. The main operating mechanism of photoprotection is due to the deactivation of 3Rf* by the proteic component of gum arabic; thus, gum arabic based microcapsules could be used to improve the photostability of milk during its storage and/or processing under light.

  8. A method for determining beta-galactosidase activity of yogurt cultures in skim milk.

    PubMed

    Lin, W J; Savaiano, D A; Harlander, S K

    1989-02-01

    A method was developed for determining the specific activity of bacterial beta-galactosidase (EC 3.2.1.23) during growth of Streptococcus thermophilus and Lactobacillus bulgaricus in skim milk. Individual and mixed strain cultures of S. thermophilus (St 3642, St14485) and L. bulgaricus (Lb11842, Lb880) were examined for growth (OD at 600 nm and viable cell counts), acid production, and beta-galactosidase activity (expressed as a function of recoverable TCA-precipitable cellular protein). Cultures were inoculated into 10% skim milk (2% inoculum) and incubated at 40 degrees C for 12 h. Aliquots were removed at 2-h intervals and diluted with ice cold EDTA, pH 12. The EDTA chelates calcium and solubilizes milk protein, allowing separation of the bacteria by centrifugation. Cells were then washed twice with 20 mM phosphate buffer and disrupted by sonication. Cell debris and intact cells were removed by centrifugation and the cell-free extract evaluated for beta-galactosidase activity using o-nitrophenyl-beta-D-galactopyranoside as substrate. Specific activities ranged from 0 to 6 units/mg protein. This simple and reproducible method is applicable for enzyme assays and measurement of cellular components where contamination by milk proteins is a potential problem.

  9. Heat stability and acid gelation properties of calcium-enriched reconstituted skim milk affected by ultrasonication.

    PubMed

    Chandrapala, Jayani; Bui, Don; Kentish, Sandra; Ashokkumar, Muthupandian

    2014-05-01

    The aggregation of proteins after heating of calcium-fortified milks has been an ongoing problem in the dairy industry. This undesirable effect restricts the manufacture of calcium rich dairy products. To overcome this problem, a completely new approach in controlling the heat stability of dairy protein solutions, developed in our lab, has been employed. In this approach, high intensity, low frequency ultrasound is applied for a very short duration after a pre-heating step at ⩾70 °C. The ultrasound breaks apart whey/whey and whey/casein aggregates through the process of acoustic cavitation. Protein aggregates do not reform on subsequent post-heating, thereby making the systems heat stable. In this paper, the acid gelation properties of ultrasonicated calcium-enriched skim milks have also been investigated. It is shown that ultrasonication alone does not change the gelation properties significantly whereas a sequence of preheating (72 °C/1 min) followed by ultrasonication leads to decreased gelation times, decreased gel syneresis and increased skim milk viscosity in comparison to heating alone. Overall, ultrasonication has the potential to provide calcium-fortified dairy products with increased heat stability. However, enhanced gelation properties can only be achieved when ultrasonication is completed in conjunction with heating.

  10. Cream skimming and hospital transfers in a mixed public-private system.

    PubMed

    Cheng, Terence C; Haisken-DeNew, John P; Yong, Jongsay

    2015-05-01

    The increasing prominence of the private sector in health care provision has generated considerable interest in understanding its implications on quality and cost. This paper investigates the phenomenon of cream skimming in a mixed public-private hospital setting using the novel approach of analysing hospital transfers. We analyse hospital administrative data of patients with ischemic heart disease from the state of Victoria, Australia. The data set contains approximately 1.77 million admission episodes in 309 hospitals, of which 132 are public hospitals, and 177 private hospitals. We ask if patients transferred between public and private hospitals differ systematically in the severity and complexity of their medical conditions; and if so, whether utilisation also differs. We find that patients with higher disease severity are more likely to be transferred from private to public hospitals whereas the opposite is true for patients transferred to private hospitals. We also find that patients transferred from private to public hospitals stayed longer and cost more than private-to-private transfer patients, after controlling for patients' observed health conditions and personal characteristics. Overall, the evidence is suggestive of the presence of cream skimming in the Victorian hospital system, although we cannot conclusively rule out other mechanisms that might influence hospital transfers. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. The use of whey or skimmed milk powder in fortified blended foods for vulnerable groups.

    PubMed

    Hoppe, Camilla; Andersen, Gregers S; Jacobsen, Stine; Mølgaard, Christian; Friis, Henrik; Sangild, Per T; Michaelsen, Kim F

    2008-01-01

    Fortified blended foods (FBF), especially corn soy blend, are used as food aid for millions of people worldwide, especially malnourished individuals and vulnerable groups. There are only a few studies evaluating the effect of FBF on health outcomes, and the potential negative effect of antinutrients has not been examined. Different lines of evidence suggest that dairy proteins have beneficial effects on vulnerable groups. Here we review the evidence on the effects of adding whey or skimmed milk powder to FBF used for malnourished infants and young children or people living with HIV or AIDS. Adding whey or skimmed milk powder to FBF improves the protein quality, allowing a reduction in total amount of protein, which could have potential metabolic advantages. It also allows for a reduced content of soy and cereal and thereby a reduction of potential antinutrients. It is possible that adding milk could improve weight gain, linear growth, and recovery from malnutrition, but this needs to be confirmed. Bioactive factors in whey might have beneficial effects on the immune system and muscle synthesis, but evidence from vulnerable groups is lacking. Milk proteins will improve flavor, which is important for acceptability in vulnerable groups. The most important disadvantage is a considerable increase in price. Adding 10-15% milk powder would double the price, which means that such a product should be used only in well-defined vulnerable groups with special needs. The potential beneficial effects of adding milk protein and lack of evidence in vulnerable groups call for randomized intervention studies.

  12. Production of benzoic acid as a natural compound in fermented skim milk using commercial cheese starter.

    PubMed

    Park, Sun-Young; Yoo, Mi-Young; Paik, Hyun-Dong; Lim, Sang-Dong

    2017-06-01

    In this study, we investigated the production of natural benzoic acid (BA) in skim milk fermentation by 5 kinds of commercial cheese starters. Five kinds of starter were inoculated into 10% reconstituted skim milk, and then the culture was incubated at 2-h intervals for 10 h at 30, 35, and 40°C. In fermentation by MW 046 N+LH 13, the starter for making raclette, BA was highly detected after 8 h at 30 and 35°C. In fermentation by LH 13, the starter for making berg, BA steadily increased and was highly detected at 40°C. In fermentation by TCC-3+TCC-4, the starter for making Caciocavallo and mozzarella, BA was detected after 2 h at 40°C. Also, BA was detected after 4 and 8 h at 35 and 30°C, respectively. In fermentation by Flora-Danica, the starter for making Gouda, BA was increased until 6 h and decreased after 6 h at all temperatures. Among the 5 kinds of fermentation, the level of BA was the highest in fermentation by Flora-Danica at 6 h at 35°C, at 14.55 mg/kg. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  13. Relationship between physical properties of casein micelles and rheology of skim milk concentrate.

    PubMed

    Karlsson, A O; Ipsen, R; Schrader, K; Ardö, Y

    2005-11-01

    The properties of casein micelles in milk concentrates are of interest for the use of ultrafiltered (UF) skim milk concentrates in dairy products, and for the general understanding of colloidal stability and behavior of the casein micelle. The rheological behavior of UF skim milk concentrate with a casein concentration of 19.5% (wt/wt) was investigated at different pH and NaCl concentrations by analyzing flow viscometry and small amplitude oscillatory shear measurements. Viscometric flow curves were fitted to the Carreau-Yasuda model with the aim of determining values for the viscosity at infinite high shear rates and thereby estimate the voluminosity of the casein micelles (nu(casein)) in the UF concentrate. The voluminosity of the casein micelles increased with addition of NaCl and decreased when pH was decreased from 6.5 to 5.5. At pH 5.2, nu(casein) increased because of acid-induced aggregation of the casein micelles. The changes in nu(casein) could be interpreted from transmission electron microscopy of freeze-fractured samples of the UF concentrate and partly from dynamic light scattering measurements. Altered interactions between casein micelles due to different pH and NaCl concentrations are proposed to occur due to collapse of the kappa-casein layer, changed ionic strength, and altered distance between casein micelles.

  14. Hyb-Seq: Combining target enrichment and genome skimming for plant phylogenomics1

    PubMed Central

    Weitemier, Kevin; Straub, Shannon C. K.; Cronn, Richard C.; Fishbein, Mark; Schmickl, Roswitha; McDonnell, Angela; Liston, Aaron

    2014-01-01

    • Premise of the study: Hyb-Seq, the combination of target enrichment and genome skimming, allows simultaneous data collection for low-copy nuclear genes and high-copy genomic targets for plant systematics and evolution studies. • Methods and Results: Genome and transcriptome assemblies for milkweed (Asclepias syriaca) were used to design enrichment probes for 3385 exons from 768 genes (>1.6 Mbp) followed by Illumina sequencing of enriched libraries. Hyb-Seq of 12 individuals (10 Asclepias species and two related genera) resulted in at least partial assembly of 92.6% of exons and 99.7% of genes and an average assembly length >2 Mbp. Importantly, complete plastomes and nuclear ribosomal DNA cistrons were assembled using off-target reads. Phylogenomic analyses demonstrated signal conflict between genomes. • Conclusions: The Hyb-Seq approach enables targeted sequencing of thousands of low-copy nuclear exons and flanking regions, as well as genome skimming of high-copy repeats and organellar genomes, to efficiently produce genome-scale data sets for phylogenomics. PMID:25225629

  15. Effect of calcium on microstructure and meltability of part skim mozzarella cheese.

    PubMed

    Joshi, N S; Muthukumarappan, K; Dave, R I

    2004-07-01

    The role of calcium in the microstructure of part skim Mozzarella cheese was evaluated using scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). Part skim Mozzarella cheeses with 4 calcium levels (control 0.65%, T1 0.48%, T2, 0.42%, and T3 0.35%) were manufactured and stored at 4 degrees C. Microstructure and meltability of cheeses were studied on d 1 and 30. The micrographs were analyzed for numbers, area, perimeter, roundness, and size of the fat particles. Reduced calcium cheeses had greater meltability and more hydrated protein matrix with greater number of fat particles (control=125, T1=193, T2=184, and T3=215 with SEM and control = 86, T1=87, T2= 125, and T3= 140 with CLSM). Further, area and perimeter of these fat particles were also greater in reduced calcium cheeses. Area, perimeter, and size of fat particles increased and their roundness decreased upon storage of 30 d. Decrease in free serum in the protein matrix of all cheeses upon refrigerated storage was evident from the CLSM. Hydrated protein network and better emulsified fat in low calcium cheeses might have improved melt properties of Mozzarella cheese.

  16. Effect of soluble calcium and lactose on limiting flux and serum protein removal during skim milk microfiltration.

    PubMed

    Adams, Michael C; Hurt, Emily E; Barbano, David M

    2015-11-01

    The tendency of calcium to promote microfiltration (MF) membrane fouling is well documented, but the role of lactose has not been studied. Milk protein concentrate that is 85% protein on a dry basis (MPC85) contains less calcium and lactose than skim milk. Our objectives were to determine the effects of skim milk soluble calcium and lactose concentrations on the limiting fluxes (LF) and serum protein (SP) removal factors of 0.1-µm ceramic graded permeability membranes. The MF was fed with 3 different milks: skim milk, liquid MPC85 that had been standardized to the protein content of skim milk with reverse osmosis water (MPC), and liquid MPC85 that had been standardized to the protein and lactose contents of skim milk with reverse osmosis water and lactose monohydrate (MPC+L). Retentate and permeate were continuously recycled to the feed tank. The LF for each feed was determined by increasing flux once per hour from 55 kg·m(-2)·h(-1) until flux did not increase with increasing transmembrane pressure. Temperature, pressure drop across the membrane length, and protein concentration in the retentate recirculation loop were maintained at 50°C, 220 kPa, and 8.77 ± 0.2%, respectively. Experiments were replicated 3 times and the Proc GLM procedure of SAS was used for statistical analysis. An increase in LF between skim milk (91 kg·m(-2)·h(-1)) and MPC+L (124 kg·m(-2)·h(-1)) was associated with a reduction in soluble calcium. The LF of MPC+L was lower than the LF of MPC (137 kg·m(-2)·h(-1)) due to the higher viscosity contributed by lactose. Permeates produced from the MPC and MPC+L contained more protein than the skim milk permeate due to the transfer of caseins from the micelles into the reduced-calcium sera of the MPC and MPC+L. A SP removal factor was calculated by dividing true protein in the permeate by SP in the permeate portion of the feed to describe the ease of SP passage through the membrane. No differences in SP removal factors were detected among the

  17. Molecular insights into the reversible formation of tau protein fibrils.

    PubMed

    Luo, Yin; Dinkel, Paul; Yu, Xiang; Margittai, Martin; Zheng, Jie; Nussinov, Ruth; Wei, Guanghong; Ma, Buyong

    2013-05-04

    We computationally and experimentally showed that tau protein fibrils can be formed at high temperature. When cooled, the fibrils dissociate back to monomers. Heparin promotes tau fibril formation and prevents its reversion. Our results revealed the physicochemical mechanism of reversible formation of tau fibrils.

  18. Recent Results From BaBar in Tau Physics

    SciTech Connect

    Lewczuk, Mateusz; /Victoria U.

    2009-06-25

    The BaBar collaboration has accumulated over 400 million {tau}-pairs which can be used to study charged leptonic and hadronic weak currents to unprecedented precision. This note presents results on lepton universality, measurements of |V{sub us}|, and searches for {tau} decays which violate lepton flavour conservation, or {tau} decays that proceed through a suppressed second class current.

  19. Antisense Reduction of Tau in Adult Mice Protects against Seizures

    PubMed Central

    DeVos, Sarah L.; Goncharoff, Dustin K.; Chen, Guo; Kebodeaux, Carey S.; Yamada, Kaoru; Stewart, Floy R.; Schuler, Dorothy R.; Maloney, Susan E.; Wozniak, David F.; Rigo, Frank; Bennett, C. Frank; Cirrito, John R.; Holtzman, David M.

    2013-01-01

    Tau, a microtubule-associated protein, is implicated in the pathogenesis of Alzheimer's Disease (AD) in regard to both neurofibrillary tangle formation and neuronal network hyperexcitability. The genetic ablation of tau substantially reduces hyperexcitability in AD mouse lines, induced seizure models, and genetic in vivo models of epilepsy. These data demonstrate that tau is an important regulator of network excitability. However, developmental compensation in the genetic tau knock-out line may account for the protective effect against seizures. To test the efficacy of a tau reducing therapy for disorders with a detrimental hyperexcitability profile in adult animals, we identified antisense oligonucleotides that selectively decrease endogenous tau expression throughout the entire mouse CNS—brain and spinal cord tissue, interstitial fluid, and CSF—while having no effect on baseline motor or cognitive behavior. In two chemically induced seizure models, mice with reduced tau protein had less severe seizures than control mice. Total tau protein levels and seizure severity were highly correlated, such that those mice with the most severe seizures also had the highest levels of tau. Our results demonstrate that endogenous tau is integral for regulating neuronal hyperexcitability in adult animals and suggest that an antisense oligonucleotide reduction of tau could benefit those with epilepsy and perhaps other disorders associated with tau-mediated neuronal hyperexcitability. PMID:23904623

  20. Estimation of Tau and Phosphorylated Tau181 in Serum of Alzheimer’s Disease and Mild Cognitive Impairment Patients

    PubMed Central

    Shekhar, Shashank; Kumar, Rahul; Rai, Nitish; Kumar, Vijay; Singh, Kusum; Upadhyay, Ashish Datt; Tripathi, Manjari; Dwivedi, Sadanand; Dey, Aparajit B.; Dey, Sharmistha

    2016-01-01

    The elevated level of cerebrospinal fluid (CSF) Tau and phosphorylated Tau181 (p-Tau181) proteins are well established hallmarks of Alzheimer’s disease (AD). Elevated level of p-Tau181 can differentiate AD from other neurodegenerative disease. However, the expression level of these proteins in serum of AD patient is not well set up. This study sought to evaluate the level of Tau and p-Tau181 in serum of AD, and mild cognitive impairment (MCI) patients for an alternative approach to establish protein-based markers by convenient way. Blood samples were collected from 39 AD patients, 37 MCI patients and 37 elderly individuals as controls. The levels of Tau and p-Tau181 in the serum of the different groups were measured by label free real time Surface Plasmon Resonance technology by using specific antibodies, and were further confirmed by the conventional western blot method. An appropriate statistical analysis, including Receiver Operating Characteristic (ROC), was performed. The concentrations of serum Tau and p-Tau181 were significantly higher (p<0.00001) in AD (Tau; 47.49±9.00ng/μL, p-Tau181; 0.161±0.04 ng/μL) compared to MCI (Tau; 39.26±7.78 ng/μL, p-Tau181; 0.135±0.02 ng/μL) and were further higher compared to elderly controls (Tau; 34.92±6.58 ng/μL, p-Tau181; 0.122±0.01 ng/ μL). A significant (p<0.0001) downhill correlation was found between Tau as well as p-Tau181 levels with HMSE and MoCA score. This study for the first time reports the concentration of Tau and p-Tau181 in serum of AD and MCI patients. The cutoff values of Tau and p-Tau181 of AD and MCI patients with sensitivity and specificity reveal that serum level of these proteins can be used as a predictive marker for AD and MCI. PMID:27459603

  1. Tau-tubulin kinase 1 enhances prefibrillar tau aggregation and motor neuron degeneration in P301L FTDP-17 tau-mutant mice.

    PubMed

    Xu, Jiqing; Sato, Shinji; Okuyama, Satoshi; Swan, Russell J; Jacobsen, Michael T; Strunk, Elena; Ikezu, Tsuneya

    2010-08-01

    Tau-tubulin kinase-1 (TTBK1) phosphorylates microtubule-associated protein tau at specific serine/threonine residues found in paired helical filaments (PHFs), and its expression is up-regulated in the brain in Alzheimer disease, suggesting its role in tauopathy pathogenesis. To understand the effects of TTBK1 on tauopathy in vivo, we have developed bigenic mice overexpressing full-length TTBK1 and the P301L tau mutant. The bigenic mice show enhanced tau phosphorylation at multiple sites (AT8, 12E8, PHF-1, and pS422), tauC3-immunoreactive tau fragmentation, and accumulation of tau aggregates in cortical and hippocampal neurons at 12-13 mo of age. However, the phosphorylated tau aggregates were predominantly sarkosyl soluble and migrated in the light sucrose density fraction after discontinuous sucrose gradient ultracentrifugation, which suggests that they form small oligomers. The bigenic mice show significant locomotor dysfunction as determined by both rotorod and grip strength tests, as well as enhanced loss of motor neurons in the L4-L5 spinal cord. This neuronal dysfunction and degeneration was associated with increased levels of tau oligomers, cyclin-dependent protein kinase 5 activators p35 and p25, and pY216 phosphorylated glycogen synthase kinase 3-beta. These data suggest that TTBK1 up-regulation enhances tau phosphorylation and oligomerization, whose toxicity results in enhanced neurodegeneration and locomotor dysfunction in a tauopathy animal model.

  2. Tau identification using multivariate techniques in ATLAS

    NASA Astrophysics Data System (ADS)

    O'Neil, D. C.; ATLAS Collaboration

    2012-06-01

    Tau leptons play an important role in the physics program of the LHC. They are being used in electroweak measurements, in detector related studies and in searches for new phenomena like the Higgs boson or Supersymmetry. In the detector, tau leptons are reconstructed as collimated jets with low track multiplicity. Due to the background from QCD multijet processes, efficient tau identification techniques with large fake rejection are essential. Since single variable criteria are not enough to efficiently separate them from jets and electrons, modern multivariate techniques are used. In ATLAS, several advanced algorithms are applied to identify taus, including a projective likelihood estimator and boosted decision trees. All multivariate methods applied to the ATLAS simulated data perform better than the baseline cut analysis. Their performance is shown using high energy data collected at the ATLAS experiment. The improvement ranges from a factor of 2 to 5 in rejection for the same efficiency, depending on the selected efficiency operating point and the number of prongs in the tau decay. The strengths and weaknesses of each technique are also discussed.

  3. Proline Conformation in a Functional Tau Fragment.

    PubMed

    Ahuja, Puneet; Cantrelle, François-Xavier; Huvent, Isabelle; Hanoulle, Xavier; Lopez, Juan; Smet, Caroline; Wieruszeski, Jean-Michel; Landrieu, Isabelle; Lippens, G

    2016-01-16

    The conformational state of distinct prolines can determine the folding of a protein but equally other biological processes when coupled to a conformation-sensitive secondary reaction. For the neuronal tau protein, the importance of proline conformation is underscored by its interaction with different prolyl cis/trans isomerases. The proline conformation would gain even further importance after phosphorylation of the preceding residue by various proline-directed kinases. A number of molecular diseases including Alzheimer's disease and traumatic brain injury were thereby recently qualified as "cistauosis", as they would imply a cis conformation for the pThr231-Pro232 prolyl bond. We here investigate by NMR spectroscopy the conformation of all prolines in a functional Tau fragment, Tau[208-324]. Although we can detect and identify some minor conformers in the cis form, we show that all prolines are for over 90% in the trans conformation. Phosphorylation by CDK2/CycA3, which notably leads to complete modification of the Thr231 residue, does not change this conclusion. Our data hence disagree with the notion that specific prolyl bonds in tau would adopt preferentially the cis conformation.

  4. Determination of the Michel parameters and the {tau} neutrino helicity in {tau} decay

    SciTech Connect

    CLEO Collaboration

    1997-11-01

    Using the CLEO II detector at the Cornell Electron Storage Ring operated at {radical} (s) =10.6GeV, we have determined the Michel parameters {rho}, {xi}, and {delta} in {tau}{sup {minus_plus}}{r_arrow}l{sup {minus_plus}}{nu}{bar {nu}} decay as well as the {tau} neutrino helicity parameter h{sub {nu}{sub {tau}}} in {tau}{sup {minus_plus}}{r_arrow}{pi}{sup {minus_plus}}{pi}{sup 0}{nu} decay. From a data sample of 3.02{times}10{sup 6} produced {tau} pairs we analyzed events of the topologies e{sup +}e{sup {minus}}{r_arrow}{tau}{sup +}{tau}{sup {minus}}{r_arrow}(l{sup {plus_minus}}{nu}{bar {nu}})({pi}{sup {minus_plus}}{pi}{sup 0}{nu}) and e{sup +}e{sup {minus}}{r_arrow}{tau}{sup +}{tau}{sup {minus}}{r_arrow}({pi}{sup {plus_minus}}{pi}{sup 0}{bar {nu}})({pi}{sup {minus_plus}}{pi}{sup 0}{nu}). We obtain {rho}=0.747{rho}=0.747{plus_minus}0.010{plus_minus}0.006, {xi}=1.007{plus_minus}0.040{plus_minus}0.015, {xi}{delta}=0.745{plus_minus}0.026{plus_minus}0.009, and h{sub {nu}{sub {tau}}}={minus}0.995{plus_minus}0.010{plus_minus}0.003, where we have used the previously determined sign of h{sub {nu}{sub {tau}}} [ARGUS Collaboration, H. Albrecht {ital et al.}, Z. Phys. C {bold 58}, 61 (1993); Phys. Lett. B {bold 349}, 576 (1995)]. We also present the Michel parameters as determined from the electron and muon samples separately. All results are in agreement with the standard model V{minus}A interaction. {copyright} {ital 1997} {ital The American Physical Society}

  5. Loss of Axonal Mitochondria Promotes Tau-Mediated Neurodegeneration and Alzheimer's Disease–Related Tau Phosphorylation Via PAR-1

    PubMed Central

    Iijima-Ando, Kanae; Sekiya, Michiko; Suzuki, Emiko; Lu, Bingwei; Iijima, Koichi M.

    2012-01-01

    Abnormal phosphorylation and toxicity of a microtubule-associated protein tau are involved in the pathogenesis of Alzheimer's disease (AD); however, what pathological conditions trigger tau abnormality in AD is not fully understood. A reduction in the number of mitochondria in the axon has been implicated in AD. In this study, we investigated whether and how loss of axonal mitochondria promotes tau phosphorylation and toxicity in vivo. Using transgenic Drosophila expressing human tau, we found that RNAi–mediated knockdown of milton or Miro, an adaptor protein essential for axonal transport of mitochondria, enhanced human tau-induced neurodegeneration. Tau phosphorylation at an AD–related site Ser262 increased with knockdown of milton or Miro; and partitioning defective-1 (PAR-1), the Drosophila homolog of mammalian microtubule affinity-regulating kinase, mediated this increase of tau phosphorylation. Tau phosphorylation at Ser262 has been reported to promote tau detachment from microtubules, and we found that the levels of microtubule-unbound free tau increased by milton knockdown. Blocking tau phosphorylation at Ser262 site by PAR-1 knockdown or by mutating the Ser262 site to unphosphorylatable alanine suppressed the enhancement of tau-induced neurodegeneration caused by milton knockdown. Furthermore, knockdown of milton or Miro increased the levels of active PAR-1. These results suggest that an increase in tau phosphorylation at Ser262 through PAR-1 contributes to tau-mediated neurodegeneration under a pathological condition in which axonal mitochondria is depleted. Intriguingly, we found that knockdown of milton or Miro alone caused late-onset neurodegeneration in the fly brain, and this neurodegeneration could be suppressed by knockdown of Drosophila tau or PAR-1. Our results suggest that loss of axonal mitochondria may play an important role in tau phosphorylation and toxicity in the pathogenesis of AD. PMID:22952452

  6. Extensive p-tau pathology and SDS-stable p-tau oligomers in Alzheimer’s cortical synapses

    PubMed Central

    Henkins, Kristen M.; Sokolow, Sophie; Miller, Carol A.; Vinters, Harry V.; Poon, Wayne; Cornwell, Lindsey B.; Saing, Tommy; Gylys, Karen Hoppens

    2012-01-01

    Like amyloid beta (Aβ) oligomers, tau aggregates are increasingly recognized as potential key toxic intermediates in Alzheimer’s disease and as therapeutic targets. P-tau co-localizes with Aβ in cortical AD synapses and may contribute to synapse dysfunction and loss. Flow cytometry analysis of synaptosomes from AD compared to aged cognitively normal cortex demonstrates increased immunolabeling for three p-tau antibodies (AT8, PHF-1 and pS422), indicating phosphorylation at multiple tau epitopes. Sequential extraction experiments show increased soluble p-tau in AD synapses, but a sizable pool of p-tau requires detergent solubilization, suggesting endosomal/lysosomal localization. P-tau is co-localized with Aβ in individual synaptosomes in dual labeling experiments, and flow cytometry sorting of Aβ-positive synaptosomes from an AD case reveals a marked enrichment of p-tau aggregates. The p-tau enrichment, a 76-fold increase over the initial homogenate, is consistent with sequestration of p-tau in internal synaptic compartments. Western analysis of a series of AD and normal cases shows SDS-stable tau oligomers in the dimer/trimer size range in AD samples. These results indicate that widespread synaptic p-tau pathology accompanies Aβ accumulations in surviving synaptic terminals, particularly in late-stage AD. PMID:22486774

  7. Extensive p-tau pathology and SDS-stable p-tau oligomers in Alzheimer's cortical synapses.

    PubMed

    Henkins, Kristen M; Sokolow, Sophie; Miller, Carol A; Vinters, Harry V; Poon, Wayne W; Cornwell, Lindsey B; Saing, Tommy; Gylys, Karen Hoppens

    2012-11-01

    Like amyloid beta (Aβ) oligomers, tau aggregates are increasingly recognized as potential key toxic intermediates in Alzheimer's disease (AD) and as therapeutic targets. P-tau co-localizes with Aβ in cortical AD synapses and may contribute to synapse dysfunction and loss. Flow cytometry analysis of synaptosomes from AD compared with aged cognitively normal cortex demonstrates increased immunolabeling for three p-tau antibodies (AT8, PHF-1 and pS422), indicating phosphorylation at multiple tau epitopes. Sequential extraction experiments show increased soluble p-tau in AD synapses, but a sizable pool of p-tau requires detergent solubilization, suggesting endosomal/lysosomal localization. P-tau is co-localized with Aβ in individual synaptosomes in dual labeling experiments, and flow cytometry sorting of Aβ-positive synaptosomes from an AD case reveals a marked enrichment of p-tau aggregates. The p-tau enrichment, a 76-fold increase over the initial homogenate, is consistent with sequestration of p-tau in internal synaptic compartments. Western analysis of a series of AD and normal cases shows SDS-stable tau oligomers in the dimer/trimer size range in AD samples. These results indicate that widespread synaptic p-tau pathology accompanies Aβ accumulations in surviving synaptic terminals, particularly in late-stage AD.

  8. Escitalopram Ameliorates Forskolin-Induced Tau Hyperphosphorylation in HEK239/tau441 Cells.

    PubMed

    Ren, Qing-Guo; Wang, Yan-Juan; Gong, Wei-Gang; Zhou, Qi-Da; Xu, Lin; Zhang, Zhi-Jun

    2015-06-01

    To investigate the effect of escitalopram (a widely used and highly efficacious antidepressant from the SSRI class) on tau hyperphosphorylation, HEK293/tau441 cells were pretreated with 4 μM of forskolin for 2 h. Then we treated the cells with different doses of escitalopram (0, 5, 10, 20, 40, 80 μM) for 22 h. We measured the phosphorylation level of tau by Western blotting. It was shown that escitalopram could protect tau from hyperphosphorylation induced by pharmacological activation of protein kinase A (PKA) at a dose of 20, 40, and 80 μM in vitro. Interestingly, the same dose of escitalopram could also increase the level of serine-9-phosphorylated GSK-3β (inactive form) and the phosphorylation level of Akt at Ser473 (active form) with no significant change in the level of total GSK-3β and Akt. Unexpectedly, 5-hydroxytryptamine 1A receptor (5-HT1A) agonist 8-OH-DPAT did not decrease forskolin-induced tau hyperphosphorylation. Our results suggest that escitalopram can ameliorate forskolin-induced tau hyperphosphorylation, which is not through the typical 5-HT1A pathway, and Akt/GSK-3β signaling pathway is involved. These findings may support an effective role of antidepressants in the prevention of dementia associated with depression in patients.

  9. Resolved multifrequency radio observations of GG Tau

    SciTech Connect

    Andrews, Sean M.; Birnstiel, T.; Rosenfeld, K. A.; Wilner, D. J.; Chandler, Claire J.; Pérez, L. M.; Isella, Andrea; Ricci, L.; Carpenter, J. M.; Calvet, N.; Corder, S. A.; Deller, A. T.; Dullemond, C. P.; Greaves, J. S.; Harris, R. J.; Henning, Th.; Linz, H.; Kwon, W.; Lazio, J.; Mundy, L. G.; and others

    2014-06-01

    We present subarcsecond resolution observations of continuum emission associated with the GG Tau quadruple star system at wavelengths of 1.3, 2.8, 7.3, and 50 mm. These data confirm that the GG Tau A binary is encircled by a circumbinary ring at a radius of 235 AU with a FWHM width of ∼60 AU. We find no clear evidence for a radial gradient in the spectral shape of the ring, suggesting that the particle size distribution is spatially homogeneous on angular scales ≳0.''1. A central point source, likely associated with the primary component (GG Tau Aa), exhibits a composite spectrum from dust and free-free emission. Faint emission at 7.3 mm is observed toward the low-mass star GG Tau Ba, although its origin remains uncertain. Using these measurements of the resolved, multifrequency emission structure of the GG Tau A system, models of the far-infrared to radio spectrum are developed to place constraints on the grain size distribution and dust mass in the circumbinary ring. The non-negligible curvature present in the ring spectrum implies a maximum particle size of 1-10 mm, although we are unable to place strong constraints on the distribution shape. The corresponding dust mass is 30-300 M {sub ⊕}, at a temperature of 20-30 K. We discuss how this significant concentration of relatively large particles in a narrow ring at a large radius might be produced in a local region of higher gas pressures (i.e., a particle 'trap') located near the inner edge of the circumbinary disk.

  10. Caspase-Cleaved Tau Impairs Mitochondrial Dynamics in Alzheimer's Disease.

    PubMed

    Pérez, María José; Vergara-Pulgar, Katiana; Jara, Claudia; Cabezas-Opazo, Fabian; Quintanilla, Rodrigo A

    2017-01-13

    Alzheimer's disease (AD) is characterized by the presence of aggregates of tau protein. Tau truncated by caspase-3 (D421) or tau hyperphosphorylated at Ser396/S404 might play a role in the pathogenesis of AD. Mitochondria are dynamic organelles that modify their size and function through mitochondrial dynamics. Recent studies have shown that alterations of mitochondrial dynamics affect synaptic communication. Therefore, we studied the effects of pathological forms of tau on the regulation of mitochondrial dynamics. We used primary cortical neurons from tau(-/-) knockout mice and immortalized cortical neurons (CN1.4) that were transfected with plasmids containing green fluorescent protein (GFP) or GFP with different tau forms: full-length (GFP-T4), truncated (GFP-T4C3), pseudophosphorylated (GFP-T42EC), or both truncated and pseudophosphorylated modifications of tau (GFP-T4C3-2EC). Cells expressing truncated tau showed fragmented mitochondria compared to cells that expressed full-length tau. These findings were corroborated using primary neurons from tau(-/-) knockout mice that expressed the truncated and both truncated and pseudophosphorylated forms of tau. Interestingly, mitochondrial fragmentation was accompanied by a significant reduction in levels of optic atrophy protein 1 (Opa1) in cells expressing the truncated form of tau. In addition, treatment with low concentrations of amyloid-beta (Aβ) significantly reduced mitochondrial membrane potential, cell viability, and mitochondrial length in cortical cells and primary neurons from tau(-/-) mice that express truncated tau. These results indicate that the presence of tau pathology impairs mitochondrial dynamics by reducing Opa1 levels, an event that could lead to mitochondrial impairment observed in AD.

  11. Trans-cellular propagation of Tau aggregation by fibrillar species.

    PubMed

    Kfoury, Najla; Holmes, Brandon B; Jiang, Hong; Holtzman, David M; Diamond, Marc I

    2012-06-01

    Aggregation of the microtubule associated protein Tau is associated with several neurodegenerative disorders, including Alzheimer disease and frontotemporal dementia. In Alzheimer disease, Tau pathology spreads progressively throughout the brain, possibly along existing neural networks. However, it is still unclear how the propagation of Tau misfolding occurs. Intriguingly, in animal models, vaccine-based therapies have reduced Tau and synuclein pathology by uncertain mechanisms, given that these proteins are intracellular. We have previously speculated that trans-cellular propagation of misfolding could be mediated by a process similar to prion pathogenesis, in which fibrillar Tau aggregates spread pathology from cell to cell. However, there has been little evidence to demonstrate true trans-cellular propagation of Tau misfolding, in which Tau aggregates from one cell directly contact Tau protein in the recipient cell to trigger further aggregation. Here we have observed that intracellular Tau fibrils are directly released into the medium and then taken up by co-cultured cells. Internalized Tau aggregates induce fibrillization of intracellular Tau in these naive recipient cells via direct protein-protein contact that we demonstrate using FRET. Tau aggregation can be amplified across several generations of cells. An anti-Tau monoclonal antibody blocks Tau aggregate propagation by trapping fibrils in the extracellular space and preventing their uptake. Thus, propagation of Tau protein misfolding among cells can be mediated by release and subsequent uptake of fibrils that directly contact native protein in recipient cells. These results support the model of aggregate propagation by templated conformational change and suggest a mechanism for vaccine-based therapies in neurodegenerative diseases.

  12. Trans-cellular Propagation of Tau Aggregation by Fibrillar Species*

    PubMed Central

    Kfoury, Najla; Holmes, Brandon B.; Jiang, Hong; Holtzman, David M.; Diamond, Marc I.

    2012-01-01

    Aggregation of the microtubule associated protein Tau is associated with several neurodegenerative disorders, including Alzheimer disease and frontotemporal dementia. In Alzheimer disease, Tau pathology spreads progressively throughout the brain, possibly along existing neural networks. However, it is still unclear how the propagation of Tau misfolding occurs. Intriguingly, in animal models, vaccine-based therapies have reduced Tau and synuclein pathology by uncertain mechanisms, given that these proteins are intracellular. We have previously speculated that trans-cellular propagation of misfolding could be mediated by a process similar to prion pathogenesis, in which fibrillar Tau aggregates spread pathology from cell to cell. However, there has been little evidence to demonstrate true trans-cellular propagation of Tau misfolding, in which Tau aggregates from one cell directly contact Tau protein in the recipient cell to trigger further aggregation. Here we have observed that intracellular Tau fibrils are directly released into the medium and then taken up by co-cultured cells. Internalized Tau aggregates induce fibrillization of intracellular Tau in these naive recipient cells via direct protein-protein contact that we demonstrate using FRET. Tau aggregation can be amplified across several generations of cells. An anti-Tau monoclonal antibody blocks Tau aggregate propagation by trapping fibrils in the extracellular space and preventing their uptake. Thus, propagation of Tau protein misfolding among cells can be mediated by release and subsequent uptake of fibrils that directly contact native protein in recipient cells. These results support the model of aggregate propagation by templated conformational change and suggest a mechanism for vaccine-based therapies in neurodegenerative diseases. PMID:22461630

  13. Search for a low-mass higgs boson in Upsilon(3S)-->gammaA(0), A(0)-->tau(+)tau(-) at BABAR.

    PubMed

    Aubert, B; Karyotakis, Y; Lees, J P; Poireau, V; Prencipe, E; Prudent, X; Tisserand, V; Tico, J Garra; Grauges, E; Martinelli, M; Palano, A; Pappagallo, M; Eigen, G; Stugu, B; Sun, L; Battaglia, M; Brown, D N; Kerth, L T; Kolomensky, Yu G; Lynch, G; Osipenkov, I L; Tackmann, K; Tanabe, T; Hawkes, C M; Soni, N; Watson, A T; Koch, H; Schroeder, T; Asgeirsson, D J; Fulsom, B G; Hearty, C; Mattison, T S; McKenna, J A; Barrett, M; Khan, A; Randle-Conde, A; Blinov, V E; Bukin, A D; Buzykaev, A R; Druzhinin, V P; Golubev, V B; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Todyshev, K Yu; Bondioli, M; Curry, S; Eschrich, I; Kirkby, D; Lankford, A J; Lund, P; Mandelkern, M; Martin, E C; Stoker, D P; Atmacan, H; Gary, J W; Liu, F; Long, O; Vitug, G M; Yasin, Z; Sharma, V; Campagnari, C; Hong, T M; Kovalskyi, D; Mazur, M A; Richman, J D; Beck, T W; Eisner, A M; Heusch, C A; Kroseberg, J; Lockman, W S; Martinez, A J; Schalk, T; Schumm, B A; Seiden, A; Wang, L; Winstrom, L O; Cheng, C H; Doll, D A; Echenard, B; Fang, F; Hitlin, D G; Narsky, I; Ongmongkolkul, P; Piatenko, T; Porter, F C; Andreassen, R; Mancinelli, G; Meadows, B T; Mishra, K; Sokoloff, M D; Bloom, P C; Ford, W T; Gaz, A; Hirschauer, J F; Nagel, M; Nauenberg, U; Smith, J G; Wagner, S R; Ayad, R; Toki, W H; Wilson, R J; Feltresi, E; Hauke, A; Jasper, H; Karbach, T M; Merkel, J; Petzold, A; Spaan, B; Wacker, K; Kobel, M J; Nogowski, R; Schubert, K R; Schwierz, R; Bernard, D; Latour, E; Verderi, M; Clark, P J; Playfer, S; Watson, J E; Andreotti, M; Bettoni, D; Bozzi, C; Calabrese, R; Cecchi, A; Cibinetto, G; Fioravanti, E; Franchini, P; Luppi, E; Munerato, M; Negrini, M; Petrella, A; Piemontese, L; Santoro, V; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Finocchiaro, G; Pacetti, S; Patteri, P; Peruzzi, I M; Piccolo, M; Rama, M; Zallo, A; Contri, R; Guido, E; Lo Vetere, M; Monge, M R; Passaggio, S; Patrignani, C; Robutti, E; Tosi, S; Chaisanguanthum, K S; Morii, M; Adametz, A; Marks, J; Schenk, S; Uwer, U; Bernlochner, F U; Klose, V; Lacker, H M; Lueck, T; Volk, A; Bard, D J; Dauncey, P D; Tibbetts, M; Behera, P K; Charles, M J; Mallik, U; Cochran, J; Crawley, H B; Dong, L; Eyges, V; Meyer, W T; Prell, S; Rosenberg, E I; Rubin, A E; Gao, Y Y; Gritsan, A V; Guo, Z J; Arnaud, N; Béquilleux, J; D'Orazio, A; Davier, M; Derkach, D; da Costa, J Firmino; Grosdidier, G; Le Diberder, F; Lepeltier, V; Lutz, A M; Malaescu, B; Pruvot, S; Roudeau, P; Schune, M H; Serrano, J; Sordini, V; Stocchi, A; Wormser, G; Lange, D J; Wright, D M; Bingham, I; Burke, J P; Chavez, C A; Fry, J R; Gabathuler, E; Gamet, R; Hutchcroft, D E; Payne, D J; Touramanis, C; Bevan, A J; Clarke, C K; Di Lodovico, F; Sacco, R; Sigamani, M; Cowan, G; Paramesvaran, S; Wren, A C; Brown, D N; Davis, C L; Denig, A G; Fritsch, M; Gradl, W; Hafner, A; Alwyn, K E; Bailey, D; Barlow, R J; Jackson, G; Lafferty, G D; West, T J; Yi, J I; Anderson, J; Chen, C; Jawahery, A; Roberts, D A; Simi, G; Tuggle, J M; Dallapiccola, C; Salvati, E; Cowan, R; Dujmic, D; Fisher, P H; Henderson, S W; Sciolla, G; Spitznagel, M; Yamamoto, R K; Zhao, M; Patel, P M; Robertson, S H; Schram, M; Biassoni, P; Lazzaro, A; Lombardo, V; Palombo, F; Stracka, S; Cremaldi, L; Godang, R; Kroeger, R; Sonnek, P; Summers, D J; Zhao, H W; Simard, M; Taras, P; Nicholson, H; De Nardo, G; Lista, L; Monorchio, D; Onorato, G; Sciacca, C; Raven, G; Snoek, H L; Jessop, C P; Knoepfel, K J; Losecco, J M; Wang, W F; Corwin, L A; Honscheid, K; Kagan, H; Kass, R; Morris, J P; Rahimi, A M; Sekula, S J; Wong, Q K; Blount, N L; Brau, J; Frey, R; Igonkina, O; Kolb, J A; Lu, M; Rahmat, R; Sinev, N B; Strom, D; Strube, J; Torrence, E; Castelli, G; Gagliardi, N; Margoni, M; Morandin, M; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Voci, C; Del Amo Sanchez, P; Ben-Haim, E; Bonneaud, G R; Briand, H; Chauveau, J; Hamon, O; Leruste, Ph; Marchiori, G; Ocariz, J; Perez, A; Prendki, J; Sitt, S; Gladney, L; Biasini, M; Manoni, E; Angelini, C; Batignani, G; Bettarini, S; Calderini, G; Carpinelli, M; Cervelli, A; Forti, F; Giorgi, M A; Lusiani, A; Morganti, M; Neri, N; Paoloni, E; Rizzo, G; Walsh, J J; Lopes Pegna, D; Lu, C; Olsen, J; Smith, A J S; Telnov, A V; Anulli, F; Baracchini, E; Cavoto, G; Faccini, R; Ferrarotto, F; Ferroni, F; Gaspero, M; Jackson, P D; Gioi, L Li; Mazzoni, M A; Morganti, S; Piredda, G; Renga, F; Voena, C; Ebert, M; Hartmann, T; Schröder, H; Waldi, R; Adye, T; Franek, B; Olaiya, E O; Wilson, F F; Emery, S; Esteve, L; Hamel de Monchenault, G; Kozanecki, W; Vasseur, G; Yèche, Ch; Zito, M; Allen, M T; Aston, D; Bartoldus, R; Benitez, J F; Cenci, R; Coleman, J P; Convery, M R; Dingfelder, J C; Dorfan, J; Dubois-Felsmann, G P; Dunwoodie, W; Field, R C; Sevilla, M Franco; Gabareen, A M; Graham, M T; Grenier, P; Hast, C; Innes, W R; Kaminski, J; Kelsey, M H; Kim, H; Kim, P; Kocian, M L; Leith, D W G S; Li, S; Lindquist, B; Luitz, S; Luth, V; Lynch, H L; Macfarlane, D B; Marsiske, H; Messner, R; Muller, D R; Neal, H; Nelson, S; O'Grady, C P; Ofte, I; Perl, M; Ratcliff, B N; Roodman, A; Salnikov, A A; Schindler, R H; Schwiening, J; Snyder, A; Su, D; Sullivan, M K; Suzuki, K; Swain, S K; Thompson, J M; Va'vra, J; Wagner, A P; Weaver, M; West, C A; Wisniewski, W J; Wittgen, M; Wright, D H; Wulsin, H W; Yarritu, A K; Young, C C; Ziegler, V; Chen, X R; Liu, H; Park, W; Purohit, M V; White, R M; Wilson, J R; Bellis, M; Burchat, P R; Edwards, A J; Miyashita, T S; Ahmed, S; Alam, M S; Ernst, J A; Pan, B; Saeed, M A; Zain, S B; Soffer, A; Spanier, S M; Wogsland, B J; Eckmann, R; Ritchie, J L; Ruland, A M; Schilling, C J; Schwitters, R F; Wray, B C; Drummond, B W; Izen, J M; Lou, X C; Bianchi, F; Gamba, D; Pelliccioni, M; Bomben, M; Bosisio, L; Cartaro, C; Della Ricca, G; Lanceri, L; Vitale, L; Azzolini, V; Lopez-March, N; Martinez-Vidal, F; Milanes, D A; Oyanguren, A; Albert, J; Banerjee, Sw; Bhuyan, B; Choi, H H F; Hamano, K; King, G J; Kowalewski, R; Lewczuk, M J; Nugent, I M; Roney, J M; Sobie, R J; Gershon, T J; Harrison, P F; Ilic, J; Latham, T E; Mohanty, G B; Puccio, E M T; Band, H R; Chen, X; Dasu, S; Flood, K T; Pan, Y; Prepost, R; Vuosalo, C O; Wu, S L

    2009-10-30

    We search for a light Higgs boson A0 in the radiative decay Upsilon(3S)-->gammaA(0), A(0)-->tau+tau-, tau+-->e+nu(e)nu(tau), or tau+-->mu+nu(mu)nu(tau). The data sample contains 122x10(6) Upsilon(3S) events recorded with the BABAR detector. We find no evidence for a narrow structure in the studied tau+tau- invariant mass region of 4.03tau+tau-)<10.10 GeV/c2. We exclude at the 90% confidence level (C.L.) a low-mass Higgs boson decaying to tau+tau- with a product branching fraction B(Upsilon(3S)-->gammaA(0))xB(A(0)-->tau+tau-)>(1.5-16)x10(-5) across the m(tau+tau-) range. We also set a 90% C.L. upper limit on the tau+tau- decay of the eta(b) at B(eta(b)-->tau+tau-)<8%.

  14. Review of recent results on the /tau/ lepton

    SciTech Connect

    Gan, K.K.

    1988-04-01

    This is a review of the recent results on the /tau/ lepton. The results include precise measurements of the lifetime, measurements of the decay /tau//sup /minus// ..-->.. ..pi../sup /minus//2..pi../sup 0/..nu../sub /tau// with much improved precision, limits on decay modes containing /eta/ mesons, including the second-class-current decay /tau//sup /minus// ..-->.. ..pi../sup /minus///eta/..nu../sub /tau//, and limits on exotic decay modes. The implications of these results on the discrepancy in the one-charged-particle decay modes are discussed. 43 refs., 4 figs., 2 tabs.

  15. Tau Lepton Physics: Proceedings of the Second Workshop

    NASA Astrophysics Data System (ADS)

    Gan, K. K.

    The Table of Contents for the book is as follows: * International Advisory Committee and Local Organization Committee * Forward * Workshop Agenda * New Measurements of the τ Lepton Mass * Status of the Tau Lepton — View from the PDG * TAUOLA Monte Carlo for τ Decays. A Question of Systematic Errors * A Review of the τ Lifetime * A Recent CLEO II Measurement of the Branching Ratio Be(τ → eνν) * Tau Leptonic Branching Ratios with the L3 Detector * Measurements of BR( {τ \\to ev\\bar v } ) and BR( {τ \\to μ v\\bar v } ) Using the OPAL Detector at LEP * Status of Lepton Universality * QCD Predictions for the Tau Hadronic Width and Determination of α_s(M_τ ^{2}) * τ → π(K)ν and τ → ρν (OPAL Results) * Measurement of the Decay τ- → ρ-ντ * A Measurement of the Branching Fraction B(τ± → h±π0ντ) * One-Prong Tau Decays with Multiple π0's * Analysis of the Hadronic Final State in τ- → π-π-π+ντ * Observation of the Decay τ± → 3h±2π0ντ * Measurement of the Spectral Functions and Determination of the Strong Coupling Constant * 3-Prong τ Decays * CLEO-II Results on τ Decays to η * Strange Decays of the Tau Lepton * Tau Decay Puzzles and Possible Light Gluinos * Beyond the Standard Model in Tau Decays * A Measurement of the Tau Lepton Lifetime * Tau Lifetime Measurement Using the OPAL Detector at LEP * A Precise Measurement of the τ Lepton Lifetime * DELPHI τ Lifetime Measurements * L3 Tau Lifetime Measurement from 1991 Data * The Tau Branching Ratios * Are We Moving Toward a Balanced τ Budget? * Bell's Inequality and τ-Physics at LEP * Anomalous Magnetic Moment of the τ Lepton * Tests for CP Violation in τ Decays * CP Violation and τ Weak Dipole Moment * Search for CP Violation in Z → τ+τ- * Test of Electroweak Interactions at TRISTAN * Test of Electroweak Interactions at LEP * Measurement of τ Polarization at LEP * Tau Physics at p\\bar p Colliders * New Measurements of the Tau and Tau Neutrino Masses from

  16. Discodermolide interferes with the binding of tau protein to microtubules.

    PubMed

    Kar, Santwana; Florence, Gordon J; Paterson, Ian; Amos, Linda A

    2003-03-27

    We investigated whether discodermolide, a novel antimitotic agent, affects the binding to microtubules of tau protein repeat motifs. Like taxol, the new drug reduces the proportion of tau that pellets with microtubules. Despite their differing structures, discodermolide, taxol and tau repeats all bind to a site on beta-tubulin that lies within the microtubule lumen and is crucial in controlling microtubule assembly. Low concentrations of tau still bind strongly to the outer surfaces of preformed microtubules when the acidic C-terminal regions of at least six tubulin dimers are available for interaction with each tau molecule; otherwise binding is very weak.

  17. Curcumin Suppresses Soluble Tau Dimers and Corrects Molecular Chaperone, Synaptic, and Behavioral Deficits in Aged Human Tau Transgenic Mice*

    PubMed Central

    Ma, Qiu-Lan; Zuo, Xiaohong; Yang, Fusheng; Ubeda, Oliver J.; Gant, Dana J.; Alaverdyan, Mher; Teng, Edmond; Hu, Shuxin; Chen, Ping-Ping; Maiti, Panchanan; Teter, Bruce; Cole, Greg M.; Frautschy, Sally A.

    2013-01-01

    The mechanisms underlying Tau-related synaptic and cognitive deficits and the interrelationships between Tau species, their clearance pathways, and synaptic impairments remain poorly understood. To gain insight into these mechanisms, we examined these interrelationships in aged non-mutant genomic human Tau mice, with established Tau pathology and neuron loss. We also examined how these interrelationships changed with an intervention by feeding mice either a control diet or one containing the brain permeable beta-amyloid and Tau aggregate binding molecule curcumin. Transgene-dependent elevations in soluble and insoluble phospho-Tau monomer and soluble Tau dimers accompanied deficits in behavior, hippocampal excitatory synaptic markers, and molecular chaperones (heat shock proteins (HSPs)) involved in Tau degradation and microtubule stability. In human Tau mice but not control mice, HSP70, HSP70/HSP72, and HSP90 were reduced in membrane-enriched fractions but not in cytosolic fractions. The synaptic proteins PSD95 and NR2B were reduced in dendritic fields and redistributed into perikarya, corresponding to changes observed by immunoblot. Curcumin selectively suppressed levels of soluble Tau dimers, but not of insoluble and monomeric phospho-Tau, while correcting behavioral, synaptic, and HSP deficits. Treatment increased PSD95 co-immunoprecipitating with NR2B and, independent of transgene, increased HSPs implicated in Tau clearance. It elevated HSP90 and HSC70 without increasing HSP mRNAs; that is, without induction of the heat shock response. Instead curcumin differentially impacted HSP90 client kinases, reducing Fyn without reducing Akt. In summary, curcumin reduced soluble Tau and elevated HSPs involved in Tau clearance, showing that even after tangles have formed, Tau-dependent behavioral and synaptic deficits can be corrected. PMID:23264626

  18. Electrochemical detection of anti-tau antibodies binding to tau protein and inhibition of GSK-3β-catalyzed phosphorylation.

    PubMed

    Esteves-Villanueva, Jose O; Martic-Milne, Sanela

    2016-03-01

    Tau protein hyperphosphorylation triggers tau aggregation and its toxicity, leading to neuronal death and cell-to-cell toxicity. Hence, inhibition of protein kinases is a viable tool toward reduction of tau toxicity. By targeting various epitopes of Tau441 protein immobilized on Au surface, the protein kinase inhibition by anti-tau antibodies was measured by surface electrochemistry. The electrochemical impedance spectroscopy was used to measure the charge transfer resistance (Rct) of nonphosphorylated tau-Au film (nTau-Au) and compared with the phosphorylated tau-Au film (pTau-Au). The pTau-Au films were characterized by X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (TOF-SIMS), which indicated high phosphorus content. The Rct factor was used as the measure of inhibition efficacies by anti-tau antibodies (D8, A10, P262, and Tau46) in addition to antibody formulation intravenous immunoglobulin (IVIG). The Rct factor for pTau-Au in the absence of antibodies was 0.25 ± 0.08, indicating a dramatic decrease in Rct on phosphorylation. The Rct factors for Tau46 and A10 were 0.57 ± 0.22 and 0.65 ± 0.26, respectively, indicating phosphorylation inhibition. All antibodies exhibited similar binding to nTau-Au. The proposed electrochemical assay may be used for detection of other posttranslational modifications. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. The disk around the brown dwarf KPNO Tau 3

    SciTech Connect

    Broekhoven-Fiene, Hannah; Matthews, Brenda; Di Francesco, James; Duchêne, Gaspard; Scholz, Aleks; Chrysostomou, Antonio; Jayawardhana, Ray

    2014-07-10

    We present submillimeter observations of the young brown dwarfs KPNO Tau 1, KPNO Tau 3, and KPNO Tau 6 at 450 μm and 850 μm taken with the Submillimetre Common-User Bolometer Array on the James Clerk Maxwell Telescope. KPNO Tau 3 and KPNO Tau 6 have been previously identified as Class II objects hosting accretion disks, whereas KPNO Tau 1 has been identified as a Class III object and shows no evidence of circumsubstellar material. Our 3σ detection of cold dust around KPNO Tau 3 implies a total disk mass of (4.0 ± 1.1) × 10{sup –4} M{sub ☉} (assuming a gas to dust ratio of 100:1). We place tight constraints on any disks around KPNO Tau 1 or KPNO Tau 6 of <2.1 × 10{sup –4} M{sub ☉} and <2.7 × 10{sup –4} M{sub ☉}, respectively. Modeling the spectral energy distribution of KPNO Tau 3 and its disk suggests the disk properties (geometry, dust mass, and grain size distribution) are consistent with observations of other brown dwarf disks and low-mass T-Tauri stars. In particular, the disk-to-host mass ratio for KPNO Tau 3 is congruent with the scenario that at least some brown dwarfs form via the same mechanism as low-mass stars.

  20. Tau mis-splicing in the pathogenesis of neurodegenerative disorders.

    PubMed

    Park, Sun Ah; Ahn, Sang Il; Gallo, Jean-Marc

    2016-08-01

    Tau proteins, which stabilize the structure and regulate the dynamics of microtubules, also play important roles in axonal transport and signal transduction. Tau proteins are missorted, aggregated, and found as tau inclusions under many pathological conditions associated with neurodegenerative disorders, which are collectively known as tauopathies. In the adult human brain, tau protein can be expressed in six isoforms due to alternative splicing. The aberrant splicing of tau pre-mRNA has been consistently identified in a variety of tauopathies but is not restricted to these types of disorders as it is also present in patients with non-tau proteinopathies and RNAopathies. Tau mis-splicing results in isoform-specific impairments in normal physiological function and enhanced recruitment of excessive tau isoforms into the pathological process. A variety of factors are involved in the complex set of mechanisms underlying tau mis-splicing, but variation in the cis-element, methylation of the MAPT gene, genetic polymorphisms, the quantity and activity of spliceosomal proteins, and the patency of other RNA-binding proteins, are related to aberrant splicing. Currently, there is a lack of appropriate therapeutic strategies aimed at correcting the tau mis-splicing process in patients with neurodegenerative disorders. Thus, a more comprehensive understanding of the relationship between tau mis-splicing and neurodegenerative disorders will aid in the development of efficient therapeutic strategies for patients with a tauopathy or other, related neurodegenerative disorders. [BMB Reports 2016; 49(8): 405-413].

  1. Tau mis-splicing in the pathogenesis of neurodegenerative disorders

    PubMed Central

    Park, Sun Ah; Ahn, Sang Il; Gallo, Jean-Marc

    2016-01-01

    Tau proteins, which stabilize the structure and regulate the dynamics of microtubules, also play important roles in axonal transport and signal transduction. Tau proteins are missorted, aggregated, and found as tau inclusions under many pathological conditions associated with neurodegenerative disorders, which are collectively known as tauopathies. In the adult human brain, tau protein can be expressed in six isoforms due to alternative splicing. The aberrant splicing of tau pre-mRNA has been consistently identified in a variety of tauopathies but is not restricted to these types of disorders as it is also present in patients with non-tau proteinopathies and RNAopathies. Tau mis-splicing results in isoform-specific impairments in normal physiological function and enhanced recruitment of excessive tau isoforms into the pathological process. A variety of factors are involved in the complex set of mechanisms underlying tau mis-splicing, but variation in the cis-element, methylation of the MAPT gene, genetic polymorphisms, the quantity and activity of spliceosomal proteins, and the patency of other RNA-binding proteins, are related to aberrant splicing. Currently, there is a lack of appropriate therapeutic strategies aimed at correcting the tau mis-splicing process in patients with neurodegenerative disorders. Thus, a more comprehensive understanding of the relationship between tau mis-splicing and neurodegenerative disorders will aid in the development of efficient therapeutic strategies for patients with a tauopathy or other, related neurodegenerative disorders. [BMB Reports 2016; 49(8): 405-413] PMID:27222125

  2. RNA-Skim: a rapid method for RNA-Seq quantification at transcript level.

    PubMed

    Zhang, Zhaojun; Wang, Wei

    2014-06-15

    RNA-Seq technique has been demonstrated as a revolutionary means for exploring transcriptome because it provides deep coverage and base pair-level resolution. RNA-Seq quantification is proven to be an efficient alternative to Microarray technique in gene expression study, and it is a critical component in RNA-Seq differential expression analysis. Most existing RNA-Seq quantification tools require the alignments of fragments to either a genome or a transcriptome, entailing a time-consuming and intricate alignment step. To improve the performance of RNA-Seq quantification, an alignment-free method, Sailfish, has been recently proposed to quantify transcript abundances using all k-mers in the transcriptome, demonstrating the feasibility of designing an efficient alignment-free method for transcriptome quantification. Even though Sailfish is substantially faster than alternative alignment-dependent methods such as Cufflinks, using all k-mers in the transcriptome quantification impedes the scalability of the method. We propose a novel RNA-Seq quantification method, RNA-Skim, which partitions the transcriptome into disjoint transcript clusters based on sequence similarity, and introduces the notion of sig-mers, which are a special type of k-mers uniquely associated with each cluster. We demonstrate that the sig-mer counts within a cluster are sufficient for estimating transcript abundances with accuracy comparable with any state-of-the-art method. This enables RNA-Skim to perform transcript quantification on each cluster independently, reducing a complex optimization problem into smaller optimization tasks that can be run in parallel. As a result, RNA-Skim uses <4% of the k-mers and <10% of the CPU time required by Sailfish. It is able to finish transcriptome quantification in <10 min per sample by using just a single thread on a commodity computer, which represents >100 speedup over the state-of-the-art alignment-based methods, while delivering comparable or higher

  3. RNA-Skim: a rapid method for RNA-Seq quantification at transcript level

    PubMed Central

    Zhang, Zhaojun; Wang, Wei

    2014-01-01

    Motivation: RNA-Seq technique has been demonstrated as a revolutionary means for exploring transcriptome because it provides deep coverage and base pair-level resolution. RNA-Seq quantification is proven to be an efficient alternative to Microarray technique in gene expression study, and it is a critical component in RNA-Seq differential expression analysis. Most existing RNA-Seq quantification tools require the alignments of fragments to either a genome or a transcriptome, entailing a time-consuming and intricate alignment step. To improve the performance of RNA-Seq quantification, an alignment-free method, Sailfish, has been recently proposed to quantify transcript abundances using all k-mers in the transcriptome, demonstrating the feasibility of designing an efficient alignment-free method for transcriptome quantification. Even though Sailfish is substantially faster than alternative alignment-dependent methods such as Cufflinks, using all k-mers in the transcriptome quantification impedes the scalability of the method. Results: We propose a novel RNA-Seq quantification method, RNA-Skim, which partitions the transcriptome into disjoint transcript clusters based on sequence similarity, and introduces the notion of sig-mers, which are a special type of k-mers uniquely associated with each cluster. We demonstrate that the sig-mer counts within a cluster are sufficient for estimating transcript abundances with accuracy comparable with any state-of-the-art method. This enables RNA-Skim to perform transcript quantification on each cluster independently, reducing a complex optimization problem into smaller optimization tasks that can be run in parallel. As a result, RNA-Skim uses <4% of the k-mers and <10% of the CPU time required by Sailfish. It is able to finish transcriptome quantification in <10 min per sample by using just a single thread on a commodity computer, which represents >100 speedup over the state-of-the-art alignment-based methods, while delivering

  4. Effects of 3-repeat tau on taxol mobility through microtubules

    NASA Astrophysics Data System (ADS)

    Park, Hyunjoo; Fygenson, Deborah; Kim, Mahn Won

    2005-03-01

    Both the anti-cancer drug taxol and the microtubule-associated protein tau suppress dynamics of microtubules (MT). We have observed taxol mobility with full-length 3-repeat tau, one of six tau isoforms, using fluorescence recovery after photobleaching (FRAP) on MTs and compare with earlier results on recombinant full-length adult 4-repeat tau. Taxol mobility becomes highly sensitive to taxol concentration in the presence of 3-repeat tau (up to 1:1 molar ratio) as it does in the presence of 4-repeat tau, but is 2 to 3 times faster at low taxol concentrations. Fitting to a mean-field binding reaction model [J.L. Ross et.al, PNAS 101:12910-5 (2004)] suggests that the presence of 3-repeat tau enhances taxol movement through pores in the MT walls.

  5. Tau--an inhibitor of deacetylase HDAC6 function.

    PubMed

    Perez, Mar; Santa-Maria, Ismael; Gomez de Barreda, Elena; Zhu, Xiongwei; Cuadros, Raquel; Cabrero, Jose Roman; Sanchez-Madrid, Francisco; Dawson, Hana N; Vitek, Michael P; Perry, George; Smith, Mark A; Avila, Jesus

    2009-06-01

    Analysis of brain microtubule protein from patients with Alzheimer's disease showed decreased alpha tubulin levels along with increased acetylation of the alpha tubulin subunit, mainly in those microtubules from neurons containing neurofibrillary tau pathology. To determine the relationship of tau protein and increased tubulin acetylation, we studied the effect of tau on the acetylation-deacetylation of tubulin. Our results indicate that tau binds to the tubulin-deacetylase, histone deacetylase 6 (HDAC6), decreasing its activity with a consequent increase in tubulin acetylation. As expected, increased acetylation was also found in tubulin from wild-type mice compared with tubulin from mice lacking tau because of the tau-mediated inhibition of the deacetylase. In addition, we found that an excess of tau protein, as a HDAC6 inhibitor, prevents induction of autophagy by inhibiting proteasome function.

  6. Dimer model for Tau proteins bound in microtubule bundles

    NASA Astrophysics Data System (ADS)

    Hall, Natalie; Kluber, Alexander; Hayre, N. Robert; Singh, Rajiv; Cox, Daniel

    2013-03-01

    The microtubule associated protein tau is important in nucleating and maintaining microtubule spacing and structure in neuronal axons. Modification of tau is implicated as a later stage process in Alzheimer's disease, but little is known about the structure of tau in microtubule bundles. We present preliminary work on a proposed model for tau dimers in microtubule bundles (dimers are the minimal units since there is one microtubule binding domain per tau). First, a model of tau monomer was created and its characteristics explored using implicit solvent molecular dynamics simulation. Multiple simulations yield a partially collapsed form with separate positively/negatively charged clumps, but which are a factor of two smaller than required by observed microtubule spacing. We argue that this will elongate in dimer form to lower electrostatic energy at a cost of entropic ``spring'' energy. We will present preliminary results on steered molecular dynamics runs on tau dimers to estimate the actual force constant. Supported by US NSF Grant DMR 1207624.

  7. Inactivation of Listeria monocytogenes in Skim Milk and Liquid Egg White by Antimicrobial Bottle Coating with Polylactic Acid and Nisin

    USDA-ARS?s Scientific Manuscript database

    This study was to develop an antimicrobial bottle coating method to reduce the risk of outbreaks of human listeriosis caused by contaminated liquid foods. Liquid egg white and skim milk were inoculated with Listeria monocytogenes Scott A and stored in glass jars that were coated with a mixture of po...

  8. Total-tau and phospho-tau(181Thr) in cerebrospinal fluid of neurologically intact population increase with age.

    PubMed

    Jaworski, J; Psujek, M; Bartosik-Psujek, H

    2009-01-01

    Tau protein is a microtubule-associated molecule playing a crucial role in maintenance of neuronal integrity and in many neurodegenerative processes; its pathology has become a hallmark feature at the tissue level. The aim of the study was to estimate total tau and phospho-tau (Thr181) concentrations in cerebrospinal fluid of healthy population. Cerebrospinal fluid samples were taken from 129 subjects (age 18-77 years) without known neurologic or psychiatric condition. Both total-tau and phospho-tau levels showed significant correlation with age, which was more pronounced in older population.

  9. Characterization of tau oligomeric seeds in progressive supranuclear palsy.

    PubMed

    Gerson, Julia E; Sengupta, Urmi; Lasagna-Reeves, Cristian A; Guerrero-Muñoz, Marcos J; Troncoso, Juan; Kayed, Rakez

    2014-06-14

    Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy which is primarily defined by the deposition of tau into globose-type neurofibrillary tangles (NFT). Tau in its native form has important functions for microtubule dynamics. Tau undergoes alternative splicing in exons 2, 3, and 10 which results in six different isoforms. Products of splicing on exon 10 are the most prone to mutations. Three repeat (3R) and four repeat (4R) tau, like other disease-associated amyloids, can form oligomers which may then go on to further aggregate and form fibrils. Recent studies from our laboratory and others have provided evidence that tau oligomers, not NFTs, are the most toxic species in neurodegenerative tauopathies and seed the pathological spread of tau. Analysis of PSP brain sections revealed globose-type NFTs, as well as both phosphorylated and unphosphorylated tau oligomers. Analysis of PSP brains via Western blot and ELISA revealed the presence of increased levels of tau oligomers compared to age-matched control brains. Oligomers were immunoprecipitated from PSP brain and were capable of seeding the oligomerization of both 3R and 4R tau isoforms. This is the first time tau oligomers have been characterized in PSP. These results indicate that tau oligomers are an important component of PSP pathology, along with NFTs. The ability of PSP brain-derived tau oligomers to seed 3R and 4R tau suggests that these oligomers represent the pathological species responsible for disease propagation and the presence of oligomers in a pure neurodegenerative tauopathy implies a common neuropathological process for tau seen in diseases with other amyloid proteins.

  10. CSF tau and tau/Aβ42 predict cognitive decline in Parkinson’s disease

    PubMed Central

    Liu, Changqin; Cholerton, Brenna; Shi, Min; Ginghina, Carmen; Cain, Kevin C.; Auinger, Peggy; Zhang, Jing

    2015-01-01

    Introduction A substantial proportion of patients with Parkinson’s disease (PD) have concomitant cognitive dysfunction. Identification of biomarker profiles that predict which PD patients have a greater likelihood for progression of cognitive symptoms is pressingly needed for future treatment and prevention approaches. Methods Subjects were drawn from the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) study, a large clinical trial that enrolled initially untreated PD patients. For the current study, Phase One encompassed trial baseline until just prior to levodopa administration (n=403), and Phase Two spanned the initiation of levodopa treatment until the end of cognitive follow-up (n=305). Correlations and linear mixed models were performed to determine cross-sectional and longitudinal associations between baseline amyloid β1-42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) and measures of memory and executive function. Analyses also considered APOE genotype and tremor- vs. rigidity-dominant phenotype. Results No association was found between baseline CSF biomarkers and cognitive test performance during Phase One. However, once levodopa treatment was initiated, higher p-tau and p-tau/Aβ42 predicted subsequent decline on cognitive tasks involving both memory and executive functions. The interactions between biomarkers and cognition decline did not appear to be influenced by levodopa dosage, APOE genotype or motor phenotype. Conclusions The current study has, for the first time, demonstrated the possible involvement of tau species, whose gene (MAPT) has been consistently linked to the risk of PD by genome-wide association studies, in the progression of cognitive symptoms in PD. PMID:25596881

  11. Trans-splicing correction of tau isoform imbalance in a mouse model of tau mis-splicing.

    PubMed

    Avale, María Elena; Rodríguez-Martín, Teresa; Gallo, Jean-Marc

    2013-07-01

    Abnormal metabolism of the tau protein is central to the pathogenesis of a number of dementias, including Alzheimer's disease. Aberrant alternative splicing of exon 10 in the tau pre-mRNA resulting in an imbalance of tau isoforms is one of the molecular causes of the inherited tauopathy, FTDP-17. We showed previously in heterologous systems that exon 10 inclusion in tau mRNA could be modulated by spliceosome-mediated RNA trans-splicing (SMaRT). Here, we evaluated the potential of trans-splicing RNA reprogramming to correct tau mis-splicing in differentiated neurons in a mouse model of tau mis-splicing, the htau transgenic mouse line, expressing the human MAPT gene in a null mouse Mapt background. Trans-splicing molecules designed to increase exon 10 inclusion were delivered to neurons using lentiviral vectors. We demonstrate reprogramming of tau transcripts at the RNA level after transduction of cultured neurons or after direct delivery and long-term expression of viral vectors into the brain of htau mice in vivo. Tau RNA trans-splicing resulted in an increase in exon 10 inclusion in the mature tau mRNA. Importantly, we also show that the trans-spliced product is translated into a full-length chimeric tau protein. These results validate the potential of SMaRT to correct tau mis-splicing and provide a framework for its therapeutic application to neurodegenerative conditions linked to aberrant RNA processing.

  12. Nontargeted detection of adulteration of skim milk powder with foreign proteins using UHPLC-UV.

    PubMed

    Jablonski, Joseph E; Moore, Jeffrey C; Harnly, James M

    2014-06-04

    Chromatographic profiles of skim milk powder (SMP) and mixtures of SMP with soy (SPI), pea (PPI), brown rice (BRP), and hydrolyzed wheat protein (HWPI) isolates were obtained by ultrahigh-performance liquid chromatography (UHPLC) with 215 nm detection. Two data analysis approaches were compared for their utility to classify samples as authentic or adulterated. The t test approach evaluated data points exceeding the 99% confidence limit of the mean authentic SMP chromatogram and used data points from the entire chromatogram. The other approach used the multivariate Q statistic from a SIMCA model of authentic samples to determine adulteration and used a selected retention window to obtain best classifications. Q-Statistic and t test correctly classified adulteration of SMP with SPI at the 1% and 3% levels, respectively, while minimizing false classifications of authentic SMP. Detection of SMP adulterated with PPI, BRP, and HWPI was possible at higher adulteration levels.

  13. Universal ultrasonic goniometer for Rayleigh and surface skimming longitudinal wave dispersion measurements

    NASA Astrophysics Data System (ADS)

    Barth, M.; Küttner, M.; Köhler, B.; Bamberg, J.; Baron, H.-U.

    2012-05-01

    There are several approaches for determining the Rayleigh wave dispersion of surface treated materials. Most of them are based either on ultrasonic probes in contact technique or on laser excitation or detection of ultrasound. Disadvantages of these methods for in-service use are coupling problems (contact methods) and very high device costs (laser based methods). The paper presents an immersion technique trying to avoid the disadvantages of the previous approaches for practical use. The High precision Ultrasound Goniometer (HUGO) allows to vary both: the sound beam angles and the distance between the excitation and detection sound beams. Thus, the Rayleigh wave velocity and its dispersion can be determined by two independent methods: by the drop in the reflexion coefficient at the Rayleigh angle and by change in travel time for a given change in travel distance. The dispersion can also be determined for surface skimming longitudinal waves. The application for stress determination in surface treated aero-engine materials is discussed.

  14. Differential induction and spread of tau pathology in young PS19 tau transgenic mice following intracerebral injections of pathological tau from Alzheimer’s disease or corticobasal degeneration brains

    PubMed Central

    Boluda, Susana; Iba, Michiyo; Zhang, Bin; Raible, Kevin M.; Lee, Virginia M-Y.; Trojanowski, John Q.

    2015-01-01

    Filamentous tau pathologies are hallmark lesions of several neurodegenerative tauopathies including Alzheimer’s disease (AD) and corticobasal degeneration (CBD) which show cell type-specific and topographically distinct tau inclusions. Growing evidence supports templated transmission of tauopathies through functionally interconnected neuroanatomical pathways suggesting that different self-propagating strains of pathological tau could account for the diverse manifestations of neurodegenerative tauopathies. Here, we describe the rapid and distinct cell type-specific spread of pathological tau following intracerebral injections of CBD or AD brain extracts enriched in pathological tau (designated CBD-Tau and AD-Tau, respectively) in young human mutant P301S tau transgenic (Tg) mice (line PS19) ~6–9 months before they show onset of mutant tau transgene-induced tau pathology. At 1 month post-injection of CBD-Tau, tau inclusions developed predominantly in oligodendrocytes of the fimbria and white matter near the injection sites with infrequent intraneuronal tau aggregates. In contrast, injections of AD-Tau in young PS19 mice induced tau pathology predominantly in neuronal perikarya with little or no oligodendrocyte involvement 1 month post-injection. With longer post-injection survival intervals of up to 6 months, CBD-Tau- and AD-Tau-induced tau pathology spread to different brain regions distant from the injection sites while maintaining the cell type-specific pattern noted above. Finally, CA3 neuron loss was detected 3 months post-injection of AD-Tau but not CBD-Tau. Thus, AD-Tau and CBD-Tau represent specific pathological tau strains that spread differentially and may underlie distinct clinical and pathological features of these two tauopathies. Hence, these strains could become targets to develop disease-modifying therapies for CBD and AD. PMID:25534024

  15. Rennet-induced gelation of calcium and phosphate supplemented skim milk subjected to CO2 treatment.

    PubMed

    Guillaume, C; Gastaldi, E; Cuq, J-L; Marchesseau, S

    2004-10-01

    A Doehlert design was performed to study the effect of calcium and phosphate supplementation at 0 to 25 mmol/kg and 0 to 16 mmol/kg, respectively, on the rennet gelation of reconstituted skim milk subjected to pH-reversible CO(2) acidification. Supplemented reconstituted skim milk samples were acidified to pH 5.80 by the addition of CO(2) under pressure and depressurized under vacuum to restore the initial pH value. The second-order polynomial models satisfactorily predicted the effect of salt addition on the micellar molar Ca:P ratio and the average diameter of the casein micelles, whereas only trends were used in the analysis of the rennet-clotting behavior of salt-supplemented, CO(2)-treated milk. Whether added Ca was the most determinant factor on the micellar molar Ca:P ratio, added Pi (a mixture of Na(2)HPO(4) and NaH(2)PO(4)) was the most determinant factor on the other responses studied, and its effect was most pronounced when Ca was simultaneously added. By comparison with control samples, changes observed in this study were essentially due to salt supplementation and not to the CO(2) treatment. Therefore, this CO(2) treatment could be considered as an entirely reversible treatment rather than only pH-reversible, and predictions might be applied to untreated milk. In the case of Ca-supplemented milk, the micellar molar Ca:P ratio increased, the average micellar diameter decreased, and the rennet-clotting properties were improved, whereas opposite effects were observed upon Pi supplementation. Since modification of the micellar molar ratio is the result of change in the chemical composition of micellar calcium phosphate, the effect of calcium and phosphate supplementation on the rennet clotting of milk was found to be also dependent on the nature of the interaction between caseins and colloidal calcium phosphate.

  16. Physicochemical properties of skim milk powders prepared with the addition of mineral chelators.

    PubMed

    Sikand, V; Tong, P S; Vink, Sean; Roy, Soma

    2016-06-01

    The objective of this study was to determine the effect of mineral chelator addition during skim milk powder (SMP) manufacture on the solubility, turbidity, soluble protein, and heat stability (HS). Three chelators (sodium citrate dihydrate, sodium polyphosphate, and disodium EDTA) at 3 different concentrations (5, 15, and 25mM) were added to skim milk concentrate (30% total solids), and the pH was adjusted to 6.65 before spray drying to produce SMP. Spray-dried SMP samples were tested for solubility index (SI). Additionally, samples were reconstituted to contain 9% total solids, adjusted to pH 7.0, and tested for turbidity, protein content from supernatants of ultracentrifuged samples, and HS. Lower SI values were observed for samples treated with 5mM disodium EDTA and sodium polyphosphate than control samples or samples with 5mM sodium citrate dihydrate. Furthermore, lower SI values were observed with an increased level of chelating agents regardless of chelator type. A decreased turbidity value was found with increasing levels of mineral chelating salt treatment. Low turbidity with increasing levels of added chelators may be associated with the dissociation of caseins from micelles. Furthermore, higher protein content was observed in supernatants of ultracentrifuged samples treated with increased level of chelators as compared with the control sample. Higher HS was observed in samples treated with 5mM compared with samples treated with 25mM mineral chelator. The results suggest improved solubility and HS upon addition of mineral chelators to SMP during its manufacture. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  17. Unraveling duality violations in hadronic tau decays

    SciTech Connect

    Cata, Oscar; Cata, Oscar; Golterman, Maarten; Peris, Santiago

    2008-03-03

    There are some indications from recent determinations of the strong coupling constant alpha_s and the gluon condensate that the Operator Product Expansion may not be accurate enough to describe non-perturbative effects in hadronic tau decays. This breakdown of the Operator Product Expansion is usually referred to as being due to"Duality Violations." With the help of a physically motivated model, we investigate these duality violations. Based on this model, we argue how they may introduce a non-negligible systematic error in the current analysis, which employs finite-energy sum rules with pinched weights. In particular, this systematic effect might affect the precision determination of alpha_s from tau decays. With a view to a possible future application to real data, we present an alternative method for determining the OPE coefficients that might help estimating, and possibly even reducing, this systematic error.

  18. V409 Tau as Another AA Tau: Photometric Observations of Stellar Occultations by the Circumstellar Disk

    NASA Astrophysics Data System (ADS)

    Rodriguez, Joseph E.; Pepper, Joshua; Stassun, Keivan G.; Siverd, Robert J.; Cargile, Phillip; Weintraub, David A.; Beatty, Thomas G.; Gaudi, B. Scott; Mamajek, Eric E.; Sanchez, N. Nicole

    2015-07-01

    AA Tau is a well studied young stellar object (YSO) that presents many of the photometric characteristics of a Classical T Tauri star (CTTS), including short-timescale stochastic variability attributed to spots and/or accretion as well as long-duration dimming events attributed to occultations by vertical features (e.g., warps) in its circumstellar disk. We present new photometric observations of AA Tau from the Kilodegree Extremely Little Telescope North (KELT-North) which reveal a deep, extended dimming event in 2011, which we show supports the interpretation by Bouvier et al. of an occultation by a high-density feature in the circumstellar disk located \\gt 8 AU from the star. We also present KELT-North observations of V409 Tau, a relatively unstudied YSO also in Taurus-Auriga, showing short timescale erratic variability, along with two separate long and deep dimming events, one from 2009 January through late 2010 October, and the other from 2012 March until at least 2013 September. We interpret both dimming events to have lasted more than 600 days, each with a depth of ˜1.4 mag. From a spectral energy distribution analysis, we propose that V409 Tau is most likely surrounded by a circumstellar disk viewed nearly edge-on, and using Keplerian timescale arguments we interpret the deep dimmings of V409 Tau as occultations from one or more features within this disk ≳10 AU from the star. In both AA Tau and V409 Tau, the usual CTTS short-timescale variations associated with accretion processes close to the stars continue during the occultations, further supporting the distant occulting material interpretation. Like AA Tau, V409 Tau serves as a laboratory for studying the detailed structure of the protoplanetary environments of T Tauri disks, specifically disk structures that may be signposts of planet formation at many AU out in the disk. We also provide a table of all currently known disk-occulting young stars as a convenient reference for future work on such

  19. The Copernicus ultraviolet spectral atlas Tau Scorpii

    NASA Technical Reports Server (NTRS)

    Rogerson, J. B., Jr.; Upson, W. L., II

    1977-01-01

    An ultraviolet spectral atlas was presented for the B0 V star, Tau Scorpii. It was scanned from 949 to 1560 A by the Princeton spectrometer aboard the Copernicus satellite. From 949 to 1420 A the observations have a nominal resolution of 0.05 A. At the longer wavelengths, the resolution was 0.1 A. The atlas was presented in both tables and graphs.

  20. Maternal entrainment of tau mutant hamsters.

    PubMed

    Viswanathan, N; Davis, F C

    1992-01-01

    Maternal entrainment of the circadian wheel-running activity rhythm was examined in Syrian hamsters heterozygous for a single gene mutation (tau) that affects the free-running period of circadian rhythms. Heterozygous tau pups were born to and raised by wild-type mothers under constant dim light. The pups' wheel-running activity was recorded after weaning on postnatal day 18 or 24. Pups weaned on day 18 had an average free-running period of 21.70 hr, demonstrating that the tau phenotype was fully expressed at this age. Using the activity onset of the postnatal free-running rhythms as a phase reference, we estimated the phase relationships between the pups and their mothers on days 18 and 24. In contrast to results with wild-type pups, the activity rhythms of tau pups were not in phase with the rhythms of their wild-type mothers; that is, activity onsets of mothers and pups did not coincide. The pups did, however, show synchrony among themselves, indicating that they had been exposed to a synchronizing signal sometime during development. It is likely that this synchronizing signal was provided by the mothers, since pups from different litters showed phase relationships similar to those of their mothers. Thus the mothers provided a signal that was sufficient to cause entrainment, despite the 2-hr difference in free-running period between the mothers and pups. Although the pups' activity rhythms appeared to have been entrained by the mothers, they were clearly free-running by postnatal day 18. The mechanism for entrainment is lost during the course of development, despite continued interaction between the mothers and pups.

  1. Prompt {nu}{sub {tau}} fluxes in present and future {tau} neutrino experiments

    SciTech Connect

    Gonzalez-Garcia, M.C.; Gomez-Cadenas, J.J.

    1997-02-01

    We use a nonperturbative QCD approach, the quark-gluon string model, to compute the {tau}-neutrino fluxes produced by fixed target pA collisions (where A is a target material) for incident protons of energies ranging from 120 to 800 GeV. The purpose of this calculation is to estimate {ital in a consistent way} the prompt background for the {nu}{sub {mu}}({nu}{sub e}){leftrightarrow}{nu}{sub {tau}} oscillation search in the on-going {nu}{sub {mu}}({nu}{sub e}){leftrightarrow}{nu}{sub {tau}} oscillation search experiments CHORUS and NOMAD, as well as the expected prompt background in future experiments, such as COSMOS at Fermilab and a possible second-generation {nu}{sub {mu}}({nu}{sub e}){leftrightarrow}{nu}{sub {tau}} search experiment at the CERN SPS. In addition, we compute the number of {nu}{sub {tau}} interactions expected by the experiment E872 at Fermilab. {copyright} {ital 1997} {ital The American Physical Society}

  2. Hyperphosphorylation results in tau dysfunction in DNA folding and protection.

    PubMed

    Lu, Yang; He, Hai-Jin; Zhou, Jun; Miao, Jun-Ye; Lu, Jing; He, Ying-Ge; Pan, Rong; Wei, Yan; Liu, Ying; He, Rong-Qiao

    2013-01-01

    Hyperphosphorylation of tau occurs in preclinical and clinical stages of Alzheimer's disease (AD), and hyperphosphorylated tau is the main constituent of the paired helical filaments in the brains of mild cognitive impairment and AD patients. While most of the work described so far focused on the relationship between hyperphosphorylation of tau and microtubule disassembly as well as axonal transport impairments, both phenomena ultimately leading to cell death, little work has been done to study the correlation between tau hyperphosphorylation and DNA damage. As we showed in this study, tau hyperphosphorylation and DNA damage co-occurred under formaldehyde treatment in N2a cells, indicating that phosphorylated tau (p-Tau) induced by formaldehyde may be involved in DNA impairment. After phosphorylation, the effect of tau in preventing DNA from thermal denaturation was diminished, its ability to accelerate DNA renaturation was lost, and its function in protecting DNA from reactive oxygen species (ROS) attack was impaired. Thus, p-Tau is not only associated with the disassembly of the microtubule system, but also plays a crucial role in DNA impairment. Hyperphosphorylation-mediated dysfunction of tau protein in prevention of DNA structure from damage under the attack of ROS may provide novel insights into the mechanisms underlying tauopathies.

  3. Dopamine D2 Receptor antagonism suppresses tau aggregation and neurotoxicity

    PubMed Central

    McCormick, Allyson V.; Wheeler, Jeanna M.; Guthrie, Chris R.; Liachko, Nicole F.; Kraemer, Brian C.

    2012-01-01

    Background Tauopathies, including Alzheimer’s disease (AD) and frontotemporal dementia, are diseases characterized by the formation of pathological tau protein aggregates in the brain and progressive neurodegeneration. Presently no effective disease modifying treatments exist for tauopathies. Methods To identify drugs targeting tau neurotoxicity, we have used a C. elegans model of tauopathy to screen a drug library containing 1120 compounds approved for human use for the ability to suppress tau-induced behavioral effects. Results One compound, the typical antipsychotic azaperone, improved the motility of tau transgenic worms, reduced levels of insoluble tau, and was protective against neurodegeneration. We found that azaperone reduces insoluble tau in a human cell culture model of tau aggregation, and that other antipsychotic drugs (flupenthixol, perphenazine, and zotepine) also ameliorate the effects of tau expression in both models. Conclusions Reduction of dopamine signaling through the dopamine D2 receptor with the use of gene knockouts in C. elegans or RNAi knockdown in human cell culture have similar protective effects against tau toxicity. These results suggest dopamine D2 receptor antagonism holds promise as a potential neuroprotective strategy for targeting tau aggregation and neurotoxicity. PMID:23140663

  4. CSF tau levels influence cortical plasticity in Alzheimer's disease patients.

    PubMed

    Koch, Giacomo; Esposito, Zaira; Kusayanagi, Hajime; Monteleone, Fabrizia; Codecá, Claudia; Di Lorenzo, Francesco; Caltagirone, Carlo; Bernardi, Giorgio; Martorana, Alessandro

    2011-01-01

    Alzheimer's disease (AD) is a neurodegenerative process characterized by progressive neuronal degeneration, reduced levels of neurotransmitters, and altered forms of synaptic plasticity. In animal models of AD, amyloid-β (Aβ) and tau proteins are supposed to interfere with synaptic transmission. In the current study, we investigated the correlation between motor cortical plasticity, measured with 1 Hz repetitive transcranial magnetic stimulation (rTMS), and the levels of Aβ₁₋₄₂, total tau (t-Tau), and phosphorylated tau (p-Tau) detected in cerebrospinal fluid (CSF) of AD patients. We found that the overall rTMS after effects were milder in AD patients in comparison with controls. In AD patients the amount of rTMS-induced inhibition correlated with CSF t-Tau, but not with Aβ₁₋₄₂ CSF levels. Surprisingly, higher CSF t-Tau levels were associated to a stronger inhibition of the motor evoked potentials, implying that the expected effects of the 1 Hz rTMS protocol were more evident in patients with more pathological t-Tau CSF levels. These data could be interpreted as the consequence of CSF t-Tau mediated abnormal excitatory activity and could suggest that CSF t-Tau may impact mechanisms of cortical plasticity.

  5. Highly accurate tau-leaping methods with random corrections.

    PubMed

    Hu, Yucheng; Li, Tiejun

    2009-03-28

    We aim to construct higher order tau-leaping methods for numerically simulating stochastic chemical kinetic systems in this paper. By adding a random correction to the primitive tau-leaping scheme in each time step, we greatly improve the accuracy of the tau-leaping approximations. This gain in accuracy actually comes from the reduction in the local truncation error of the scheme in the order of tau, the marching time step size. While the local truncation error of the primitive tau-leaping method is O(tau(2)) for all moments, our Poisson random correction tau-leaping method, in which the correction term is a Poisson random variable, can reduce the local truncation error for the mean to O(tau(3)), and both Gaussian random correction tau-leaping methods, in which the correction term is a Gaussian random variable, can reduce the local truncation error for both the mean and covariance to O(tau(3)). Numerical results demonstrate that these novel methods more accurately capture crucial properties such as the mean and variance than existing methods for simulating chemical reaction systems. This work constitutes a first step to construct high order numerical methods for simulating jump processes. With further refinement and appropriately modified step-size selection procedures, the random correction methods should provide a viable way of simulating chemical reaction systems accurately and efficiently.

  6. Can numerical modeling help understand the fate of tau protein in the axon terminal?

    PubMed

    Kuznetsov, I A; Kuznetsov, A V

    2016-01-01

    In this paper, we used mathematical modeling to investigate the fate of tau protein in the axon terminal. We developed a comprehensive model of tau transport that accounts for transport of cytosolic tau by diffusion, diffusion transport of microtubule (MT)-bound tau along the MT lattice, active motor-driven transport of MT-bound tau via slow axonal transport mechanism, and degradation of tau in the axon due to tau's finite half-life. We investigated the effect of different assumptions concerning the fate of tau in the terminal on steady-state transport of tau in the axon. In particular, we studied two possible scenarios: (i) tau is destroyed in the terminal and (ii) there is no tau destruction in the terminal, and to avoid tau accumulation we postulated zero flux of tau at the terminal. We found that the tau concentration and percentage of MT-bound tau are not very sensitive to the assumption concerning the fate of tau in the terminal, but the tau's flux and average velocity of tau transport are very sensitive to this assumption. This suggests that measuring the velocity of tau transport and comparing it with the results of mathematical modeling for different assumptions concerning tau's fate in the terminal can provide information concerning what happens to tau in the terminal.

  7. Interactions between Aβ and Mutated Tau Lead to Polymorphism and Induce Aggregation of Aβ-Mutated Tau Oligomeric Complexes

    PubMed Central

    Raz, Yoav; Miller, Yifat

    2013-01-01

    One of the main hallmarks of the fronto-temporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) is the accumulation of neurofibrillary tangles in the brain as an outcome of the aggregation of mutated tau protein. This process occurs due to a number of genetic mutations in the MAPT gene. One of these mutations is the ∆K280 mutation in the tau R2 repeat domain, which promotes the aggregation vis-à-vis that for the wild-type tau. Experimental studies have shown that in Alzheimer’s disease Aβ peptide forms aggregates both with itself and with wild-type tau. By analogy, in FTDP-17, it is likely that there are interactions between Aβ and mutated tau, but the molecular mechanisms underlying such interactions remain to be elucidated. Thus, to investigate the interactions between Aβ and mutated tau, we constructed fourteen ∆K280 mutated tau-Aβ17-42 oligomeric complexes. In seven of the mutated tau-Aβ17-42 oligoemric complexes the mutated tau oligomers exhibited hydrophobic interactions in their core domain, and in the other seven mutated tau-Aβ17-42 oligoemric complexes the mutated tau oligomers exhibited salt-bridge interactions in their core domain. We considered two types of interactions between mutated tau oligomers and Aβ oligomers: interactions of one monomer of the Aβ oligomer with one monomer of the mutated tau oligomer to form a single-layer conformation, and interactions of the entire Aβ oligomer with the entire mutated tau oligomer to form a double-layer conformation. We also considered parallel arrangements of Aβ trimers alternating with mutated tau trimers in a single-layer conformation. Our results demonstrate that in the interactions of Aβ and mutated tau oligomers, polymorphic mutated tau-Aβ17-42 oligomeric complexes were observed, with a slight preference for the double-layer conformation. Aβ trimers alternating with mutated tau trimers constituted a structurally stable confined β-structure, albeit one that was

  8. Effect of microfiltration concentration factor on serum protein removal from skim milk using spiral-wound polymeric membranes.

    PubMed

    Beckman, S L; Barbano, D M

    2013-10-01

    Our objective was to determine the effect of concentration factor (CF) on the removal of serum protein (SP) from skim milk during microfiltration (MF) at 50 °C using a 0.3-μm-pore-size spiral-wound (SW) polymeric polyvinylidene fluoride (PVDF) membrane. Pasteurized (72°C for 16 s) skim milk was MF (50 °C) at 3 CF (1.50, 2.25, and 3.00×), each on a separate day of processing starting with skim milk. Two phases of MF were used at each CF, with an initial startup-stabilization phase (40 min in full recycle mode) to achieve the desired CF, followed by a steady-state phase (90-min feed-and-bleed with recycle) where data was collected. The experiment was replicated 3 times, and SP removal from skim milk was quantified at each CF. System pressures, flow rates, CF, and fluxes were monitored during the 90-min run. Permeate flux increased (12.8, 15.3, and 19.0 kg/m(2) per hour) with decreasing CF from 3.00 to 1.50×, whereas fouled water flux did not differ among CF, indicating that the effect of membrane fouling on hydraulic resistance of the membrane was similar at all CF. However, the CF used when microfiltering skim milk (50°C) with a 0.3-μm polymeric SW PVDF membrane did affect the percentage of SP removed. As CF increased from 1.50 to 3.00×, the percentage of SP removed from skim milk increased from 10.56 to 35.57%, in a single stage bleed-and-feed MF system. Percentage SP removal from skim milk was lower than the theoretical value. Rejection of SP during MF of skim milk with SW PVDF membranes was caused by fouling of the membrane, not by the membrane itself and differences in the foulant characteristic among CF influenced SP rejection more than it influenced hydraulic resistance. We hypothesize that differences in the conditions near the surface of the membrane and within the pores during the first few minutes of processing, when casein micelles pass through the membrane, influenced the rejection of SP because more pore size narrowing and plugging occurred at

  9. The CDF-II tau physics program triggers, tau ID and preliminary results

    SciTech Connect

    C. Pagliarone et al.

    2003-11-03

    The study of processes containing {tau} leptons in the final state will play an important role at Tevatron Run II. Such final states will be relevant both for electroweak studies and measurements as well as in searches for physics beyond the Standard Model. The present paper discusses the physics opportunities and challenges related to the implementation of new set of triggers able to select events containing tau candidates in the final state. They illustrate, in particular, the physics capabilities for a variety of new physics scenarios such as supersymmetry (SUSY), SUSY with Rp-parity violation, with Bilinear parity violation or models with the violation of lepton flavor. Finally, they present the first Run II results obtained using some of the described tau triggers.

  10. Tau flavored dark matter and its impact on tau Yukawa coupling

    NASA Astrophysics Data System (ADS)

    Chao, Wei; Guo, Huai-Ke; Li, Hao-Lin

    2017-02-01

    In this paper we perform a systematic study of the tau flavored dark matter (DM) model by introducing two kinds of mediators (a scalar doublet and a charged scalar singlet). The electromagnetic properties of the DM, as well as their implications in DM direct detections, are analyzed in detail. The model turns out contributing a significant radiative correction to the tau lepton mass, in addition to loosing the tension between the measured DM relic density and constraints of DM direct detections. The loop corrections can be Script O(10%) of the total tau mass. Signal rates of the Higgs measurements from the LHC in the h→τ τ and h→ γ γ channels, relative to the Standard Model expectations, can be explained in this model.

  11. Search for tau- ---> 4pi- 3pi+ (pi0) nu/tau Decays

    SciTech Connect

    Ter-Antonian, R.; Kass, R.; Allmendinger, T.; Hast, C.; /SLAC

    2005-06-21

    A search for the decay of the {tau} lepton to seven charged pions and at most one {pi}{sup 0} was performed using the BABAR detector at the PEP-II e{sup +}e{sup -} collider. The analysis uses data recorded on and near the {Upsilon}(4S) resonance between 1999 and 2003, a total of 124.3 fb{sup -1}. They observe 7 events with an expected background of 11.9 {+-} 2.2 events and calculate a preliminary upper limit of BR({tau}{sup -} {yields} 4{pi}{sup -} 3{pi}{sup +}({pi}{sup 0}){nu}{sub {tau}}) < 2.7 x 10{sup -7} at 90% CL. This is a significant improvement over the previous limit established by the CLEO Collaboration.

  12. Both total and phosphorylated tau are increased in Alzheimer's disease

    PubMed Central

    Sjogren, M; Davidsson, P; Tullberg, M; Minthon, L; Wallin, A; Wikkelso, C; Granerus, A; Vanderstichele, H; Vanmechelen, E; Blennow, K

    2001-01-01

    BACKROUND—Pathological tau protein concentrations in CSF are found in both Alzheimer's disease (AD) and frontotemporal dementia (FTD), but studies on brain tissue have suggested that the tau pathology in AD differs from that in FTD and that the difference may be related to the degree of phosphorylation. As CSF tau protein is increased after stroke, tau may also be implicated in the pathophysiology of vascular dementia, of which subcortical arteriosclerotic encephalopathy (SAE) is a putative subtype.
OBJECTIVES—To investigate the nature of tau protein in CSF and the involvement of total CSF tau and phosphorylated CSF tau (phosphotau) in various types of dementia.
METHODS—Using ELISAs for total tau and tau phosphorylated at Thr181 (phosphotau), the CSF concentrations of total tau and phosphotau were determined in patients with probable and possible AD (n=41 and 19, respectively), FTD (n=18), SAE (n=17), and Parkinson's disease (PD; n=15) and in age matched controls (n=17). All the antibodies stained the lower molecular weight bands, whereas only the antibodies that recognise phosphorylated tau stained the higher molecular bands.
RESULTS—Both CSF tau and CSF phosphotau were increased in probable AD compared with FTD (p<0.001), SAE (p<0.001), PD (p<0.001), and controls (p<0.001). CSF phosphotau was increased in possible AD compared with FTD (p<0.001) and SAE (p<0.001). CSF tau and CSF phosphotau were positively correlated in all the groups. Molecular weight forms of tau ranging from 25 kDa to 80 kDa were found in the CSF
CONCLUSION—Both phosphorylated and unphosphorylated tau isoforms were present in the CSF, and tau protein appeared in both truncated and full length forms. The results suggest that the CSF concentrations of tau and phosphotau are increased in about two thirds of patients with probable AD and in half of those with possible AD but are normal in FTD, SAE, and PD compared with normal aging. Values in the normal range do not exclude AD

  13. A Search for B+ --> tau + nu tau Recoiling Against B- --> D0 l- nu-bar l X

    SciTech Connect

    Sekula, Stephen J

    2003-03-24

    We present a search for the decay B{sup +} {yields} {tau}{sup +}{nu}{sub {tau}} in 88.9 x 10{sup 6} {Upsilon}(4S) decays recorded with the BABAR detector at the SLAC B-Factory. A sample of semi-exclusive, semi-leptonic B decays (B{sup -} {yields} D{sup 0}{ell}{sup -}{bar {nu}}{sub {ell}}X), where X is either a photon, {pi}{sup 0}, or nothing, is used to identify the daughter particles that are associated with the other B meson in each event. These particles are searched for evidence of a one-prong leptonic B{sup +} {yields} {tau}{sup +}{nu}{sub {tau}} decay. For this data sample we set a preliminary upper limit on the branching fraction of {Beta}(B{sup +} {yields} {tau}{sup +}{nu}{sub {tau}}) < 4.9 x 10{sup -4} at the 90% confidence level. This result is then combined with a statistically independent BABAR search for B{sup +} {yields} {tau}{sup +}{nu}{sub {tau}} to give a combined preliminary limit of {Beta}(B{sup +} {yields} {tau}{sup +}{nu}{sub {tau}}) < 4.1 x 10{sup -4}.

  14. AAV-mediated expression of anti-tau scFvs decreases tau accumulation in a mouse model of tauopathy.

    PubMed

    Ising, Christina; Gallardo, Gilbert; Leyns, Cheryl E G; Wong, Connie H; Stewart, Floy; Koscal, Lauren J; Roh, Joseph; Robinson, Grace O; Remolina Serrano, Javier; Holtzman, David M

    2017-05-01

    Tauopathies are characterized by the progressive accumulation of hyperphosphorylated, aggregated forms of tau. Our laboratory has previously demonstrated that passive immunization with an anti-tau antibody, HJ8.5, decreased accumulation of pathological tau in a human P301S tau-expressing transgenic (P301S-tg) mouse model of frontotemporal dementia/tauopathy. To investigate whether the Fc domain of HJ8.5 is required for the therapeutic effect, we engineered single-chain variable fragments (scFvs) derived from HJ8.5 with variable linker lengths, all specific to human tau. Based on different binding properties, we selected two anti-tau scFvs and tested their efficacy in vivo by adeno-associated virus-mediated gene transfer to the brain of P301S-tg mice. The scFvs significantly reduced levels of hyperphosphorylated, aggregated tau in brain tissue of P301S-tg mice, associated with a decrease in detergent-soluble tau species. Interestingly, these mice showed substantial levels of scFvs in the cerebrospinal fluid without significant effects on total extracellular tau levels. Therefore, our study provides a novel strategy for anti-tau immunotherapeutics that potentially limits a detrimental proinflammatory response. © 2017 Ising et al.

  15. Anti-tau antibodies that block tau aggregate seeding in vitro markedly decrease pathology and improve cognition in vivo

    PubMed Central

    Yanamandra, Kiran; Kfoury, Najla; Jiang, Hong; Mahan, Thomas E.; Ma, Shengmei; Maloney, Susan E.; Wozniak, David F.

    2014-01-01

    Summary Tau aggregation occurs in neurodegenerative diseases including Alzheimer's disease and many other disorders collectively termed tauopathies. Trans-cellular propagation of tau pathology, mediated by extracellular tau aggregates, may underlie pathogenesis of these conditions. P301S tau transgenic mice express mutant human tau protein, and develop progressive tau pathology. Using a cell-based biosensor assay, we screened anti-tau monoclonal antibodies for their ability to block seeding activity present in P301S brain lysates. We infused 3 effective antibodies or controls into the lateral ventricle of P301S mice for 3 months. The antibodies markedly reduced hyperphosphorylated, aggregated, and insoluble tau. They also blocked development of tau seeding activity detected in brain lysates using the biosensor assay, reduced microglial activation, and improved cognitive deficits. These data imply a central role for extracellular tau aggregates in the development of pathology. They also suggest immunotherapy specifically designed to block trans-cellular aggregate propagation will be a productive treatment strategy. PMID:24075978

  16. Anti-tau antibodies that block tau aggregate seeding in vitro markedly decrease pathology and improve cognition in vivo.

    PubMed

    Yanamandra, Kiran; Kfoury, Najla; Jiang, Hong; Mahan, Thomas E; Ma, Shengmei; Maloney, Susan E; Wozniak, David F; Diamond, Marc I; Holtzman, David M

    2013-10-16

    Tau aggregation occurs in neurodegenerative diseases including Alzheimer's disease and many other disorders collectively termed tauopathies. trans-cellular propagation of tau pathology, mediated by extracellular tau aggregates, may underlie pathogenesis of these conditions. P301S tau transgenic mice express mutant human tau protein and develop progressive tau pathology. Using a cell-based biosensor assay, we screened anti-tau monoclonal antibodies for their ability to block seeding activity present in P301S brain lysates. We infused three effective antibodies or controls into the lateral ventricle of P301S mice for 3 months. The antibodies markedly reduced hyperphosphorylated, aggregated, and insoluble tau. They also blocked development of tau seeding activity detected in brain lysates using the biosensor assay, reduced microglial activation, and improved cognitive deficits. These data imply a central role for extracellular tau aggregates in the development of pathology. They also suggest that immunotherapy specifically designed to block trans-cellular aggregate propagation will be a productive treatment strategy.

  17. Resonance Effective Theory Approach to {tau} {yields} 3{pi}{nu}{tau} Decays

    SciTech Connect

    Gomez Dumm, D.; Pich, A.; Portoles, J.

    2004-12-02

    The decays {tau} {yields} 3{pi}{nu}{tau} are analyzed in the framework of the resonance effective theory of QCD, We derive the effective chiral Lagrangian relevant for the evaluation of the hadronic axial-vector current, taking into account the constraints imposed by QCD on the high energy asymptotic behaviour. Then we fit the unknown parameters to the spectral function and branching ratio measured by ALEPH, showing that the theory is in good agreement with experimental data. A detailed description of the work sketched here can be found.

  18. Tau protein is essential for stress-induced brain pathology

    PubMed Central

    Lopes, Sofia; Vaz-Silva, João; Pinto, Vitor; Dalla, Christina; Kokras, Nikolaos; Bedenk, Benedikt; Mack, Natalie; Czisch, Michael; Almeida, Osborne F. X.; Sousa, Nuno; Sotiropoulos, Ioannis

    2016-01-01

    Exposure to chronic stress is frequently accompanied by cognitive and affective disorders in association with neurostructural adaptations. Chronic stress was previously shown to trigger Alzheimer’s-like neuropathology, which is characterized by Tau hyperphosphorylation and missorting into dendritic spines followed by memory deficits. Here, we demonstrate that stress-driven hippocampal deficits in wild-type mice are accompanied by synaptic missorting of Tau and enhanced Fyn/GluN2B-driven synaptic signaling. In contrast, mice lacking Tau [Tau knockout (Tau-KO) mice] do not exhibit stress-induced pathological behaviors and atrophy of hippocampal dendrites or deficits of hippocampal connectivity. These findings implicate Tau as an essential mediator of the adverse effects of stress on brain structure and function. PMID:27274066

  19. CP violation in Semi-Leptonic {tau} decays

    SciTech Connect

    Delepine, David

    2007-06-19

    We study CP violation in semi-leptonic {tau} decays and we determine the conditions necessary to be able to define a observable CP asymmetry. We apply these conditions in both models, the standard model for the electroweak interactions and its supersymmetric extensions. In the first case, the leading order contribution to the direct CP asymmetry in {tau}{+-} {yields} K{+-}{pi}0{nu}{tau} decay rates is evaluated. In the second case,we compute the SUSY effective hamiltonian that describes the |{delta}S| = 1 semileptonic decays of tau leptons. We show that SUSY contributions may enhance the CP asymmetry of {tau} {yields} K{pi}{nu}{tau} decays by several orders of magnitude compared to the standard model expectations.

  20. Tau as a therapeutic target in neurodegenerative disease

    PubMed Central

    Himmelstein, Diana S.; Ward, Sarah M.; Lancia, Jody K.; Patterson, Kristina R.

    2013-01-01

    Tau is a microtubule-associated protein thought to help modulate the stability of neuronal microtubules. In tauopathies, including Alzheimer’s disease and several frontotemporal dementias, tau is abnormally modified and misfolded resulting in its disassociation from microtubules and the generation of pathological lesions characteristic for each disease. A recent surge in the population of people with neurodegenerative tauopathies has highlighted the immense need for disease-modifying therapies for these conditions, and new attention has focused on tau as a potential target for intervention. In the current work we summarize evidence linking tau to disease pathogenesis and review recent therapeutic approaches aimed at ameliorating tau dysfunction. The primary therapeutic tactics considered include kinase inhibitors and phosphatase activators, immunotherapies, small molecule inhibitors of protein aggregation, and microtubule-stabilizing agents. Although the evidence for tau-based treatments is encouraging, additional work is undoubtedly needed to optimize each treatment strategy for the successful development of safe and effective therapeutics. PMID:22790092

  1. PET Imaging of Tau Deposition in the Aging Human Brain

    DOE PAGES

    Schöll, Michael; Lockhart, Samuel N.; Schonhaut, Daniel R.; ...

    2016-03-02

    Tau pathology is a hallmark of Alzheimer’s disease (AD) but also occurs in normal cognitive aging. In this study, using the tau PET agent 18F-AV-1451, we examined retention patterns in cognitively normal older people in relation to young controls and AD patients. Age and β-amyloid (measured using PiB PET) were differentially associated with tau tracer retention in healthy aging. Older age was related to increased tracer retention in regions of the medial temporal lobe, which predicted worse episodic memory performance. PET detection of tau in other isocortical regions required the presence of cortical β-amyloid and was associated with decline inmore » global cognition. Furthermore, patterns of tracer retention corresponded well with Braak staging of neurofibrillary tau pathology. In conclusion, the present study defined patterns of tau tracer retention in normal aging in relation to age, cognition, and β-amyloid deposition.« less

  2. PET Imaging of Tau Deposition in the Aging Human Brain

    SciTech Connect

    Schöll, Michael; Lockhart, Samuel N.; Schonhaut, Daniel R.; O’Neil, James P.; Janabi, Mustafa; Ossenkoppele, Rik; Baker, Suzanne L.; Vogel, Jacob W.; Faria, Jamie; Schwimmer, Henry D.; Rabinovici, Gil D.; Jagust, William J.

    2016-03-02

    Tau pathology is a hallmark of Alzheimer’s disease (AD) but also occurs in normal cognitive aging. In this study, using the tau PET agent 18F-AV-1451, we examined retention patterns in cognitively normal older people in relation to young controls and AD patients. Age and β-amyloid (measured using PiB PET) were differentially associated with tau tracer retention in healthy aging. Older age was related to increased tracer retention in regions of the medial temporal lobe, which predicted worse episodic memory performance. PET detection of tau in other isocortical regions required the presence of cortical β-amyloid and was associated with decline in global cognition. Furthermore, patterns of tracer retention corresponded well with Braak staging of neurofibrillary tau pathology. In conclusion, the present study defined patterns of tau tracer retention in normal aging in relation to age, cognition, and β-amyloid deposition.

  3. Search for the rare leptonic decay B--->tau-nutau.

    PubMed

    Aubert, B; Barate, R; Boutigny, D; Couderc, F; Gaillard, J-M; Hicheur, A; Karyotakis, Y; Lees, J P; Tisserand, V; Zghiche, A; Palano, A; Pompili, A; Chen, J C; Qi, N D; Rong, G; Wang, P; Zhu, Y S; Eigen, G; Ofte, I; Stugu, B; Abrams, G S; Borgland, A W; Breon, A B; Brown, D N; Button-Shafer, J; Cahn, R N; Charles, E; Day, C T; Gill, M S; Gritsan, A V; Groysman, Y; Jacobsen, R G; Kadel, R W; Kadyk, J; Kerth, L T; Kolomensky, Yu G; Kukartsev, G; Lynch, G; Mir, L M; Oddone, P J; Orimoto, T J; Pripstein, M; Roe, N A; Ronan, M T; Shelkov, V G; Wenzel, W A; Barrett, M; Ford, K E; Harrison, T J; Hart, A J; Hawkes, C M; Morgan, S E; Watson, A T; Fritsch, M; Goetzen, K; Held, T; Koch, H; Lewandowski, B; Pelizaeus, M; Steinke, M; Boyd, J T; Chevalier, N; Cottingham, W N; Kelly, M P; Latham, T E; Wilson, F F; Cuhadar-Donszelmann, T; Hearty, C; Knecht, N S; Mattison, T S; McKenna, J A; Thiessen, D; Khan, A; Kyberd, P; Teodorescu, L; Blinov, A E; Blinov, V E; Druzhinin, V P; Golubev, V B; Ivanchenko, V N; Kravchenko, E A; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Yushkov, A N; Best, D; Bruinsma, M; Chao, M; Eschrich, I; Kirkby, D; Lankford, A J; Mandelkern, M; Mommsen, R K; Roethel, W; Stoker, D P; Buchanan, C; Hartfiel, B L; Foulkes, S D; Gary, J W; Shen, B C; Wang, K; Del Re, D; Hadavand, H K; Hill, E J; Macfarlane, D B; Paar, H P; Rahatlou, Sh; Sharma, V; Berryhill, J W; Campagnari, C; Dahmes, B; Levy, S L; Long, O; Lu, A; Mazur, M A; Richman, J D; Verkerke, W; Beck, T W; Eisner, A M; Heusch, C A; Lockman, W S; Nesom, G; Schalk, T; Schmitz, R E; Schumm, B A; Seiden, A; Spradlin, P; Williams, D C; Wilson, M G; Albert, J; Chen, E; Dubois-Felsmann, G P; Dvoretskii, A; Hitlin, D G; Narsky, I; Piatenko, T; Porter, F C; Ryd, A; Samuel, A; Yang, S; Jayatilleke, S; Mancinelli, G; Meadows, B T; Sokoloff, M D; Abe, T; Blanc, F; Bloom, P; Chen, S; Ford, W T; Nauenberg, U; Olivas, A; Rankin, P; Smith, J G; Zhang, J; Zhang, L; Chen, A; Harton, J L; Soffer, A; Toki, W H; Wilson, R J; Zeng, Q L; Altenburg, D; Brandt, T; Brose, J; Dickopp, M; Feltresi, E; Hauke, A; Lacker, H M; Müller-Pfefferkorn, R; Nogowski, R; Otto, S; Petzold, A; Schubert, J; Schubert, K R; Schwierz, R; Spaan, B; Sundermann, J E; Bernard, D; Bonneaud, G R; Brochard, F; Grenier, P; Schrenk, S; Thiebaux, Ch; Vasileiadis, G; Verderi, M; Bard, D J; Clark, P J; Lavin, D; Muheim, F; Playfer, S; Xie, Y; Andreotti, M; Azzolini, V; Bettoni, D; Bozzi, C; Calabrese, R; Cibinetto, G; Luppi, E; Negrini, M; Piemontese, L; Sarti, A; Treadwell, E; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Finocchiaro, G; Patteri, P; Piccolo, M; Zallo, A; Buzzo, A; Capra, R; Contri, R; Crosetti, G; Lo Vetere, M; Macri, M; Monge, M R; Passaggio, S; Patrignani, C; Robutti, E; Santroni, A; Tosi, S; Bailey, S; Brandenburg, G; Morii, M; Won, E; Dubitzky, R S; Langenegger, U; Bhimji, W; Bowerman, D A; Dauncey, P D; Egede, U; Gaillard, J R; Morton, G W; Nash, J A; Nikolich, M B; Taylor, G P; Charles, M J; Grenier, G J; Mallik, U; Cochran, J; Crawley, H B; Lamsa, J; Meyer, W T; Prell, S; Rosenberg, E I; Yi, J; Davier, M; Grosdidier, G; Höcker, A; Laplace, S; Le Diberder, F; Lepeltier, V; Lutz, A M; Petersen, T C; Plaszczynski, S; Schune, M H; Tantot, L; Wormser, G; Cheng, C H; Lange, D J; Simani, M C; Wright, D M; Bevan, A J; Chavez, C A; Coleman, J P; Forster, I J; Fry, J R; Gabathuler, E; Gamet, R; Parry, R J; Payne, D J; Sloane, R J; Touramanis, C; Back, J J; Cormack, C M; Harrison, P F; Di Lodovico, F; Mohanty, G B; Brown, C L; Cowan, G; Flack, R L; Flaecher, H U; Green, M G; Jackson, P S; McMahon, T R; Ricciardi, S; Salvatore, F; Winter, M A; Brown, D; Davis, C L; Allison, J; Barlow, N R; Barlow, R J; Hodgkinson, M C; Lafferty, G D; Lyon, A J; Williams, J C; Farbin, A; Hulsbergen, W D; Jawahery, A; Kovalskyi, D; Lae, C K; Lillard, V; Roberts, D A; Blaylock, G; Dallapiccola, C; Flood, K T; Hertzbach, S S; Kofler, R; Koptchev, V B; Moore, T B; Saremi, S; Staengle, H; Willocq, S; Cowan, R; Sciolla, G; Taylor, F; Yamamoto, R K; Mangeol, D J J; Patel, P M; Robertson, S H; Lazzaro, A; Palombo, F; Bauer, J M; Cremaldi, L; Eschenburg, V; Godang, R; Kroeger, R; Reidy, J; Sanders, D A; Summers, D J; Zhao, H W; Brunet, S; Côté, D; Taras, P; Nicholson, H; Fabozzi, F; Gatto, C; Lista, L; Monorchio, D; Paolucci, P; Piccolo, D; Sciacca, C; Baak, M; Bulten, H; Raven, G; Snoek, H L; Wilden, L; Jessop, C P; Losecco, J M; Gabriel, T A; Allmendinger, T; Brau, B; Gan, K K; Honscheid, K; Hufnagel, D; Kagan, H; Kass, R; Pulliam, T; Rahimi, A M; Ter-Antonyan, R; Wong, Q K; Brau, J; Frey, R; Igonkina, O; Potter, C T; Sinev, N B; Strom, D; Torrence, E; Colecchia, F; Dorigo, A; Galeazzi, F; Margoni, M; Morandin, M; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Tiozzo, G; Voci, C; Benayoun, M; Briand, H; Chauveau, J; David, P; de la Vaissière, Ch; Del Buono, L; Hamon, O; John, M J J; Leruste, Ph; Malcles, J; Ocariz, J; Pivk, M; Roos, L; T'jampens, S; Therin, G; Manfredi, P F; Re, V; Behera, P K; Gladney, L; Guo, Q H; Panetta, J; Anulli, F; Biasini, M; Peruzzi, I M; Pioppi, M; Angelini, C; Batignani, G; Bettarini, S; Bondioli, M; Bucci, F; Calderini, G; Carpinelli, M; Forti, F; Giorgi, M A; Lusiani, A; Marchiori, G; Martinez-Vidal, F; Morganti, M; Neri, N; Paoloni, E; Rama, M; Rizzo, G; Sandrelli, F; Walsh, J; Haire, M; Judd, D; Paick, K; Wagoner, D E; Danielson, N; Elmer, P; Lau, Y P; Lu, C; Miftakov, V; Olsen, J; Smith, A J S; Telnov, A V; Bellini, F; Cavoto, G; Faccini, R; Ferrarotto, F; Ferroni, F; Gaspero, M; Li Gioi, L; Mazzoni, M A; Morganti, S; Pierini, M; Piredda, G; Tehrani, F Safai; Voena, C; Christ, S; Wagner, G; Waldi, R; Adye, T; De Groot, N; Franek, B; Geddes, N I; Gopal, G P; Olaiya, E O; Aleksan, R; Emery, S; Gaidot, A; Ganzhur, S F; Giraud, P-F; de Monchenault, G Hamel; Kozanecki, W; Langer, M; Legendre, M; London, G W; Mayer, B; Schott, G; Vasseur, G; Yèche, Ch; Zito, M; Purohit, M V; Weidemann, A W; Wilson, J R; Yumiceva, F X; Aston, D; Bartoldus, R; Berger, N; Boyarski, A M; Buchmueller, O L; Claus, R; Convery, M R; Cristinziani, M; De Nardo, G; Dong, D; Dorfan, J; Dujmic, D; Dunwoodie, W; Elsen, E E; Fan, S; Field, R C; Glanzman, T; Gowdy, S J; Hadig, T; Halyo, V; Hast, C; Hryn'ova, T; Innes, W R; Kelsey, M H; Kim, P; Kocian, M L; Leith, D W G S; Libby, J; Luitz, S; Luth, V; Lynch, H L; Marsiske, H; Messner, R; Muller, D R; O'Grady, C P; Ozcan, V E; Perazzo, A; Perl, M; Petrak, S; Ratcliff, B N; Roodman, A; Salnikov, A A; Schindler, R H; Schwiening, J; Simi, G; Snyder, A; Soha, A; Stelzer, J; Su, D; Sullivan, M K; Va'vra, J; Wagner, S R; Weaver, M; Weinstein, A J R; Wisniewski, W J; Wittgen, M; Wright, D H; Yarritu, A K; Young, C C; Burchat, P R; Edwards, A J; Meyer, T I; Petersen, B A; Roat, C; Ahmed, S; Alam, M S; Ernst, J A; Saeed, M A; Saleem, M; Wappler, F R; Bugg, W; Krishnamurthy, M; Spanier, S M; Eckmann, R; Kim, H; Ritchie, J L; Satpathy, A; Schwitters, R F; Izen, J M; Kitayama, I; Lou, X C; Ye, S; Bianchi, F; Bona, M; Gallo, F; Gamba, D; Borean, C; Bosisio, L; Cartaro, C; Cossutti, F; Della Ricca, G; Dittongo, S; Grancagnolo, S; Lanceri, L; Poropat, P; Vitale, L; Vuagnin, G; Panvini, R S; Banerjee, Sw; Brown, C M; Fortin, D; Jackson, P D; Kowalewski, R; Roney, J M; Sobie, R J; Band, H R; Dasu, S; Datta, M; Eichenbaum, A M; Graham, M; Hollar, J J; Johnson, J R; Kutter, P E; Li, H; Liu, R; Mihalyi, A; Mohapatra, A K; Pan, Y; Prepost, R; Rubin, A E; Sekula, S J; Tan, P; von Wimmersperg-Toeller, J H; Wu, J; Wu, S L; Yu, Z; Greene, M G; Neal, H

    2005-07-22

    We present a search for the decay B(-)--> tau(-)nu(tau) in a sample of 88.9 x 10(6) BB pairs recorded with the BABAR detector at the Stanford Linear Accelerator Center B factory. One of the two B mesons from the Gamma(4S) is reconstructed in a hadronic or a semileptonic final state, and the decay products of the other B in the event are analyzed for consistency with a B(-) --> tau(-)nu(tau) decay. We find no evidence of a signal and set an upper limit on the branching fraction of B(B(-) --> tau(-) nu(tau)) < 4.2 x 10(-4) at the 90% confidence level.

  4. Human protein tau represses DNA replication in vitro.

    PubMed

    Li, Wen; Wang, Xing Sheng; Qu, M H; Liu, Ying; He, Rong Qiao

    2005-11-30

    Here, in the experiments of both PCR and real-time PCR, a repression of DNA amplification was observed in the presence of protein tau. Furthermore, a strong repression appeared when an in vitro DNA replication assay was performed at the physiological temperature (37 degrees C). The incorporation of dNTP was markedly decreased to approximately 12% of control by the presence of tau23 and to approximately 15% by tau40. In the competitive experiments, the PCR product could be restored when the competitor DNA was added, indicating that the association of tau with the template gave rise to the repression. However, tau did not repress the yield of RNA in transcription, suggesting that tau was replaced or ejected from the template by the elongating T7 RNA polymerase.

  5. PET Imaging of Tau Deposition in the Aging Human Brain

    PubMed Central

    Schonhaut, Daniel R.; O’Neil, James P.; Janabi, Mustafa; Ossenkoppele, Rik; Baker, Suzanne L.; Vogel, Jacob W.; Faria, Jamie; Schwimmer, Henry D.; Rabinovici, Gil D.; Jagust, William J.

    2016-01-01

    SUMMARY Tau pathology is a hallmark of Alzheimer’s disease (AD) but also occurs in normal cognitive aging. Using the tau PET agent 18F-AV-1451, we examined retention patterns in cognitively normal older people in relation to young controls and AD patients. Age and β-amyloid (measured using PiB PET) were differentially associated with tau tracer retention in healthy aging. Older age was related to increased tracer retention in regions of the medial temporal lobe, which predicted worse episodic memory performance. PET detection of tau in other isocortical regions required the presence of cortical β-amyloid, and was associated with decline in global cognition. Furthermore, patterns of tracer retention corresponded well with Braak staging of neurofibrillary tau pathology. The present study defined patterns of tau tracer retention in normal aging in relation to age, cognition, and β-amyloid deposition. PMID:26938442

  6. Modification of Tau by 8-Nitroguanosine 3',5'-Cyclic Monophosphate (8-Nitro-cGMP): EFFECTS OF NITRIC OXIDE-LINKED CHEMICAL MODIFICATION ON TAU AGGREGATION.

    PubMed

    Yoshitake, Jun; Soeda, Yoshiyuki; Ida, Tomoaki; Sumioka, Akio; Yoshikawa, Misato; Matsushita, Kenji; Akaike, Takaaki; Takashima, Akihiko

    2016-10-21

    Neurofibrillar tangles caused by intracellular hyperphosphorylated tau inclusion and extracellular amyloid β peptide deposition are hallmarks of Alzheimer's disease. Tau contains one or two cysteine residues in three or four repeats of the microtubule binding region following alternative splicing of exon 10, and formation of intermolecular cysteine disulfide bonds accelerates tau aggregation. 8-Nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) acts as a novel second messenger of nitric oxide (NO) by covalently binding cGMP to cysteine residues by electrophilic properties, a process termed protein S-guanylation. Here we studied S-guanylation of tau and its effects on tau aggregation. 8-Nitro-cGMP exposure induced S-guanylation of tau both in vitro and in tau-overexpressed HEK293T cells. S-guanylated tau inhibited heparin-induced tau aggregation in a thioflavin T assay. Atomic force microscopy observations indicated that S-guanylated tau could not form tau granules and fibrils. Further biochemical analyses showed that S-guanylated tau was inhibited at the step of tau oligomer formation. In P301L tau-expressing Neuro2A cells, 8-nitro-cGMP treatment significantly reduced the amount of sarcosyl-insoluble tau. NO-linked chemical modification on cysteine residues of tau could block tau aggregation, and therefore, increasing 8-nitro-cGMP levels in the brain could become a potential therapeutic strategy for Alzheimer's disease. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Global Conformation of Tau Protein Mapped by Raman Spectroscopy.

    PubMed

    Gorantla, Nalini Vijay; Khandelwal, Puneet; Poddar, Pankaj; Chinnathambi, Subashchandrabose

    2017-01-01

    Alzheimer's disease (AD) is one of the neurodegenerative disease characterized by progressive neuronal loss in the brain. Its two major hallmarks are extracellular senile plaques and intracellular neurofibrillary tangles (NFTs), formed by aggregation of amyloid β-42 (Aβ-42) and Tau protein respectively. Aβ-42 is a transmembrane protein, which is produced after the sequential action of β- and γ-secretases, thus obtained peptide is released extracellularly and gets deposited on the neuron forming senile plaques. NFTs are composed of microtubule-associated protein-Tau (MAPT). Tau protein's major function is to stabilize the microtubule that provides a track on which the cargo proteins are shuttled and the stabilized microtubule also maintains shape and integrity of the neuronal cell. Tau protein is subjected to various modifications such as phosphorylation, ubiquitination, glycation, acetylation, truncation, glycosylation, deamination, and oxidation; these modifications ultimately lead to its aggregation. Phosphorylation is the major modification and is extensively studied with respect to Tau protein. Tau protein, however, undergoes certain level of phosphorylation and dephosphorylation, which regulates its affinity for microtubule and ultimately leading to microtubule assembly and disassembly. Our main aim was to study the native state of longest isoform of Tau (hTau40WT-4R2N) and its shortest isoform, (hTau23WT-3R0N), at various temperatures such as 10, 25, and 37 °C. Raman spectroscopic results suggested that the proportion of random coils or unordered structure depends on the temperature of the protein environment. Upon increase in the temperature from 10 to 37 °C, the proportion of random coils or unordered structures increased in the case of hTau40WT. However, we did not find a significant effect of temperature on the structure of hTau23WT. This current approach enables one to analyze the global conformation of soluble Tau in solution.

  8. Cellular factors modulating the mechanism of tau protein aggregation

    PubMed Central

    Fontaine, Sarah N.; Sabbagh, Jonathan J.; Baker, Jeremy; Martinez-Licha, Carlos R.; Darling, April

    2015-01-01

    Pathological accumulation of the microtubule-associated protein tau, in the form of neurofibrillary tangles, is a major hallmark of Alzheimer’s disease, the most prevalent neurodegenerative condition worldwide. In addition to Alzheimer’s disease, a number of neurodegenerative diseases, called tauopathies, are characterized by the accumulation of aggregated tau in a variety of brain regions. While tau normally plays an important role in stabilizing the microtubule network of the cytoskeleton, its dissociation from microtubules and eventual aggregation into pathological deposits is an area of intense focus for therapeutic development. Here we discuss the known cellular factors that affect tau aggregation, from post-translational modifications to molecular chaperones. PMID:25666877

  9. Connecting the Dots Between Tau Dysfunction and Neurodegeneration

    PubMed Central

    Frost, Bess; Götz, Jürgen; Feany, Mel B.

    2014-01-01

    Tauopathies are devastating and ultimately fatal neurodegenerative diseases, which are histopathologically defined by insoluble filamentous deposits of abnormally phosphorylated tau protein within neurons and glia. Identifying the causes of abnormal tau phosphorylation and subsequent aggregation has been the focus of much research, and is currently a major target for the development of therapeutic interventions for tauopathies, including Alzheimer’s disease. Recently much has been learned about the sequence of events that lead from tau dysfunction to neuronal death. This review focuses on the cascade of events that are catalyzed by pathological tau, and highlights current and potential therapeutic strategies to target this pathway. PMID:25172552

  10. Lysosomal Dysfunction Promotes Cleavage and Neurotoxicity of Tau In Vivo

    PubMed Central

    Sharp, Katherine A.; Loewen, Carin A.; Mulkearns, Erin; Tyynelä, Jaana; Scherzer, Clemens R.; Feany, Mel B.

    2010-01-01

    Expansion of the lysosomal system, including cathepsin D upregulation, is an early and prominent finding in Alzheimer's disease brain. Cell culture studies, however, have provided differing perspectives on the lysosomal connection to Alzheimer's disease, including both protective and detrimental influences. We sought to clarify and molecularly define the connection in vivo in a genetically tractable model organism. Cathepsin D is upregulated with age in a Drosophila model of Alzheimer's disease and related tauopathies. Genetic analysis reveals that cathepsin D plays a neuroprotective role because genetic ablation of cathepsin D markedly potentiates tau-induced neurotoxicity. Further, generation of a C-terminally truncated form of tau found in Alzheimer's disease patients is significantly increased in the absence of cathepsin D. We show that truncated tau has markedly increased neurotoxicity, while solubility of truncated tau is decreased. Importantly, the toxicity of truncated tau is not affected by removal of cathepsin D, providing genetic evidence that modulation of neurotoxicity by cathepsin D is mediated through C-terminal cleavage of tau. We demonstrate that removing cathepsin D in adult postmitotic neurons leads to aberrant lysosomal expansion and caspase activation in vivo, suggesting a mechanism for C-terminal truncation of tau. We also demonstrate that both cathepsin D knockout mice and cathepsin D–deficient sheep show abnormal C-terminal truncation of tau and accompanying caspase activation. Thus, caspase cleavage of tau may be a molecular mechanism through which lysosomal dysfunction and neurodegeneration are causally linked in Alzheimer's disease. PMID:20664788

  11. Hyperphosphorylated Tau is Elevated in Alzheimer's Disease with Psychosis

    PubMed Central

    Murray, Patrick S.; Kirkwood, Caitlin M.; Gray, Megan C.; Fish, Kenneth N.; Ikonomovic, Milos D.; Hamilton, Ronald L.; Kofler, Julia K.; Klunk, William E.; Lopez, Oscar L.; Sweet, Robert A.

    2014-01-01

    Psychosis occurs in 40–60% of Alzheimer's disease (AD) subjects, is heritable, and indicates amore rapidly progressive disease phenotype. Neuroimaging and postmortem evidence support an exaggerated prefrontal cortical synaptic deficit in AD with psychosis. Microtubule-associated protein tau is a key mediator of amyloid-β-induced synaptotoxicity in AD, and differential mechanisms of progressive intraneuronal phospho-tau accumulation and interneuronal spread of tau aggregates have recently been described. We hypothesized that psychosis in AD would be associated with greater intraneuronal concentration of phospho-tau and greater spread of tau aggregates in prefrontal cortex. We therefore evaluated prefrontal cortex phospho-tau in a cohort of 45 AD cases with and without psychosis. Intraneuronal phospho-tau concentration was higher in subjects with psychosis, while a measure of phospho-tau spread, volume fraction, was not. Across groups both measures were associated with lower scores on the Mini-Mental State Examination and Digit Span Backwards test. These novel findings indicate that tau phosphorylation may be accelerated in AD with psychosis, indicating a more dynamic, exaggerated pathology in AD with psychosis. PMID:24270207

  12. NMR Meets Tau: Insights into Its Function and Pathology

    PubMed Central

    Lippens, Guy; Landrieu, Isabelle; Smet, Caroline; Huvent, Isabelle; Gandhi, Neha S.; Gigant, Benoît; Despres, Clément; Qi, Haoling; Lopez, Juan

    2016-01-01

    In this review, we focus on what we have learned from Nuclear Magnetic Resonance (NMR) studies on the neuronal microtubule-associated protein Tau. We consider both the mechanistic details of Tau: the tubulin relationship and its aggregation process. Phosphorylation of Tau is intimately linked to both aspects. NMR spectroscopy has depicted accurate phosphorylation patterns by different kinases, and its non-destructive character has allowed functional assays with the same samples. Finally, we will discuss other post-translational modifications of Tau and its interaction with other cellular factors in relationship to its (dys)function. PMID:27338491

  13. Updated measurement of the tau lifetime at SLD

    SciTech Connect

    1996-07-23

    We present an updated measurement of the tau lifetime at SLD. 4316 {tau}-pair events, selected from a 150k Z{sup 0} data sample, are analyzed using three techniques: decay length, impact parameter, and impact parameter difference methods. The measurement benefits from the small and stable interaction region at the SLC and the precision CCD pixel vertex detector of the SLD. The combined result is: {tau}{sub {tau}} = 288.1 {+-} 6.1(stat) {+-} 3.3(syst) fs.

  14. Aluminum induces tau aggregation in vitro but not in vivo.

    PubMed

    Mizoroki, Tatsuya; Meshitsuka, Shunsuke; Maeda, Sumihiro; Murayama, Miyuki; Sahara, Naruhiko; Takashima, Akihiko

    2007-07-01

    Etiological studies suggest that aluminum (Al) intake might increase an individual's risk of developing Alzheimer's disease (AD). Biochemical analysis data on the effects of Al, however, are inconsistent. Hence, the pathological involvement of Al in AD remains unclear. If Al is involved in AD, then it is reasonable to hypothesize that Al might be involved in the formation of either amyloid plaques or neurofibrillary tangles (NFTs). Here, we investigated whether Al might be involved in NFT formation by using an in vitro tau aggregation paradigm, a tau-overexpressing neuronal cell line (N2a), and a tau-overexpressing mouse model. Although Al induced tau aggregation in a heparin-induced tau assembly assay, these aggregates were neither thioflavin T positive nor did they resemble tau fibrils seen in human AD brains. With cell lysates from stable cell lines overexpressing tau, the accumulation of SDS-insoluble tau increased when the lysates were treated with at least 100 muM Al-maltolate. Yet Al-maltolate caused illness or death in transgenic mice overexpressing human tau and in non-transgenic littermates well before the Al concentration in the brain reached 100 muM. These results indicate that Al has no direct link to AD pathology.

  15. Evaluation of chromatic cues for trapping Bactrocera tau.

    PubMed

    Li, Lei; Ma, Huabo; Niu, Liming; Han, Dongyin; Zhang, Fangping; Chen, Junyu; Fu, Yueguan

    2017-01-01

    Trapping technology based on chromatic cues is an important strategy in controlling Tephritidae (fruit flies). The objectives of this present study were to evaluate the preference of Bactrocera tau for different chromatic cues, and to explore an easy method to print and reproduce coloured paper. Chromatic cues significantly affected the preference of adult B. tau. Wavelengths in the 515-604 nm range were the suitable wavelengths for trapping B. tau. Different-day-old B. tau had different colour preferences. Virtual wavelengths of 595 nm (yellow) and 568 nm (yellowish green) were the optimum wavelengths for trapping 5-7-day-old B. tau and 30-32-day-old B. tau respectively. The trap type and height significantly influenced B. tau attraction efficiency. The number of B. tau on coloured traps hung perpendicular to plant rows was not significantly higher than the number on traps hung parallel to plant rows. The quantisation of colour on the basis of Bruton's wavelength to RGB function can serve as an alternative method for printing and reproducing coloured paper, but a corrected equation should be established between the theoretical wavelength and actual wavelength of coloured paper. Results show that a compound paper coloured yellow (595 nm) and yellowish green (568 nm) installed at 60 and 90 cm above the ground shows the maximum effect for trapping B. tau. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  16. Early Earth

    NASA Astrophysics Data System (ADS)

    Brown, M.

    2015-05-01

    Earth has continents, subduction and mobile lid plate tectonics, but details of the early evolution are poorly understood. Here I summarize the Hadean-Archean record, review evidence for a hotter Earth and consider geodynamic models for early Earth.

  17. Distribution of animal drugs between skim milk and milk fat fractions in spiked whole milk: Understanding the potential impact on commercial milk products

    USDA-ARS?s Scientific Manuscript database

    Seven animal drugs [penicillin G (PENG), sulfadimethoxine (SDMX), oxytetracycline (OTET), erythromycin (ERY), ketoprofen (KETO), thiabendazole (THIA) and ivermectin (IVR)] were used to evaluate drug distribution between milk fat and skim milk fractions of cow milk. Greater than 90% of radioactivity...

  18. Stabilization of Microtubule-Unbound Tau via Tau Phosphorylation at Ser262/356 by Par-1/MARK Contributes to Augmentation of AD-Related Phosphorylation and Aβ42-Induced Tau Toxicity

    PubMed Central

    Ando, Kanae; Maruko-Otake, Akiko; Ohtake, Yosuke; Hayashishita, Motoki; Sekiya, Michiko; Iijima, Koichi M.

    2016-01-01

    Abnormal accumulation of the microtubule-interacting protein tau is associated with neurodegenerative diseases including Alzheimer’s disease (AD). β-amyloid (Aβ) lies upstream of abnormal tau behavior, including detachment from microtubules, phosphorylation at several disease-specific sites, and self-aggregation into toxic tau species in AD brains. To prevent the cascade of events leading to neurodegeneration in AD, it is essential to elucidate the mechanisms underlying the initial events of tau mismetabolism. Currently, however, these mechanisms remain unclear. In this study, using transgenic Drosophila co-expressing human tau and Aβ, we found that tau phosphorylation at AD-related Ser262/356 stabilized microtubule-unbound tau in the early phase of tau mismetabolism, leading to neurodegeneration. Aβ increased the level of tau detached from microtubules, independent of the phosphorylation status at GSK3-targeted SP/TP sites. Such mislocalized tau proteins, especially the less phosphorylated species, were stabilized by phosphorylation at Ser262/356 via PAR-1/MARK. Levels of Ser262 phosphorylation were increased by Aβ42, and blocking this stabilization of tau suppressed Aβ42-mediated augmentation of tau toxicity and an increase in the levels of tau phosphorylation at the SP/TP site Thr231, suggesting that this process may be involved in AD pathogenesis. In contrast to PAR-1/MARK, blocking tau phosphorylation at SP/TP sites by knockdown of Sgg/GSK3 did not reduce tau levels, suppress tau mislocalization to the cytosol, or diminish Aβ-mediated augmentation of tau toxicity. These results suggest that stabilization of microtubule-unbound tau by phosphorylation at Ser262/356 via the PAR-1/MARK may act in the initial steps of tau mismetabolism in AD pathogenesis, and that such tau species may represent a potential therapeutic target for AD. PMID:27023670

  19. Properties and stability of oil-in-water emulsions stabilized by coconut skim milk proteins.

    PubMed

    Onsaard, Ekasit; Vittayanont, Manee; Srigam, Sukoncheun; McClements, D Julian

    2005-07-13

    Protein fractions were isolated from coconut: coconut skim milk protein isolate (CSPI) and coconut skim milk protein concentrate (CSPC). The ability of these proteins to form and stabilize oil-in-water emulsions was compared with that of whey protein isolate (WPI). The solubility of the proteins in CSPI, CSPC, and WPI was determined in aqueous solutions containing 0, 100, and 200 mM NaCl from pH 3 to 8. In the absence of salt, the minimum protein solubility occurred between pH 4 and 5 for CSPI and CSPC and around pH 5 for WPI. In the presence of salt (100 and 200 mM NaCl), all proteins had a higher solubility than in distilled water. Corn oil-in-water emulsions (10 wt %) with relatively small droplet diameters (d32 approximately 0.46, 1.0, and 0.5 mum for CSPI, CSPC, and WPI, respectively) could be produced using 0.2 wt % protein fraction. Emulsions were prepared with different pH values (3-8), salt concentrations (0-500 mM NaCl), and thermal treatments (30-90 degrees C for 30 min), and the mean particle diameter, particle size distribution, zeta-potential, and creaming stability were measured. Considerable droplet flocculation occurred in the emulsions near the isoelectric point of the proteins: CSPI, pH approximately 4.0; CSPC, pH approximately 4.5; WPI, pH approximately 4.8. Emulsions with monomodal particle size distributions, small mean droplet diameters, and good creaming stability could be produced at pH 7 for CSPI and WPI, whereas CSPC produced bimodal distributions. The CSPI and WPI emulsions remained relatively stable to droplet aggregation and creaming at NaCl concentrations of < or =50 and < or =100 mM, respectively. In the absence salt, the CSPI and WPI emulsions were also stable to thermal treatments at < or =80 and < or =90 degrees C for 30 min, respectively. These results suggest that CSPI may be suitable for use as an emulsifier in the food industry.

  20. Dynamics of skimming flow in the wake of a vegetation patch

    NASA Astrophysics Data System (ADS)

    Mayaud, Jerome R.; Wiggs, Giles F. S.; Bailey, Richard M.

    2016-09-01

    Dryland vegetation is often spatially patchy, and so affects wind flow in complex ways. Theoretical models and wind tunnel testing have shown that skimming flow develops above vegetation patches at high plant densities, resulting in little or no wind erosion in these zones. Understanding the dynamics of skimming flow is therefore important for predicting sediment transport and bedform development in dryland areas. However, no field-based data are available describing turbulent airflow dynamics in the wake of vegetation patches. In this study, turbulent wind flow was examined using high-frequency (10 Hz) sonic anemometry at four measurement heights (0.30 m, 0.55 m, 1.10 m and 1.65 m) along a transect in the lee of an extensive patch of shrubs (z = 1.10 m height) in Namibia. Spatial variations in mean wind velocity, horizontal Reynolds stresses and coherent turbulent structures were analysed. We found that wind velocity in the wake of the patch effectively recovered over ∼12 patch heights (h) downwind, which is 2-5 h longer than previously reported recovery lengths for individual vegetation elements and two-dimensional wind fences. This longer recovery can be attributed to a lack of flow moving around the obstacle in the patch case. The step-change in roughness between the patch canopy and the bare surface in its wake resulted in an initial peak in resultant horizontal shear stress (τr) followed by significant decrease downwind. In contrast to τr , horizontal normal Reynolds stress (u‧2 ‾) progressively increased along the patch wake. A separation of the upper shear layer at the leeside edge of the patch was observed, and a convergence of τr curves implies the formation of a constant stress layer by ∼20 h downwind. The use of τr at multiple heights is found to be a useful tool for identifying flow equilibration in complex aerodynamic regimes. Quadrant analysis revealed elevated frequencies of Q2 (ejection) and Q4 (sweep) events in the immediate lee of the

  1. Effect of skim milk treated with high hydrostatic pressure on permeate flux and fouling during ultrafiltration.

    PubMed

    Leu, Mathilde; Marciniak, Alice; Chamberland, Julien; Pouliot, Yves; Bazinet, Laurent; Doyen, Alain

    2017-09-01

    Ultrafiltration (UF) is largely used in the dairy industry to generate milk and whey protein concentrate for standardization of milk or production of dairy ingredients. Recently, it was demonstrated that high hydrostatic pressure (HHP) extended the shelf life of milk and improved rennet coagulation and cheese yield. Pressurization also modified casein micelle size distribution and promoted aggregation of whey proteins. These changes are likely to affect UF performance. Consequently, this study determined the effect of skim milk pressurization (300 and 600 MPa, 5 min) on UF performance in terms of permeate flux decline and fouling. The effect of HHP on milk proteins was first studied and UF was performed in total recycle mode at different transmembrane pressures to determine optimal UF operational parameters and to evaluate the effect of pressurization on critical and limiting fluxes. Ultrafiltration was also performed in concentration mode at a transmembrane pressure of 345 kPa for 130 or 140 min to evaluate the decline of permeate flux and to determine fouling resistances. It was observed that average casein micelle size decreased by 32 and 38%, whereas β-lactoglobulin denaturation reached 30 and 70% at 300 and 600 MPa, respectively. These results were directly related to UF performance because initial permeate fluxes in total recycle mode decreased by 25% at 300 and 600 MPa compared with nonpressurized milk, critical flux, and limiting flux, which were lower during UF of milk treated with HHP. During UF in concentration mode, initial permeate fluxes were 30% lower at 300 and 600 MPa compared with the control, but the total flux decline was higher for nonpressurized milk (62%) compared with pressure-treated milk (30%). Fouling resistances were similar, whatever the treatment, except at 600 MPa where irreversible fouling was higher. Characterization of the fouling layer showed that caseins and β-lactoglobulin were mainly involved in membrane fouling after UF of

  2. Effect of ceramic membrane channel diameter on limiting retentate protein concentration during skim milk microfiltration.

    PubMed

    Adams, Michael C; Barbano, David M

    2016-01-01

    Our objective was to determine the effect of retentate flow channel diameter (4 or 6mm) of nongraded permeability 100-nm pore size ceramic membranes operated in nonuniform transmembrane pressure mode on the limiting retentate protein concentration (LRPC) while microfiltering (MF) skim milk at a temperature of 50°C, a flux of 55 kg · m(-2) · h(-1), and an average cross-flow velocity of 7 m · s(-1). At the above conditions, the retentate true protein concentration was incrementally increased from 7 to 11.5%. When temperature, flux, and average cross-flow velocity were controlled, ceramic membrane retentate flow channel diameter did not affect the LRPC. This indicates that LRPC is not a function of the Reynolds number. Computational fluid dynamics data, which indicated that both membranes had similar radial velocity profiles within their retentate flow channels, supported this finding. Membranes with 6-mm flow channels can be operated at a lower pressure decrease from membrane inlet to membrane outlet (ΔP) or at a higher cross-flow velocity, depending on which is controlled, than membranes with 4-mm flow channels. This implies that 6-mm membranes could achieve a higher LRPC than 4-mm membranes at the same ΔP due to an increase in cross-flow velocity. In theory, the higher LRPC of the 6-mm membranes could facilitate 95% serum protein removal in 2 MF stages with diafiltration between stages if no serum protein were rejected by the membrane. At the same flux, retentate protein concentration, and average cross-flow velocity, 4-mm membranes require 21% more energy to remove a given amount of permeate than 6-mm membranes, despite the lower surface area of the 6-mm membranes. Equations to predict skim milk MF retentate viscosity as a function of protein concentration and temperature are provided. Retentate viscosity, retentate recirculation pump frequency required to maintain a given cross-flow velocity at a given retentate viscosity, and retentate protein

  3. Bovine chromosomal regions affecting rheological traits in rennet-induced skim milk gels.

    PubMed

    Gregersen, V R; Gustavsson, F; Glantz, M; Christensen, O F; Stålhammar, H; Andrén, A; Lindmark-Månsson, H; Poulsen, N A; Larsen, L B; Paulsson, M; Bendixen, C

    2015-02-01

    Optimizing cheese yield and quality is of central importance to cheese manufacturing. The yield is associated with the time it takes before the gel has an optimal consistency for further processing, and it is well known that gel formation differs between individual milk samples. By identifying genomic regions affecting traits related to rennet-induced gelation, the aim of this study was to identify potential candidate genes affecting these traits. Hence, rennet-induced gelation, including rennet coagulation time, gel strength, and yield stress, was measured in skim milk samples collected from 379 animals of the Swedish Red breed using low-amplitude oscillation measurements. All animals had genotypes for almost 621,000 segregating single nucleotide polymorphisms (SNP), identified using the Bovine HD SNPChip (Illumina Inc., San Diego, CA). The genome was scanned for associations, haplotypes based on SNP sets comprising highly associated SNP were inferred, and the effects of the 2 most common haplotypes within each region were analyzed using mixed models. Even though the number of animals was relatively small, a total of 21 regions were identified, with 4 regions showing association with more than one trait. A major quantitative trait locus for all traits was identified around the casein cluster explaining between 9.3 to 15.2% of the phenotypic variation of the different traits. In addition, 3 other possible candidate genes were identified; that is, UDP-N-acetyl-α-d-galactosamine:polypeptide N-acetylgalactosaminyl-transferase 1 (GALNT1), playing a role in O-glycosylation of κ-casein, and 2 cathepsins, CTSZ and CTSC, possibly involved in proteolysis of milk proteins. We have shown that other genes than the casein genes themselves may be involved in the regulation of gelation traits. However, additional analysis is needed to confirm these results. To our knowledge, this is the first study identifying quantitative trait loci affecting rennet-induced gelation of skim

  4. Discoveries of tau, abnormally hyperphosphorylated tau and others of neurofibrillary degeneration: a personal historical perspective.

    PubMed

    Iqbal, Khalid; Grundke-Iqbal, Inge

    2006-01-01

    Alzheimer disease was described by Alois Alzheimer in 1907, but it was not until approximately 60-70 years later that any new significant developments were reported on the pathology of this disease. The discoveries that laid down the foundation for the exciting research that has been carried out during the last approximately 20 years and that have significantly enhanced our understanding of the disease are the ultrastructure of neurofibrillary tangles and neuritic (senile) plaques, the clinical-pathological correlation of these lesions to the presence of dementia, and the bulk isolation and protein composition of paired helical filaments and plaque amyloid. We discovered tau as the major protein subunit of paired helical filaments/neurofibrillary tangles, the abnormal hyperphosphorylation of this protein in this lesion and in Alzheimer brain cytosol and the gain of toxic function by the cytosolic abnormally hyperphosphorylated tau in Alzheimer brain. Here we present a personal historical account of the work in our laboratories that led, in 1986, to the discoveries of tau and its abnormal hyperphosphorylation in paired helical filaments and Alzheimer brain cytosol. This article also describes several major findings which subsequently resulted from the abnormal hyperphosphorylation of tau and in a large part account for the current understanding of the role of this lesion in Alzheimer disease and other tauopathies.

  5. Constraining new interactions with leptonic {tau} decays

    SciTech Connect

    Pich, A.; Silva, J.P.

    1995-10-01

    The recent measurements of the Michel parameters in {tau} decays enable, for the first time, a thorough analysis of the leptonic sector. In general, in models beyond the standard model, these parameters will be altered through changes in the {ital W} and {ital Z} couplings, and/or through interactions mediated by new gauge bosons. We perform a complete, model-independent analysis of the constraints imposed by the present data on such boson-mediated interactions, and point out the existence of useful relations among the couplings.

  6. A measurement of the tau mass

    NASA Astrophysics Data System (ADS)

    Albrecht, H.; Ehrlichmann, H.; Hamacher, T.; Hofmann, R. P.; Kirchhoff, T.; Nau, A.; Nowak, S.; Schröder, H.; Schulz, H. D.; Walter, M.; Wurth, R.; Appuhn, R. D.; Hast, C.; Kolanoski, H.; Lange, A.; Lindner, A.; Mankel, R.; Schieber, M.; Siegmund, T.; Spaan, B.; Thurn, H.; Töpfer, D.; Walther, A.; Wegener, D.; Paulini, M.; Reim, K.; Wegener, H.; Mundt, R.; Oest, T.; Reiner, R.; Schmidt-Parzefall, W.; Funk, W.; Stiewe, J.; Werner, S.; Ehret, K.; Hofmann, W.; Hüpper, A.; Khan, S.; Knöpfle, K. T.; Spengler, J.; Britton, D. I.; Charlesworth, C. E. K.; Edwards, K. W.; Hyatt, E. R. F.; Kapitza, H.; Krieger, P.; Patel, P. M.; Prentice, J. D.; Saull, P. R. B.; Tzamariudaki, K.; van de Water, R. G.; Yoon, T.-S.; Reβing, D.; Schmidtler, M.; Schneider, M.; Schubert, K. R.; Strahl, K.; Waldi, R.; Weseler, S.; Kernel, G.; Križan, P.; Križnič, E.; Podobnik, T.; Živko, T.; Cronström, H. I.; Jönsson, L.; Balagura, V.; Belyaev, I.; Danilov, M.; Droutskoy, A.; Golutvin, A.; Gorelov, I.; Kostina, G.; Lubimov, V.; Murat, P.; Pakhlov, P.; Ratnikov, F.; Semenov, S.; Shibaev, V.; Soloshenko, V.; Tichomirov, I.; Zaitsev, Yu.; Argus Collaboration

    1992-10-01

    Using the ARGUS detector at the DORIS II storage ring, a new measurement of the mass of the τ lepton has been obtained. An analysis of the tau pseudomass spectrum for decays of the type τ- → π-π-π+ντ finds mτ = 1776.3±2.4±1.4 MeV/ c2. This result also leads to an improvement of the upper limit on the ντ mass to mντ < 31 MeV/ c2 at the 95% confidence level.

  7. NEW LIMITS FOR NEUTRINOLESS TAU DECAYS

    SciTech Connect

    Jessop, Colin P.

    2003-05-01

    Neutrinoless 3-prong tau lepton decays into a charged lepton and either two all channels the numbers of events found are compatible with background an update of a previous study and the addition of six decay channels. In charged particles or one neutral meson have been searched for using 4.79 fb{sup -1} estimates and branching fraction upper limits are set for 28 different decay modes. These limits are either more stringent than those set previously or of data collected with the CLEO II detector at CESR. This analysis represents represent the first attempt to find these decays.

  8. Phosphorylation of Tau at S422 is enhanced by Abeta in TauPS2APP triple transgenic mice.

    PubMed

    Grueninger, Fiona; Bohrmann, Bernd; Czech, Christian; Ballard, Theresa Maria; Frey, Johann R; Weidensteiner, Claudia; von Kienlin, Markus; Ozmen, Laurence

    2010-02-01

    Amyloid beta peptides and microtubule-associated protein Tau are misfolded and form aggregates in brains of Alzheimer's disease patients. To examine their specific roles in the pathogenesis of Alzheimer's disease and their relevance in neurodegenerative processes, we have created TauPS2APP triple transgenic mice that express human mutated Amyloid Precursor Protein, presenilin 2 and Tau. We present a cross-sectional analysis of these mice at 4, 8, 12 and 16 months of age. By comparing with single transgenic Tau mice, we demonstrate that accumulation of Abeta in TauPS2APP triple transgenic mice impacts on Tau pathology by increasing the phosphorylation of Tau at serine 422, as determined by a novel immunodetection method that is able to reliably measure phospho-Tau species in transgenic mouse brains. The TauPS2APP triple transgenic mouse model will be very useful for studying the effect of new therapeutic paradigms on amyloid deposition and downstream neurofibrillary tangle development.

  9. 18F-AV-1451 tau PET imaging correlates strongly with tau neuropathology in MAPT mutation carriers.

    PubMed

    Smith, Ruben; Puschmann, Andreas; Schöll, Michael; Ohlsson, Tomas; van Swieten, John; Honer, Michael; Englund, Elisabet; Hansson, Oskar

    2016-09-01

    Tau positron emission tomography ligands provide the novel possibility to image tau pathology in vivo However, little is known about how in vivo brain uptake of tau positron emission tomography ligands relates to tau aggregates observed post-mortem. We performed tau positron emission tomography imaging with (18)F-AV-1451 in three patients harbouring a p.R406W mutation in the MAPT gene, encoding tau. This mutation results in 3- and 4-repeat tau aggregates similar to those in Alzheimer's disease, and many of the mutation carriers initially suffer from memory impairment and temporal lobe atrophy. Two patients with short disease duration and isolated memory impairment exhibited (18)F-AV-1451 uptake mainly in the hippocampus and adjacent temporal lobe regions, correlating with glucose hypometabolism in corresponding regions. One patient died after 26 years of disease duration with dementia and behavioural deficits. Pre-mortem, there was (18)F-AV-1451 uptake in the temporal and frontal lobes, as well as in the basal ganglia, which strongly correlated with the regional extent and amount of tau pathology in post-mortem brain sections. Amyloid-β ((18)F-flutemetamol) positron emission tomography scans were negative in all cases, as were stainings of brain sections for amyloid. This provides strong evidence that (18)F-AV-1451 positron emission tomography can be used to accurately quantify in vivo the regional distribution of hyperphosphorylated tau protein.

  10. 18F-AV-1451 tau PET imaging correlates strongly with tau neuropathology in MAPT mutation carriers

    PubMed Central

    Puschmann, Andreas; Schöll, Michael; Ohlsson, Tomas; van Swieten, John; Honer, Michael; Englund, Elisabet

    2016-01-01

    Tau positron emission tomography ligands provide the novel possibility to image tau pathology in vivo. However, little is known about how in vivo brain uptake of tau positron emission tomography ligands relates to tau aggregates observed post-mortem. We performed tau positron emission tomography imaging with 18F-AV-1451 in three patients harbouring a p.R406W mutation in the MAPT gene, encoding tau. This mutation results in 3- and 4-repeat tau aggregates similar to those in Alzheimer’s disease, and many of the mutation carriers initially suffer from memory impairment and temporal lobe atrophy. Two patients with short disease duration and isolated memory impairment exhibited 18F-AV-1451 uptake mainly in the hippocampus and adjacent temporal lobe regions, correlating with glucose hypometabolism in corresponding regions. One patient died after 26 years of disease duration with dementia and behavioural deficits. Pre-mortem, there was 18F-AV-1451 uptake in the temporal and frontal lobes, as well as in the basal ganglia, which strongly correlated with the regional extent and amount of tau pathology in post-mortem brain sections. Amyloid-β (18F-flutemetamol) positron emission tomography scans were negative in all cases, as were stainings of brain sections for amyloid. This provides strong evidence that 18F-AV-1451 positron emission tomography can be used to accurately quantify in vivo the regional distribution of hyperphosphorylated tau protein. PMID:27357347

  11. INVESTIGATING PLANET FORMATION IN CIRCUMSTELLAR DISKS: CARMA OBSERVATIONS OF RY Tau AND DG Tau

    SciTech Connect

    Isella, Andrea; Carpenter, John M.; Sargent, Anneila I.

    2010-05-10

    We present CARMA observations of the thermal dust emission from the circumstellar disks around the young stars RY Tau and DG Tau at wavelengths of 1.3 mm and 2.8 mm. The angular resolution of the maps is as high as 0.''15, or 20 AU at the distance of the Taurus cloud, which is a factor of 2 higher than has been achieved to date at these wavelengths. The unprecedented detail of the resulting disk images enables us to address three important questions related to the formation of planets. (1) What is the radial distribution of the circumstellar dust? (2) Does the dust emission show any indication of gaps that might signify the presence of (proto-)planets? (3) Do the dust properties depend on the orbital radius? We find that modeling the disk surface density in terms of either a classical power law or the similarity solution for viscous disk evolution reproduces the observations well. Both models constrain the surface density between 15 and 50 AU to within 30% for a given dust opacity. Outside this range, the densities inferred from the two models differ by almost an order of magnitude. The 1.3 mm image from RY Tau shows two peaks separated by 0.''2 with a decline in the dust emission toward the stellar position, which is significant at about 2{sigma}-4{sigma}. For both RY Tau and DG Tau, the dust emission at radii larger than 15 AU displays no significant deviation from an unperturbed viscous disk model. In particular, no radial gaps in the dust distribution are detected. Under reasonable assumptions, we exclude the presence of planets more massive than 5 M{sub J} orbiting either star at distances between about 10 and 60 AU, unless such a planet is so young that there has been insufficient time to open a gap in the disk surface density. The radial variation of the dust opacity slope, {beta}, was investigated by comparing the 1.3 mm and 2.8 mm observations. We find mean values of {beta} of 0.5 and 0.7 for DG Tau and RY Tau, respectively. Variations in {beta} are

  12. Molecular Absorption in the Disk of GV Tau

    NASA Astrophysics Data System (ADS)

    Carr, John

    High resolution MIR spectroscopy with SOFIA offers the opportunity for unique insights into the chemical evolution of disks (e.g., the origin of prebiotic molecules) and planet formation processes. We propose to use EXES to measure molecular absorption in the edge-on protoplanetary disk of GV Tau N. The proposed observations will search for and characterize several molecules of astrobiological importance: water, formaldehyde (H2CO), and formic acid (HCOOH). The latter two simple molecules are potential chemical starting points for the synthesis of sugars, amino acids, and RNA. We will also search for SO2, which may be the dominant gas phase carrier of sulfur in disk atmospheres. Our observations will constrain the (poorly known) degree of sulfur depletion in disks, which bears on our understanding of the differentiation of the Earth's core. With the exception of water, little to nothing is known about these molecules in inner protoplanetary disks. Molecular column densities and relative abundances will be determined for comparison with chemical disk models and abundances in comets and the interstellar medium. In addition to lending new insights into the chemical evolution in the planet formation regions of protoplanetary disks, the observations will also serve as valuable pathfinder observations for JWST.

  13. Mobility and subcellular localization of endogenous, gene-edited Tau differs from that of over-expressed human wild-type and P301L mutant Tau

    PubMed Central

    Di Xia; Gutmann, Julia M.; Götz, Jürgen

    2016-01-01

    Alzheimer’s disease (AD) and a subset of frontotemporal dementia termed FTLD-Tau are characterized by a massive, yet incompletely characterized and understood redistribution of Tau. To establish a framework for understanding this pathology, we used the genome-editing tool TALEN and generated Tau-mEOS2 knock-in mice to determine the mobility and subcellular localization of endogenous Tau in hippocampal cultures. We analysed Tau in axons, dendrites and spines at three stages of maturation using live-cell imaging, photo-conversion and FRAP assays. Tau-mEOS2 cultures were compared with those over-expressing EGFP-tagged forms of human wild-type (hWT-Tau) and P301L mutant Tau (hP301L-Tau), modelling Tau accumulation in AD and FTLD-Tau, respectively. In developing neurons, Tau-mEOS2 followed a proximo-distal gradient in axons and a subcellular distribution similar to that of endogenous Tau in neurons obtained from wild-type mice, which were abolished, when either hWT-Tau or hP301L-Tau was over-expressed. For the three conditions, FRAP analysis revealed a similar mobility in dendrites compared with axons; however, Tau-mEOS2 was less mobile than hWT-Tau and hP301L-Tau and the mobile fraction was smaller, possibly reflecting less efficient microtubule binding of Tau when over-expressed. Together, our study presents Tau-mEOS2 mice as a novel tool for the study of Tau in a physiological and a pathological context. PMID:27378256

  14. Tau-REx: A new look at the retrieval of exoplanetary atmospheres

    NASA Astrophysics Data System (ADS)

    Waldmann, Ingo

    2014-11-01

    The field of exoplanetary spectroscopy is as fast moving as it is new. With an increasing amount of space and ground based instruments obtaining data on a large set of extrasolar planets we are indeed entering the era of exoplanetary characterisation. Permanently at the edge of instrument feasibility, it is as important as it is difficult to find the most optimal and objective methodologies to analysing and interpreting current data. This is particularly true for smaller and fainter Earth and Super-Earth type planets.For low to mid signal to noise (SNR) observations, we are prone to two sources of biases: 1) Prior selection in the data reduction and analysis; 2) Prior constraints on the spectral retrieval. In Waldmann et al. (2013), Morello et al. (2014) and Waldmann (2012, 2014) we have shown a prior-free approach to data analysis based on non-parametric machine learning techniques. Following these approaches we will present a new take on the spectral retrieval of extrasolar planets. Tau-REx (tau-retrieval of exoplanets) is a new line-by-line, atmospheric retrieval framework. In the past the decision on what opacity sources go into an atmospheric model were usually user defined. Manual input can lead to model biases and poor convergence of the atmospheric model to the data. In Tau-REx we have set out to solve this. Through custom built pattern recognition software, Tau-REx is able to rapidly identify the most likely atmospheric opacities from a large number of possible absorbers/emitters (ExoMol or HiTran data bases) and non-parametrically constrain the prior space for the Bayesian retrieval. Unlike other (MCMC based) techniques, Tau-REx is able to fully integrate high-dimensional log-likelihood spaces and to calculate the full Bayesian Evidence of the atmospheric models. We achieve this through a combination of Nested Sampling and a high degree of code parallelisation. This allows for an exact and unbiased Bayesian model selection and a fully mapping of potential

  15. Effects of High-Pressure, Microbial Transglutaminase and Glucono-δ-Lactone on the Aggregation Properties of Skim Milk

    PubMed Central

    Lee, Sang Yoon; Choi, Mi-Jung; Cho, Hyung-Yong

    2016-01-01

    The object in this study is to investigate the effects of high pressure and freezing processes on the curdling of skim milk depending on the presence of transglutaminase (TGase) and glucono-δ-lactone (GdL). Skim milk was treated with atmospheric freezing (AF), high pressure (HP), pressure-shift freezing (PSF) and high pressure sub-zero temperature (HPST) processing conditions. After freezing and pressure processing, these processed milk samples were treated with curdling agents, such as TGase and GdL. Pressurized samples (HP, PSF and HPST) had lower lightness than that of the control. In particular, PSF had the lowest lightness (p<0.05). Likewise, the PSF proteins were the most insoluble regardless of whether they were activated by TGase and GdL, indicating the highest rate of protein aggregation (p<0.05). Furthermore, the TGase/GdL reaction resulted in thick bands corresponding to masses larger than 69 kDa, indicating curdling. Casein bands were the weakest in PSF-treated milk, revealing that casein was prone to protein aggregation. PSF also had the highest G' value among all treatments after activation by TGase, implying that PSF formed the hardest curd. However, adding GdL decreased the G' values of the samples except HPST-treated samples. Synthetically, the PSF process was advantageous for curdling of skim milk. PMID:27433104

  16. Application of a dye-binding method for the determination of available lysine in skim milk powders.

    PubMed

    Aalaei, Kataneh; Rayner, Marilyn; Tareke, Eden; Sjöholm, Ingegerd

    2016-04-01

    A dye-binding method using Acid Orange 12 was investigated regarding its suitability for the quantification of available lysine, as a means of monitoring the Maillard reaction in skim milk powders. The method was evaluated by analyzing a wide range of milk powders produced by three different drying methods and stored under various conditions. A pilot-scale freeze-dryer, spray-dryer and drum-dryer were used to produce skim milk powders and the samples were stored at two temperatures (20 °C and 30 °C) and two relative humidities (33% and 52%) under strictly controlled conditions. Moreover to validate the method, two protein isolates; bovine serum albumin and casein were investigated for their available lysine content. The results demonstrate the suitability of this method for measuring the available lysine in skim milk powders with good precision and high reproducibility. The relative standard deviations obtained from the 125 freeze-dried powders were 1.8%, and those from the 100 drum-dried samples were all 1.9%. The highest variation was found for the spray-dried powders, which showed relative standard deviations between 0.9% and 6.7%. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Microfiltration of skim milk and modified skim milk using a 0.1-µm ceramic uniform transmembrane pressure system at temperatures of 50, 55, 60, and 65°C.

    PubMed

    Hurt, E E; Adams, M C; Barbano, D M

    2015-02-01

    Increasing the temperature of microfiltration (MF) to >50°C may allow for operation at higher fluxes and reduce the bacterial growth during MF. However, there is a concern that operating at higher temperatures could cause calcium phosphate precipitation that would lead to membrane fouling. Our objective was to determine the effect of operating a 0.1-µm ceramic uniform transmembrane pressure MF unit at temperatures of 50, 55, 60, and 65°C on membrane fouling and serum protein (SP) removal from skim milk with and without removal of low-molecular-weight soluble milk components by ultrafiltration (UF) before MF at a flux of 54kg/m(2) per hour. For each replicate, 1,000kg of pasteurized skim milk was split into 2 batches. One batch was ultrafiltered (with diafiltration) to remove an average of 89±2% of the lactose and a percentage of the soluble calcium and phosphorus. The retentate from UF was diluted back to the protein concentration of skim milk, creating the diluted UF retentate (DUR). On subsequent days, both the DUR and skim milk were run on the MF unit with the flux maintained at 54kg/m(2) per hour and a concentration factor of 3× and the system run in recycle mode. The temperature of MF was increased in 5°C steps from 50 to 65°C, with a 1-h stabilization period after each increase. During the run, transmembrane pressure was monitored and permeate and retentate samples were taken and analyzed to determine if any changes in SP, calcium, or phosphorus passage through the membrane occurred. Increasing temperature of MF from 50 to 65°C at a flux of 54kg/m(2) per hour did not produce a large increase in membrane fouling when using either skim milk or a DUR as the MF feed type as measured by changes in transmembrane pressure. Increasing the temperature to 65°C only caused a slight reduction in calcium concentration in the permeate (11±3%) that was similar between the 2MF feed types. Increasing processing temperature reduced the percentage of SP removal by the

  18. Impact of the Skim Milk Powder Manufacturing Process on the Flavor of Model White Chocolate.

    PubMed

    Stewart, Ashleigh; Grandison, Alistair S; Ryan, Angela; Festring, Daniel; Methven, Lisa; Parker, Jane K

    2017-02-15

    Milk powder is an important ingredient in the confectionery industry, but its variable nature has consequences for the quality of the final confectionary product. This paper demonstrates that skim milk powders (SMP) produced using different (but typical) manufacturing processes, when used as ingredients in the manufacture of model white chocolates, had a significant impact on the sensory and volatile profiles of the chocolate. SMP was produced from raw bovine milk using either low or high heat treatment, and a model white chocolate was prepared from each SMP. A directional discrimination test with naïve panelists showed that the chocolate prepared from the high heat SMP had more caramel/fudge character (p < 0.0001), and sensory profiling with an expert panel showed an increase in both fudge (p < 0.05) and condensed milk (p < 0.05) flavor. Gas chromatography (GC)-mass spectrometry and GC-olfactometry of both the SMPs and the model chocolates showed a concomitant increase in Maillard-derived volatiles which are likely to account for this change in flavor.

  19. Thermal Aggregation of Calcium-Fortified Skim Milk Enhances Probiotic Protection during Convective Droplet Drying.

    PubMed

    Wang, Juan; Huang, Song; Fu, Nan; Jeantet, Romain; Chen, Xiao Dong

    2016-08-03

    Probiotic bacteria have been reported to confer benefits on hosts when delivered in an adequate dose. Spray-drying is expected to produce dried and microencapsulated probiotic products due to its low production cost and high energy efficiency. The bottleneck in probiotic application addresses the thermal and dehydration-related inactivation of bacteria during process. A protective drying matrix was designed by modifying skim milk with the principle of calcium-induced protein thermal aggregation. The well-defined single-droplet drying technique was used to monitor the droplet-particle conversion and the protective effect of this modified Ca-aggregated milk on Lactobacillus rhamnosus GG. The Ca-aggregated milk exhibited a higher drying efficiency and superior protection on L. rhamnosus GG during thermal convective drying. The mechanism was explained by the aggregation in milk, causing the lower binding of water in the serum phase and, conversely, local concentrated milk aggregates involved in bacteria entrapment in the course of drying. This work may open new avenues for the development of probiotic products with high bacterial viability and calcium enrichment.

  20. Encapsulation in alginate-skim milk microspheres improves viability of Lactobacillus bulgaricus in stimulated gastrointestinal conditions.

    PubMed

    Pan, Ling-Xia; Fang, Xiu-Juan; Yu, Zhen; Xin, Yang; Liu, Xiao-Ying; Shi, Lu-E; Tang, Zhen-Xing

    2013-05-01

    Lactobacillus delbrueckii subsp. bulgaricus (L. bulgaricus) was encapsulated in alginate-skim milk microspheres. Characteristics of encapsulated L. bulgaricus, such as pH stability, bile stability, storage stability and release property, were studied in this paper. The viability of free L. bulgaricus was not observed after 1 min in simulated gastric fluids (SGF) at pH 2.5 or 2.0. Compared with that of free L. bulgaricus, the viability of encapsulated L. bulgaricus only decreased 0.7 log CFU/g and 2 log CFU/g after 2.0 h incubation in SGF at pH 2.5 and pH 2.0, respectively. L. bulgaricus was also sensitive to bile solution. The viability of free L. bulgaricus was fully lost after 1 h incubation in 1 and 2% bile solution, while the viability of encapsulated L. bulgaricus was only lost 2 log CFU/g and 2.6 log CFU/g in 1 and 2% bile solution at the same time, respectively. Encapsulated L. bulgaricus could be completely released from microspheres in simulated intestinal fluid (pH 6.8) within 2 h. The viability of encapsulated L. bulgaricus retained around 8 log CFU/g when stored at 4°C for 30 days. The current encapsulation technique enables a large proportion of L. bulgaricus to remain good bioactive in a simulated gastrointestinal tract environment.

  1. Comparative study of particle structure evolution during water sorption: skim and whole milk powders.

    PubMed

    Murrieta-Pazos, I; Gaiani, C; Galet, L; Cuq, B; Desobry, S; Scher, J

    2011-10-01

    Surface composition of dairy powders influences significantly a quantity of functional properties such as rehydration, caking, agglomeration. Nevertheless, the kinetic of water uptake by the powders was never directly related to the structure and the composition of the surface. In this work, the effect of relative humidity on the structural reorganization of two types of dairy powder was studied. The water-powder interaction for industrial whole milk powder, and skim milk powder was studied using dynamic vapor sorption. The water sorption isotherms were fitted with a Brunner-Emmet-Teller model and each stage of the sorption curve was analyzed with a Fickian diffusion. The water content in the monolayer predicted for each powder and the moisture diffusivity calculated were discussed and compared. Concurrently, powders microstructure and powders surface under variable relative humidity were assessed by X-ray photoelectron spectroscopy, scanning electron microscopy coupled with energy dispersive X-ray and atomic force microscopy. A correlation between the data obtained from the sorption isotherms and the modifications of structure allowed us to conclude that powder microstructure and chemical state of the components could play an important role in determining the water diffusivity.

  2. Availability of calcium from skim milk, calcium sulfate and calcium carbonate for bone mineralization in pigs.

    PubMed

    Pointillart, A; Coxam, V; Sève, B; Colin, C; Lacroix, C H; Guéguen, L

    2000-01-01

    Dairy products provide abundant, accessible calcium for humans, while some calcium sulfate-rich mineral waters could provide appreciable amounts of calcium. But there is little evidence that this calcium is as available as milk calcium for making bone. The availability of calcium was studied by monitoring bone parameters in 2-month-old pigs fed restricted amounts of calcium (70% RDA) for 2.5 months. The 3 main (> or = 50% Ca intake) Ca sources were either CaCO3 or CaSO4 or skim milk powder (29% of the diet). The bones of the pigs fed the "milk" diet had higher (P < 0.01) ash contents, breaking strength and density (DEXA) than those of the two others groups, in which the bone values were similar. Thus, the calcium provided by a diet containing milk appears to ensure better bone mineralization than do calcium salts included in a non-milk diet. The calcium restriction may have enhanced some milk properties to stimulate calcium absorption in these young, rapidly growing pigs.

  3. The rennet coagulation mechanism of skim milk as observed by transmission diffusing wave spectroscopy.

    PubMed

    Sandra, S; Alexander, Marcela; Dalgleish, Douglas G

    2007-04-15

    The technique of forward-scattering diffusing wave spectroscopy has been used to study the rennet-induced gelation of skim milk. The results allow the comparison of a colloidal suspension at a realistic concentration (Phi approximately 10%) compared with well-established measurements made on highly-diluted milk samples. It is shown that the partially renneted casein micelles do not begin to approach one another until the extent of breakdown of kappa-casein has reached about 70%; above this point, they interact increasingly strongly with the extent of proteolysis. This interaction initially restricts the diffusive motion of the particles rather than causing true aggregation. Only after more extensive removal of the protective kappa-casein does true aggregation occur, with the appearance of a space-filling gel (defined by rheology as having a value of tandelta<1). The results show in greater detail than hitherto the progress of interactions between the particles in a system where the steric stabilization is progressively destroyed, and suggest that the renneting of milk at its normal concentration cannot be described simply by reactions between freely-diffusing particles.

  4. Effect of carrageenan addition on the rennet-induced gelation of skim milk.

    PubMed

    Wang, Fang; Zhang, Wei; Ren, Fazheng

    2016-09-01

    Carrageenan (CG) (κ-CG, ι-CG and λ-CG) was added to skim milk and the rennet-induced aggregation was studied. Caseinomacropeptide (CMP) release, diffusing wave spectroscopy (DWS) and rheology were used to follow the structural dynamics of casein micelles during gelation. The influence of carrageenan on the nature of protein interactions in the gels was investigated using a combination of ultracentrifugation and specific dissociating agents. For the recombined samples containing κ-CG and low concentrations of ι-CG and λ-CG, the CMP release was slowed down; however, the development of DWS and rheological parameters was similar to that of the control sample, and the increase in the incorporation of proteins through calcium bridges and hydrophobic interactions may be the most likely contributors. For the recombined samples containing high concentrations of ι-CG and λ-CG, other factors may impede the gel formation process. High concentrations of ι-CG and λ-CG strongly interfered with the rennet-induced aggregation, interrupted the interaction of caseins and therefore may contribute to good quality of low-fat cheese. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  5. Rennet-induced aggregation of heated pH-adjusted skim milk.

    PubMed

    Anema, Skelte G; Lee, Siew Kim; Klostermeyer, Henning

    2011-08-10

    Heated (20-100 °C/0-30 min) skim milks (pH 6.5-7.1) were diluted in buffer (pH 7.0). Rennet was added, and the particle size with time was measured. For all samples, the size initially decreased (lag phase) and then increased (aggregation phase). Milks heated at ≤60 °C had short lag phases and rapid aggregation phases regardless of pH. Milks heated at >60 °C at pH 6.5 had long lag phases and slow aggregation phases. As the pH increased, the lag phase shortened and the aggregation phase accelerated. The aggregation time was correlated with the level of whey protein associated with the casein micelles and with the level of κ-casein dissociated from the micelles. Heated milks formed weak gels when renneted. It is proposed that the milks heated at low pH have whey proteins associated with the casein micelles and that these denatured whey proteins stabilize the micelles to aggregation by rennet and therefore inhibit gelation. In the milks heated at higher pH, the whey proteins associate with κ-casein in the serum and, on rennet treatment, the κ-casein-depleted micelles and the serum-phase whey protein/κ-casein complexes aggregate; however, the denatured whey proteins stabilize the aggregates so that gelation is still inhibited.

  6. Development and shelf-life determination of pasteurized, microfiltered, lactose hydrolyzed skim milk.

    PubMed

    Antunes, A E C; Silva E Alves, A T; Gallina, D A; Trento, F K H S; Zacarchenco, P B; Van Dender, A G F; Moreno, I; Ormenese, R C S C; Spadoti, L M

    2014-09-01

    The segment of the world population showing permanent or temporary lactose intolerance is quite significant. Because milk is a widely consumed food with an high nutritional value, technological alternatives have been sought to overcome this dilemma. Microfiltration combined with pasteurization can not only extend the shelf life of milk but can also maintain the sensory, functional, and nutritional properties of the product. This studied developed a pasteurized, microfiltered, lactose hydrolyzed (delactosed) skim milk (PMLHSM). Hydrolysis was performed using β-galactosidase at a concentration of 0.4mL/L and incubation for approximately 21h at 10±1°C. During these procedures, the degree of hydrolysis obtained (>90%) was accompanied by evaluation of freezing point depression, and the remaining quantity of lactose was confirmed by HPLC. Milk was processed using a microfiltration pilot unit equipped with uniform transmembrane pressure (UTP) ceramic membranes with a mean pore size of 1.4 μm and UTP of 60 kPa. The product was submitted to physicochemical, microbiological, and sensory evaluations, and its shelf life was estimated. Microfiltration reduced the aerobic mesophilic count by more than 4 log cycles. We were able to produce high-quality PMLHSM with a shelf life of 21 to 27d when stored at 5±1°C in terms of sensory analysis and proteolysis index and a shelf life of 50d in regard to total aerobic mesophile count and titratable acidity.

  7. Electrochemical treatment of skim serum effluent from natural rubber latex centrifuging units.

    PubMed

    Abraham, Vimalamma T; Radhakrishnan Nair, N; Madhu, G

    2009-08-15

    Electrochemical treatment of raw and anaerobically treated skim serum effluent from natural rubber latex centrifuging units was investigated using different electrodes like aluminium, stainless steel, mild steel, and cast iron in the presence of chloride ions. Experimental results were assessed in terms of the removal of COD, biochemical oxygen demand (BOD), TKN, ammoniacal nitrogen, turbidity, sulphides and phosphates. The effect of operating factors such as supporting electrolyte, duration of electrolysis, pH, concentration of effluent and the presence of Fenton's reagent as chemical oxidant were studied. The influence of these factors on the biochemical constituents and population of total bacteria were also investigated. Aluminium anode was found to be more effective to remove pollutants and maximum removal of BOD took place within 30 min of electrolysis. After electrochemical treatment phosphate removal efficiency was 99.5% and complete removal of sulphide was observed from the anaerobically treated effluent. Electrochemical treatment is effective in removing biochemical constituents and total bacteria in the presence of Fenton's reagent.

  8. Short communication: The water footprint of dairy products: case study involving skim milk powder.

    PubMed

    Ridoutt, B G; Williams, S R O; Baud, S; Fraval, S; Marks, N

    2010-11-01

    In the context of global water scarcity and food security concerns, water footprints are emerging as an important sustainability indicator in the agriculture and food sectors. Using a recently developed life cycle assessment-based methodology that takes into account local water stress where operations occur, the normalized water footprints of milk products from South Gippsland, one of Australia's major dairy regions, were 14.4 L/kg of total milk solids in whole milk (at farm gate) and 15.8 L/kg of total milk solids in skim milk powder (delivered to export destination). These results demonstrate that dairy products can be produced with minimal potential to contribute to freshwater scarcity. However, not all dairy production systems are alike and the variability in water footprints between systems and products should be explored to obtain strategic insights that will enable the dairy sector to minimize its burden on freshwater systems from consumptive water use. Copyright © 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  9. Production of bacteriocin-like inhibitory substance by Bifidobacterium lactis in skim milk supplemented with additives.

    PubMed

    Martinez, Fabio Andres Castillo; Domínguez, José Manuel; Converti, Attilio; Oliveira, Ricardo Pinheiro de Souza

    2015-08-01

    Bacteriocins are natural compounds used as food biopreservatives instead of chemical preservatives. Bifidobacterium animalis subsp. lactis (Bifid. lactis) was shown to produce a bacteriocin-like inhibitory substance (BLIS) able to inhibit the growth of Listeria monocytogenes selected as an indicator microorganism. To enhance this production by the strain Bifid. lactis BL 04, skim milk (SM) was used as a fermentation medium either in the presence or in the absence of yeast extract, Tween 80 or inulin as stimulating additives, and the results in terms of bacterial growth and BLIS production were compared with those obtained in a traditional high cost complex medium such as Man, Rogosa and Sharpe (MRS). To this purpose, all the cultivations were carried out in flasks at 200 rpm under anaerobic conditions ensured by a nitrogen flowrate of 1.0 L/min for 48 h, and BLIS production was quantified by means of a modified agar diffusion assay at low values of both temperature and concentration of List. monocytogenes. Although all these ingredients were shown to exert positive influence on BLIS production in both media, yeast extract and SM were by far the best ingredient and the best medium, respectively, allowing for a BLIS production at the late exponential phase of 2000 AU/ml.

  10. Transformation from proper time on earth to coordinate time in solar system barycentric space-time frame of reference

    NASA Technical Reports Server (NTRS)

    Moyer, T. D.

    1976-01-01

    An expression was derived for the time transformation t - tau, where t is coordinate time in the solar system barycentric space-time frame of reference and tau is proper time obtained from a fixed atomic clock on earth. This transformation is suitable for use in the computation of high-precision earth-based range and Doppler observables of a spacecraft or celestial body located anywhere in the solar system; it can also be used in obtaining computed values of very long baseline interferometry data types. The formulation for computing range and Doppler observables, which is an explicit function of the transformation t - tau, is described briefly.

  11. Studies of tau- to h- h- h+ nu and tau- to K- pi0 nu Decays at BaBar

    SciTech Connect

    Nugent, I.M.; /Victoria U.

    2007-10-24

    We present preliminary inclusive branching fraction measurements of {tau}{sup -} {yields} h{sup -}h{sup -}h{sup +}{nu} (h = {pi} or K) and {tau}{sup -} K{sup -}{pi}{sup 0}{nu} decay modes using a sample of {tau}-pair events collected by the BABAR detector at the SLAC PEP-II asymmetric e{sup +}e{sup -} storage ring. The branching fractions of {tau}{sup -} {yields} {pi}{sup -}{pi}{sup -}{pi}{sup +}, {tau}{sup -} {yields} K{sup -}{pi}{sup -}{pi}{sup +}{nu}, and {tau}{sup -} {yields} K{sup -}{pi}{sup -}K{sup +}{nu} are measured with higher precision than previously published results and the inclusive branching fraction {tau}{sup -} {yields} K{sup -}K{sup -}K{sup +}{nu} is measured for the first time. In addition, the first measurement of the branching fraction {tau}{sup -} {yields} {pi}{sup -}{phi}{nu} and the measurement of the branching fraction {tau}{sup -} {yields} K{sup -}{phi}{nu} are determined by means of a binned maximum likelihood fit to the K{sup +}K{sup -} invariant mass distribution. These branching fractions are extracted by means of a migration matrix that accounts for the cross contamination between the {tau}{sup -} {yields} h{sup -}h{sup -}h{sup +}{nu} modes. The preliminary {tau}{sup -} {yields} K{sup -}{pi}{sup 0}{nu} branching fraction and invariant mass distributions are also presented in this paper.

  12. Tau-Induced Ca(2+)/Calmodulin-Dependent Protein Kinase-IV Activation Aggravates Nuclear Tau Hyperphosphorylation.

    PubMed

    Wei, Yu-Ping; Ye, Jin-Wang; Wang, Xiong; Zhu, Li-Ping; Hu, Qing-Hua; Wang, Qun; Ke, Dan; Tian, Qing; Wang, Jian-Zhi

    2017-06-23

    Hyperphosphorylated tau is the major protein component of neurofibrillary tangles in the brains of patients with Alzheimer's disease (AD). However, the mechanism underlying tau hyperphosphorylation is not fully understood. Here, we demonstrated that exogenously expressed wild-type human tau40 was detectable in the phosphorylated form at multiple AD-associated sites in cytoplasmic and nuclear fractions from HEK293 cells. Among these sites, tau phosphorylated at Thr205 and Ser214 was almost exclusively found in the nuclear fraction at the conditions used in the present study. With the intracellular tau accumulation, the Ca(2+) concentration was significantly increased in both cytoplasmic and nuclear fractions. Further studies using site-specific mutagenesis and pharmacological treatment demonstrated that phosphorylation of tau at Thr205 increased nuclear Ca(2+) concentration with a simultaneous increase in the phosphorylation of Ca(2+)/calmodulin-dependent protein kinase IV (CaMKIV) at Ser196. On the other hand, phosphorylation of tau at Ser214 did not significantly change the nuclear Ca(2+)/CaMKIV signaling. Finally, expressing calmodulin-binding protein-4 that disrupts formation of the Ca(2+)/calmodulin complex abolished the okadaic acid-induced tau hyperphosphorylation in the nuclear fraction. We conclude that the intracellular accumulation of phosphorylated tau, as detected in the brains of AD patients, can trigger nuclear Ca(2+)/CaMKIV signaling, which in turn aggravates tau hyperphosphorylation. Our findings provide new insights for tauopathies: hyperphosphorylation of intracellular tau and an increased Ca(2+) concentration may induce a self-perpetuating harmful loop to promote neurodegeneration.

  13. Tau and neurodegenerative disease: the story so far.

    PubMed

    Iqbal, Khalid; Liu, Fei; Gong, Cheng-Xin

    2016-01-01

    In 1975, tau protein was isolated as a microtubule-associated factor from the porcine brain. In the previous year, a paired helical filament (PHF) protein had been identified in neurofibrillary tangles in the brains of individuals with Alzheimer disease (AD), but it was not until 1986 that the PHF protein and tau were discovered to be one and the same. In the AD brain, tau was found to be abnormally hyperphosphorylated, and it inhibited rather than promoted in vitro microtubule assembly. Almost 80 disease-causing exonic missense and intronic silent mutations in the tau gene have been found in familial cases of frontotemporal dementia but, to date, no such mutation has been found in AD. The first phase I clinical trial of an active tau immunization vaccine in patients with AD was recently completed. Assays for tau levels in cerebrospinal fluid and plasma are now available, and tau radiotracers for PET are under development. In this article, we provide an overview of the pivotal discoveries in the tau research field over the past 40 years. We also review the current status of the field, including disease mechanisms and therapeutic approaches.

  14. Widespread tau seeding activity at early Braak stages.

    PubMed

    Furman, Jennifer L; Vaquer-Alicea, Jaime; White, Charles L; Cairns, Nigel J; Nelson, Peter T; Diamond, Marc I

    2017-01-01

    Transcellular propagation of tau aggregates may underlie the progression of pathology in Alzheimer's disease (AD) and other tauopathies. Braak staging (B1, B2, B3) is based on phospho-tau accumulation within connected brain regions: entorhinal cortex (B1); hippocampus/limbic system (B2); and frontal and parietal lobes (B3). We previously developed a specific and sensitive assay that uses flow cytometry to quantify tissue seeding activity based on fluorescence resonance energy transfer (FRET) in cells that stably express tau reporter proteins. In a tauopathy mouse model, we have detected seeding activity far in advance of histopathological changes. It remains unknown whether individuals with AD also develop seeding activity prior to accumulation of phospho-tau. We measured tau seeding activity across four brain regions (hippocampus, frontal lobe, parietal lobe, and cerebellum) in 104 fresh-frozen human AD brain samples from all Braak stages. We observed widespread seeding activity, notably in regions predicted to be free of phospho-tau deposition, and in detergent-insoluble fractions that lacked tau detectable by ELISA. Seeding activity correlated positively with Braak stage and negatively with MMSE. Our results are consistent with early transcellular propagation of tau seeds that triggers subsequent development of neuropathology. The FRET-based seeding assay may also complement standard neuropathological classification of tauopathies.

  15. Dimethyl sulfoxide induces both direct and indirect tau hyperphosphorylation.

    PubMed

    Julien, Carl; Marcouiller, François; Bretteville, Alexis; El Khoury, Noura B; Baillargeon, Joanie; Hébert, Sébastien S; Planel, Emmanuel

    2012-01-01

    Dimethyl sulfoxide (DMSO) is widely used as a solvent or vehicle for biological studies, and for treatment of specific disorders, including traumatic brain injury and several forms of amyloidosis. As Alzheimer's disease (AD) brains are characterized by deposits of β-amyloid peptides, it has been suggested that DMSO could be used as a treatment for this devastating disease. AD brains are also characterized by aggregates of hyperphosphorylated tau protein, but the effect of DMSO on tau phosphorylation is unknown. We thus investigated the impact of DMSO on tau phosphorylation in vitro and in vivo. One hour following intraperitoneal administration of 1 or 2 ml/kg DMSO in mice, no change was observed in tau phosphorylation. However, at 4 ml/kg, tau was hyperphosphorylated at AT8 (Ser(202)/Thr(205)), PHF-1 (Ser(396)/Ser(404)) and AT180 (Thr(231)) epitopes. At this dose, we also noticed that the animals were hypothermic. When the mice were maintained normothermic, the effect of 4 ml/kg DMSO on tau hyperphosphorylation was prevented. On the other hand, in SH-SY5Y cells, 0.1% DMSO induced tau hyperphosphorylation at AT8 and AT180 phosphoepitopes in normothermic conditions. Globally, these findings demonstrate that DMSO can induce tau hyperphosphorylation indirectly via hypothermia in vivo, and directly in vitro. These data should caution researchers working with DMSO as it can induce artifactual results both in vivo and in vitro.

  16. Caspase-2 cleavage of tau reversibly impairs memory.

    PubMed

    Zhao, Xiaohui; Kotilinek, Linda A; Smith, Benjamin; Hlynialuk, Chris; Zahs, Kathleen; Ramsden, Martin; Cleary, James; Ashe, Karen H

    2016-11-01

    In Alzheimer's disease (AD) and other tauopathies, the tau protein forms fibrils, which are believed to be neurotoxic. However, fibrillar tau has been dissociated from neuron death and network dysfunction, suggesting the involvement of nonfibrillar species. Here we describe a novel pathological process in which caspase-2 cleavage of tau at Asp314 impairs cognitive and synaptic function in animal and cellular models of tauopathies by promoting the missorting of tau to dendritic spines. The truncation product, Δtau314, resists fibrillation and is present at higher levels in brains from cognitively impaired mice and humans with AD. The expression of tau mutants that resisted caspase-2 cleavage prevented tau from infiltrating spines, dislocating glutamate receptors and impairing synaptic function in cultured neurons, and it prevented memory deficits and neurodegeneration in mice. Decreasing the levels of caspase-2 restored long-term memory in mice that had existing deficits. Our results suggest an overall treatment strategy for re-establishing synaptic function and restoring memory in patients with AD by preventing tau from accumulating in dendritic spines.

  17. Morin attenuates tau hyperphosphorylation by inhibiting GSK3β

    PubMed Central

    Gong, Eun Ji; Park, Hee Ra; Kim, Mi Eun; Piao, Shunfu; Lee, Eunjin; Jo, Dong-Gyu; Chung, Hae Young; Ha, Nam-Chul; Mattson, Mark P.; Lee, Jaewon

    2011-01-01

    Alzheimer’s disease (AD) is the major form of age-related dementia and is characterized by progressive cognitive impairment, the accumulation of extracellular amyloid β-peptide (Aβ), and intracellular hyperphosphorylated tau aggregates in affected brain regions. Tau hyperphosphorylation and accumulation in neurofibrillary tangles is strongly correlated with cognitive deficits, and is apparently a critical event in the dementia process because mutations in tau can cause a tangle-only form of dementia called frontotemporal lobe dementia. Among kinases that phosphorylate tau, glycogen synthase kinase 3β (GSK3β) is strongly implicated in AD pathogenesis. In the present study, we established an ELISA to screen for agents that inhibit GSK3β activity and found that the flavonoid morin effectively inhibited GSK3β activity and blocked GSK3β-induced tau phosphorylation in vitro. In addition, morin attenuated Aβ-induced tau phosphorylation and protected human neuroblastoma cells against Aβ cytotoxicity. Furthermore, treatment of 3×Tg-AD mice with morin resulted in reductions in tau hyperphosphorylation and paired helical filament-like immunoreactivity in hippocampal neurons. Morin is a novel inhibitor of GSK3β that can reduce tau pathology in vivo and may have potential as a therapeutic agent in tauopathies. PMID:21782947

  18. Dimethyl Sulfoxide Induces Both Direct and Indirect Tau Hyperphosphorylation

    PubMed Central

    Julien, Carl; Marcouiller, François; Bretteville, Alexis; El Khoury, Noura B.; Baillargeon, Joanie; Hébert, Sébastien S.; Planel, Emmanuel

    2012-01-01

    Dimethyl sulfoxide (DMSO) is widely used as a solvent or vehicle for biological studies, and for treatment of specific disorders, including traumatic brain injury and several forms of amyloidosis. As Alzheimer’s disease (AD) brains are characterized by deposits of β-amyloid peptides, it has been suggested that DMSO could be used as a treatment for this devastating disease. AD brains are also characterized by aggregates of hyperphosphorylated tau protein, but the effect of DMSO on tau phosphorylation is unknown. We thus investigated the impact of DMSO on tau phosphorylation in vitro and in vivo. One hour following intraperitoneal administration of 1 or 2 ml/kg DMSO in mice, no change was observed in tau phosphorylation. However, at 4 ml/kg, tau was hyperphosphorylated at AT8 (Ser202/Thr205), PHF-1 (Ser396/Ser404) and AT180 (Thr231) epitopes. At this dose, we also noticed that the animals were hypothermic. When the mice were maintained normothermic, the effect of 4 ml/kg DMSO on tau hyperphosphorylation was prevented. On the other hand, in SH-SY5Y cells, 0.1% DMSO induced tau hyperphosphorylation at AT8 and AT180 phosphoepitopes in normothermic conditions. Globally, these findings demonstrate that DMSO can induce tau hyperphosphorylation indirectly via hypothermia in vivo, and directly in vitro. These data should caution researchers working with DMSO as it can induce artifactual results both in vivo and in vitro. PMID:22768202

  19. Methylglyoxal induces tau hyperphosphorylation via promoting AGEs formation.

    PubMed

    Li, Xiao-Hong; Xie, Jia-Zhao; Jiang, Xia; Lv, Bing-Ling; Cheng, Xiang-Shu; Du, Lai-Ling; Zhang, Jia-Yu; Wang, Jian-Zhi; Zhou, Xin-Wen

    2012-12-01

    The hyperphosphorylated tau is a major protein component of neurofibrillary tangle, which is one of hallmarks of Alzheimer's disease (AD). While the level of methylglyoxal (MG) is significantly increased in the AD brains, the role of MG in tau phosphorylation is still not reported. Here, we found that MG could induce tau hyperphosphorylation at multiple AD-related sites in neuroblastoma 2a cells under maintaining normal cell viability. MG treatment increased the level of advanced glycation end products (AGEs) and the receptor of AGEs (RAGE). Glycogen synthesis kinase-3β (GSK-3β) and p38 MAPK were activated, whereas the level and activity of JNK, Erk1/2, cdk5, and PP2A were not altered after MG treatment. Simultaneous inhibition of GSK-3β or p38 attenuated the MG-induced tau hyperphosphorylation. Aminoguanidine, a blocker of AGEs formation, could effectively reverse the MG-induced tau hyperphosphorylation. These data suggest that MG induces AD-like tau hyperphosphorylation through AGEs formation involving RAGE up-regulation and GSK-3β activation and p38 activation is also partially involved in MG-induced tau hyperphosphorylation. Thus, targeting MG may be a promising therapeutic strategy to prevent AD-like tau hyperphosphorylation.

  20. Importance of precision measurements in the tau sector

    SciTech Connect

    Pich, A.

    1996-01-01

    {tau} decays provide a powerful tool to test the structure of the weak currents and the universality of their couplings to the {ital W} boson. The constraints implied by present data and the possible improvements at the {tau}cF are analyzed. {copyright} {ital 1996 American Institute of Physics.}

  1. Structural evaluations of tau protein conformation: methodologies and approaches.

    PubMed

    Zabik, Nicole L; Imhof, Matthew M; Martic-Milne, Sanela

    2017-06-01

    Protein-misfolding diseases are based on a common principle of aggregation initiated by intra- and inter-molecular contacts. The structural and conformational changes induced by biochemical transformations such as post-translational modifications (PTMs), often lead to protein unfolding and misfolding. Thus, these order-to-disorder or disorder-to-order transitions may regulate cellular function. Tau, a neuronal protein, regulates microtubule (MT) structure and overall cellular integrity. However, misfolded tau modified by PTMs results in MT destabilization, toxic tau aggregate formation, and ultimately cell death, leading to neurodegeneration. Currently, the lack of structural information surrounding tau severely limits understanding of neurodegeneration. This minireview focuses on the current methodologies and approaches aimed at probing tau conformation and the role of conformation in various aspects of tau biochemistry. The recent applications of nuclear magnetic resonance, mass spectrometry, Förster resonance electron transfer, and molecular dynamics simulations toward structural analysis of conformational landscapes of tau will be described. The strategies developed for structural evaluation of tau may significantly improve our understanding of misfolding diseases.

  2. Identification of nuclear. tau. isoforms in human neuroblastoma cells

    SciTech Connect

    Loomis, P.A.; Howard, T.H.; Castleberry, R.P.; Binder, L.I. )

    1990-11-01

    The {tau} proteins have been reported only in association with microtubules and with ribosomes in situ, in the normal central nervous system. In addition, {tau} has been shown to be an integral component of paired helical filaments, the principal constituent of the neurofibrillary tangles found in brains of patients with Alzheimer's disease and of most aged individuals with Down syndrome (trisomy 21). The authors report here the localization of the well-characterized Tau-1 monoclonal antibody to the nucleolar organizer regions of the acrocentric chromosomes and to their interphase counterpart, the fibrillar component of the nucleolus, in human neuroblastoma cells. Similar localization to the nucleolar organizer regions was also observed in other human cell lines and in one monkey kidney cell line but was not seen in non-primate species. Immunochemically, they further demonstrated the existence of the entire {tau} molecule in the isolated nuclei of neuroblastoma cells. Nuclear {tau} proteins, like the {tau} proteins of the paired helical filaments, cannot be extracted in standard SDS-containing electrophoresis sample buffer but require pretreatment with formic acid prior to immunoblot analysis. This work indicates that {tau} may function in processes not directly associated with microtubules and that highly insoluble complexes of {tau} may also play a role in normal cellular physiology.

  3. Effect of beta-lactoglobulin A and B whey protein variants on the rennet-induced gelation of skim milk gels in a model reconstituted skim milk system.

    PubMed

    Meza-Nieto, M A; Vallejo-Cordoba, B; González-Córdova, A F; Félix, L; Goycoolea, F M

    2007-02-01

    The effect of fortifying reconstituted skim milk with increasing levels of the beta-lactoglobulin (beta-LG) genetic variants A, B, and an A-B mixture on rennet-induced gelation was studied by small deformation-sensitive rheology. Free-zone capillary electrophoresis and high-sensitivity oscillatory rheology were used to elucidate the role of potential heterotypic associative interactions between whey proteins and casein in a mixed colloidal system, subjected to moderate heating (65 degrees C for 30 min) prior to renneting, on the gelling properties of the system. Increasing levels of added whey protein, in the concentration range of 0.225 to 1.35% of added protein, led to a concomitant progressive increase in the equilibrium shear storage modulus, G' (recorded after approximately 10,800 s), in the order beta-LG B > beta-LG A and beta-LG A-B, as the general expected consequence of the setup of denser casein gel networks. The preferential effect of beta-LG B over beta-LG A on the mechanical strength of the gels may be due to the formation of cross-links and aggregates involving whey proteins and rennet hydrolysis products or an increase in the size of the casein micelle caused by the grafting of beta-LG B to its surface, or both. The results of free-zone capillary electrophoresis were consistent with the notion that beta-LG B (and not beta-LG A) binds to the casein micelle under an optimal stoichiometry of 1:0.045 (mg/mg), even in the absence of heat treatment. The liquid-like character of the gel networks formed, tan delta, was a parameter sensitive to the level of addition of beta-LG A in particular. At low concentrations (up to 0.45%) of beta-LG A, tan delta increased by almost twice as much, which was interpreted as a result of the increase in the loss modulus, G'', of the sol fraction because of the presence of unbound beta-LG A. At greater incremental concentrations of beta-LG (>0.45%), the formation of smaller whey protein aggregates confined to the sol

  4. The influence of ultra-pasteurization by indirect heating versus direct steam injection on skim and 2% fat milks.

    PubMed

    Lee, A P; Barbano, D M; Drake, M A

    2017-03-01

    Fluid milk is traditionally pasteurized by high temperature, short time (HTST) pasteurization, which requires heating to at least 72°C for 15 s. Ultra-pasteurization (UP) extends milk shelf life and is defined as heating to at least 138°C for 2 s. The UP process can be done by indirect heating (IND) or by direct steam injection (DSI). The influence of these 2 UP methods on milk flavor has not been widely investigated. The objective of this study was to compare the effect of HTST, IND-UP, and DSI-UP on sensory perception of fluid milk. Raw skim and standardized 2% milks were pasteurized at 140°C for 2.3 s by IND or DSI or by HTST (78°C, 15 s) and homogenized at 20.7 MPa. The processed milks were stored in light-shielded opaque high-density polyethylene containers at 4°C and examined by descriptive analysis and microbial analysis on d 3, 7, and 14. Furosine and serum protein denaturation analyses were performed on d 0 and 14 as an indicator of heat treatment. Last, consumer acceptance testing was conducted at d 10, with adults (n = 250) and children (ages 8 to13 y, n = 100) who were self-reported consumers of skim or 2% milk; consumers only received samples for either skim or 2% milk. The entire experiment was repeated in triplicate. Milks treated by HTST had lower cooked flavor than either UP milk. Milks heated by DSI-UP were characterized by sulfur or eggy and cooked flavors, whereas IND-UP milks had higher sweet aromatic and sweet taste compared with DSI-UP milk. Aromatic flavor intensities of all milks decreased across 14 d of storage. Furosine concentrations and serum protein denaturation were highest for the IND treatments, followed by DSI and HTST. Furosine content in both skim and 2% milk increased with time, but the increase was faster in IND-UP skim milk. Adult and child consumers preferred HTST milk over either UP milk, regardless of fat content. Ultra-pasteurization by IND or DSI did not affect consumer acceptance at 10 d postprocessing, but

  5. An autoradiographic evaluation of AV-1451 Tau PET in dementia.

    PubMed

    Lowe, Val J; Curran, Geoffry; Fang, Ping; Liesinger, Amanda M; Josephs, Keith A; Parisi, Joseph E; Kantarci, Kejal; Boeve, Bradley F; Pandey, Mukesh K; Bruinsma, Tyler; Knopman, David S; Jones, David T; Petrucelli, Leonard; Cook, Casey N; Graff-Radford, Neill R; Dickson, Dennis W; Petersen, Ronald C; Jack, Clifford R; Murray, Melissa E

    2016-06-13

    It is essential to determine the specificity of AV-1451 PET for tau in brain imaging by using pathological comparisons. We performed autoradiography in autopsy-confirmed Alzheimer disease and other neurodegenerative disorders to evaluate the specificity of AV-1451 binding for tau aggregates. Tissue samples were selected that had a variety of dementia-related neuropathologies including Alzheimer disease, primary age-related tauopathy, tangle predominant dementia, non-Alzheimer disease tauopathies, frontotemporal dementia, parkinsonism, Lewy body disease and multiple system atrophy (n = 38). Brain tissue sections were stained for tau, TAR DNA-binding protein-43, and α-synuclein and compared to AV-1451 autoradiography on adjacent sections. AV-1451 preferentially localized to neurofibrillary tangles, with less binding to areas enriched in neuritic pathology and less mature tau. The strength of AV-1451 binding with respect to tau isoforms in various neurodegenerative disorders was: 3R + 4R tau (e.g., AD) > 3R tau (e.g., Pick disease) or 4R tau. Only minimal binding of AV-1451 to TAR DNA-binding protein-43 positive regions was detected. No binding of AV-1451 to α-synuclein was detected. "Off-target" binding was seen in vessels, iron-associated regions, substantia nigra, calcifications in the choroid plexus, and leptomeningeal melanin. Reduced AV-1451 binding in neuritic pathology compared to neurofibrillary tangles suggests that the maturity of tau pathology may affect AV-1451 binding and suggests complexity in AV-1451 binding. Poor association of AV-1451 with tauopathies that have preferential accumulation of either 4R tau or 3R tau suggests limited clinical utility in detecting these pathologies. In contrast, for disorders associated with 3R + 4R tau, such as Alzheimer disease, AV-1451 binds tau avidly but does not completely reflect the early stage tau progression suggested by Braak neurofibrillary tangle staging. AV-1451 binding to TAR DNA

  6. Period Change and Evolutionary Status of SW Tau

    NASA Astrophysics Data System (ADS)

    Devlen, Ahmet; Acar, Mert

    2017-03-01

    In this work, the relation between the period change and evolutionary status of SW Tau, a Type II Cepheid variable, is examined. An (O-C) analysis of the times of maxima of SW Tau has been undertaken to determine this relation. SW Tau has the characteristic light curve shape of BL Her type stars. By taking into consideration SW Tau’s well-defined period decrease, obtained from the photometric observations, its position on the HR diagram in accordance with evolutionary models, and its chemical composition, we demonstrate that SW Tau is a Cepheid crossing the instability strip for the fourth time. SW Tau could be interpreted as being an early AGB star on the blueward evolutionary phase during shell helium burning.

  7. Searching for anomalous {tau}{nu}W couplings

    SciTech Connect

    Rizzo, T.G.

    1997-09-01

    The capability of current and future measurements at low and high energy e{sup +}e{sup {minus}} colliders to probe for the existence of anomalous, CP-conserving, {tau}{nu}W dipole moment-type couplings is examined. At present, constraints on the universality of the {tau} charged and neutral current interactions as well as the shape of the {tau}{r_arrow}scr(l) energy spectrum provide the strongest bounds on such anomalous couplings. The presence of these dipole moments are shown to influence, e.g., the extraction of {alpha}{sub s}(m{sub {tau}}{sup 2}) from {tau} decays and can lead to apparent violations of CVC expectations. {copyright} {ital 1997} {ital The American Physical Society}

  8. Tau co-organizes dynamic microtubule and actin networks

    PubMed Central

    Elie, Auréliane; Prezel, Elea; Guérin, Christophe; Denarier, Eric; Ramirez-Rios, Sacnicte; Serre, Laurence; Andrieux, Annie; Fourest-Lieuvin, Anne; Blanchoin, Laurent; Arnal, Isabelle

    2015-01-01

    The crosstalk between microtubules and actin is essential for cellular functions. However, mechanisms underlying the microtubule-actin organization by cross-linkers remain largely unexplored. Here, we report that tau, a neuronal microtubule-associated protein, binds to microtubules and actin simultaneously, promoting in vitro co-organization and coupled growth of both networks. By developing an original assay to visualize concomitant microtubule and actin assembly, we show that tau can induce guided polymerization of actin filaments along microtubule tracks and growth of single microtubules along actin filament bundles. Importantly, tau mediates microtubule-actin co-alignment without changing polymer growth properties. Mutagenesis studies further reveal that at least two of the four tau repeated motifs, primarily identified as tubulin-binding sites, are required to connect microtubules and actin. Tau thus represents a molecular linker between microtubule and actin networks, enabling a coordination of the two cytoskeletons that might be essential in various neuronal contexts. PMID:25944224

  9. Anticipating arrival: is the tau margin a specious theory?

    PubMed

    Wann, J P

    1996-08-01

    A critical review is presented of previous studies that have examined the use of the tau margin (tau m) in the temporal judgment of arrival in natural contexts. This body of evidence is frequently cited as providing strong support for the use of Tau m for interceptive timing. Critical flaws are demonstrated in either the analysis or interpretation of many of these studies. It is suggested that temporal control in a number of these experiments could have been effected using a relative distance estimate (zeta ratio). Results are also presented and discussed that conflict with the tau m control hypothesis. It is concluded that although the tau m hypothesis provides an appealing account of interceptive timing, its broad acceptance is unwarranted on the evidence available.

  10. MAGIC gamma-ray telescopes hunting for tau neutrinos

    NASA Astrophysics Data System (ADS)

    Góra, D.; Bernardini, E.; Manganaro, M.; López, M.

    2017-01-01

    The MAGIC telescopes, located at the Roque de los Muchachos Observatory (2200 a.s.l.) in the Canary Island of La Palma, can perform observations pointing directly the sea. This permits to search for signatures of air showers induced by tau neutrinos in the PeV-EeV energy range arising from the ocean. We have studied the MAGIC response to such events, employing Monte Carlo simulations of upward-going tau neutrino showers. The analysis of the simulated shower images shows that air showers induced by tau neutrinos can be discriminated from the background of very inclined hadronic showers. We have calculated the point source acceptance and the expected event rates, assuming an incoming tau neutrino flux consistent with IceCube measurements and for a sample of generic neutrino fluxes from photo-hadronic interactions in AGNs. Finally, we report our first results from the tau neutrino search with the MAGIC telescopes.

  11. Mechanisms of tau and Aβ-induced excitotoxicity.

    PubMed

    Pallo, Susanne P; DiMaio, John; Cook, Alexis; Nilsson, Bradley; Johnson, Gail V W

    2016-03-01

    Excitotoxicity was originally postulated to be a late stage side effect of Alzheimer׳s disease (AD)-related neurodegeneration, however more recent studies indicate that it may occur early in AD and contribute to the neurodegenerative process. Tau and amyloid beta (Aβ), the main components of neurofibrillary tangles (NFTs) and amyloid plaques, have been implicated in cooperatively and independently facilitating excitotoxicity. Our study investigated the roles of tau and Aβ in AD-related excitotoxicity. In vivo studies showed that tau knockout (tau(-/-)) mice were significantly protected from seizures and hippocampal superoxide production induced with the glutamate analog, kainic acid (KA). We hypothesized that tau accomplished this by facilitating KA-induced Ca(2+) influx into neurons, however lentiviral tau knockdown failed to ameliorate KA-induced Ca(2+) influx into primary rat cortical neurons. We further investigated if tau cooperated with Aβ to facilitate KA-induced Ca(2+) influx. While Aβ biphasically modulated the KA-induced Cacyt(2+) responses, tau knockdown continued to have no effect. Therefore, tau facilitates KA-induced seizures and superoxide production in a manner that does not involve facilitation of Ca(2+) influx through KA receptors (KAR). On the other hand, acute pretreatment with Aβ (10 min) enhanced KA-induced Ca(2+) influx, while chronic Aβ (24 h) significantly reduced it, regardless of tau knockdown. Given previously published connections between Aβ, group 1 metabotropic glutamate receptors (mGluRs), and KAR regulation, we hypothesized that Aβ modulates KAR via a G-protein coupled receptor pathway mediated by group 1 mGluRs. We found that Aβ did not activate group 1 mGluRs and inhibition of these receptors did not reverse Aβ modulation of KA-induced Ca(2+) influx. Therefore, Aβ biphasically regulates KAR via a mechanism that does not involve group 1mGluR activation.

  12. 14-3-3ζ Mediates Tau Aggregation in Human Neuroblastoma M17 Cells.

    PubMed

    Li, Tong; Paudel, Hemant K

    2016-01-01

    Microtubule-associated protein tau is the major component of paired helical filaments (PHFs) associated with the neuropathology of Alzheimer's disease (AD). Tau in the normal brain binds and stabilizes microtubules. Tau isolated from PHFs is hyperphosphorylated, which prevents it from binding to microtubules. Tau phosphorylation has been suggested to be involved in the development of NFT pathology in the AD brain. Recently, we showed that 14-3-3ζ is bound to tau in the PHFs and when incubated in vitro with 14-3-3ζ, tau formed amorphous aggregates, single-stranded straight filaments, double stranded ribbon-like filaments and PHF-like filaments that displayed close resemblance with corresponding ultrastructures of AD brain. Surprisingly however, phosphorylated and non-phosphorylated tau aggregated in a similar manner, indicating that tau phosphorylation does not affect in vitro tau aggregation (Qureshi et al (2013) Biochemistry 52, 6445-6455). In this study, we have examined the role of tau phosphorylation in tau aggregation in cellular level. We have found that in human M17 neuroblastoma cells, tau phosphorylation by GSK3β or PKA does not cause tau aggregation, but promotes 14-3-3ζ-induced tau aggregation by destabilizing microtubules. Microtubule disrupting drugs also promoted 14-3-3ζ-induced tau aggregation without changing tau phosphorylation in M17 cell. In vitro, when incubated with 14-3-3ζ and microtubules, nonphosphorylated tau bound to microtubules and did not aggregate. Phosphorylated tau on the other hand did not bind to microtubules and aggregated. Our data indicate that microtubule-bound tau is resistant to 14-3-3ζ-induced tau aggregation and suggest that tau phosphorylation promotes tau aggregation in the brain by detaching tau from microtubules and thus making it accessible to 14-3-3ζ.

  13. 14-3-3ζ Mediates Tau Aggregation in Human Neuroblastoma M17 Cells

    PubMed Central

    Li, Tong; Paudel, Hemant K.

    2016-01-01

    Microtubule-associated protein tau is the major component of paired helical filaments (PHFs) associated with the neuropathology of Alzheimer’s disease (AD). Tau in the normal brain binds and stabilizes microtubules. Tau isolated from PHFs is hyperphosphorylated, which prevents it from binding to microtubules. Tau phosphorylation has been suggested to be involved in the development of NFT pathology in the AD brain. Recently, we showed that 14-3-3ζ is bound to tau in the PHFs and when incubated in vitro with 14-3-3ζ, tau formed amorphous aggregates, single-stranded straight filaments, double stranded ribbon-like filaments and PHF-like filaments that displayed close resemblance with corresponding ultrastructures of AD brain. Surprisingly however, phosphorylated and non-phosphorylated tau aggregated in a similar manner, indicating that tau phosphorylation does not affect in vitro tau aggregation (Qureshi et al (2013) Biochemistry 52, 6445–6455). In this study, we have examined the role of tau phosphorylation in tau aggregation in cellular level. We have found that in human M17 neuroblastoma cells, tau phosphorylation by GSK3β or PKA does not cause tau aggregation, but promotes 14-3-3ζ-induced tau aggregation by destabilizing microtubules. Microtubule disrupting drugs also promoted 14-3-3ζ-induced tau aggregation without changing tau phosphorylation in M17 cell. In vitro, when incubated with 14-3-3ζ and microtubules, nonphosphorylated tau bound to microtubules and did not aggregate. Phosphorylated tau on the other hand did not bind to microtubules and aggregated. Our data indicate that microtubule-bound tau is resistant to 14-3-3ζ-induced tau aggregation and suggest that tau phosphorylation promotes tau aggregation in the brain by detaching tau from microtubules and thus making it accessible to 14-3-3ζ. PMID:27548710

  14. Measurement of the Semileptonic B-bar->D{sup (*)}{tau}{nu}-bar{sub {tau}} Decays at BABAR

    SciTech Connect

    Lopes Pegna, David

    2010-02-10

    Semileptonic B meson decays into final states containing the tau lepton are of interesting as they provide information on the Standard Model as well as a window on new physics effects. We present results on B-bar->D{sup (*)}taunu-bar{sub tau} decays where the second B in the event is fully reconstructed.

  15. O-GlcNAc modification of tau directly inhibits its aggregation without perturbing the conformational properties of tau monomers.

    PubMed

    Yuzwa, Scott A; Cheung, Adrienne H; Okon, Mark; McIntosh, Lawrence P; Vocadlo, David J

    2014-04-17

    The aggregation of the microtubule-associated protein tau into paired helical filaments to form neurofibrillary tangles constitutes one of the pathological hallmarks of Alzheimer's disease. Tau is post-translationally modified by the addition of N-acetyl-D-glucosamine O-linked to several serine and threonine residues (O-GlcNAc). Previously, increased O-GlcNAcylation of tau has been shown to block the accumulation of tau aggregates within a tauopathy mouse model. Here we show that O-GlcNAc modification of full-length human tau impairs the rate and extent of its heparin-induced aggregation without perturbing its activity toward microtubule polymerization. O-GlcNAcylation, however, does not impact the "global-fold" of tau as measured by a Förster resonance energy transfer assay. Similarly, nuclear magnetic resonance studies demonstrated that O-GlcNAcylation only minimally perturbs the local structural and dynamic features of a tau fragment (residues 353-408) spanning the last microtubule binding repeat to the major GlcNAc-acceptor Ser400. These data indicate that the inhibitory effects of O-GlcNAc on tau aggregation may result from enhanced monomer solubility or the destabilization of fibrils or soluble aggregates, rather than by altering the conformational properties of the monomeric protein. This work further underscores the potential of targeting the O-GlcNAc pathway for potential Alzheimer's disease therapeutics. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Tau-Targeted Immunization Impedes Progression of Neurofibrillary Histopathology in Aged P301L Tau Transgenic Mice

    PubMed Central

    Bi, Mian; Ittner, Arne; Ke, Yazi D.; Götz, Jürgen; Ittner, Lars M.

    2011-01-01

    In Alzheimer's disease (AD) brains, the microtubule-associated protein tau and amyloid-β (Aβ) deposit as intracellular neurofibrillary tangles (NFTs) and extracellular plaques, respectively. Tau deposits are furthermore found in a significant number of frontotemporal dementia cases. These diseases are characterized by progressive neurodegeneration, the loss of intellectual capabilities and behavioral changes. Unfortunately, the currently available therapies are limited to symptomatic relief. While active immunization against Aβ has shown efficacy in both various AD mouse models and patients with AD, immunization against pathogenic tau has only recently been shown to prevent pathology in young tau transgenic mice. However, if translated to humans, diagnosis and treatment would be routinely done when symptoms are overt, meaning that the histopathological changes have already progressed. Therefore, we used active immunization to target pathogenic tau in 4, 8, and 18 months-old P301L tau transgenic pR5 mice that have an onset of NFT pathology at 6 months of age. In all age groups, NFT pathology was significantly reduced in treated compared to control pR5 mice. Similarly, phosphorylation of tau at pathological sites was reduced. In addition, increased astrocytosis was found in the oldest treated group. Taken together, our data suggests that tau-targeted immunization slows the progression of NFT pathology in mice, with practical implications for human patients. PMID:22174735

  17. VMD approach to {tau}{sup -}{yields}({omega},{phi}){pi}{sup -}{nu}{sub {tau}} decays

    SciTech Connect

    Falcon, D. A. Lopez; Castro, G. Lopez

    1997-03-15

    We give a description of {tau}{sup -}{yields}({omega},{phi}){pi}{sup -}{nu}{sub {tau}} decays in the approach of the vector-meson dominance (VMD) model and compare our results with the conserved vector current (CVC) predictions and experimental data.

  18. Tau, phospho-tau, and S-100B in the cerebrospinal fluid of children with multiple sclerosis.

    PubMed

    Rostasy, Kevin; Withut, Esther; Pohl, Daniela; Lange, Peter; Ciesielcyk, Barbara; Diem, Ricarda; Gärtner, Jutta; Otto, Markus

    2005-10-01

    Axonal injury and glial activation are an early neuropathologic event in adults with multiple sclerosis. To investigate whether markers of axonal injury and glial activation are already elevated in the cerebrospinal fluid of children with multiple sclerosis, we studied the cerebrospinal fluid of 25 children with multiple sclerosis and 67 controls for the presence of tau, phospho-tau, and S-100B proteins using specific enzyme-linked immunoabsorbent assays. In general, tau, phospho-tau, and S-100B protein levels did not differ significantly between groups. However, in a subgroup of nine children with multiple sclerosis, all of whom had prominent clinical symptoms at the time of lumbar puncture and radiologic disease activity, tau protein levels were significantly elevated when compared with other controls. These data indicate that axonal injury is not restricted to adult multiple sclerosis but can already occur in children with multiple sclerosis.

  19. Hadron structure in {tau}{yields}KK{pi}{nu}{sub {tau}}decays

    SciTech Connect

    Gomez Dumm, D.; Roig, P.; Pich, A.; Portoles, J.

    2010-02-01

    We analyze the hadronization structure of both vector and axial-vector currents leading to {tau}{yields}KK{pi}{nu}{sub {tau}}decays. At leading order in the 1/N{sub C} expansion, and considering only the contribution of the lightest resonances, we work out, within the framework of the resonance chiral Lagrangian, the structure of the local vertices involved in those processes. The couplings in the resonance theory are constrained by imposing the asymptotic behavior of vector and axial-vector spectral functions ruled by QCD. In this way we predict the hadron spectra and conclude that, contrary to previous assertions, the vector contribution dominates by far over the axial-vector one in all KK{pi} charge channels.

  20. Histone deacetylase 6 inhibition improves memory and reduces total tau levels in a mouse model of tau deposition

    PubMed Central

    2014-01-01

    Introduction Tau pathology is associated with a number of age-related neurodegenerative disorders. Few treatments have been demonstrated to diminish the impact of tau pathology in mouse models and none are yet effective in humans. Histone deacetylase 6 (HDAC6) is an enzyme that removes acetyl groups from cytoplasmic proteins, rather than nuclear histones. Its substrates include tubulin, heat shock protein 90 and cortactin. Tubastatin A is a selective inhibitor of HDAC6. Modification of tau pathology by specific inhibition of HDAC6 presents a potential therapeutic approach in tauopathy. Methods We treated rTg4510 mouse models of tau deposition and non-transgenic mice with tubastatin (25 mg/kg) or saline (0.9%) from 5 to 7 months of age. Cognitive behavior analysis, histology and biochemical analysis were applied to access the effect of tubastatin on memory, tau pathology and neurodegeneration (hippocampal volume). Results We present data showing that tubastatin restored memory function in rTg4510 mice and reversed a hyperactivity phenotype. We further found that tubastatin reduced the levels of total tau, both histologically and by western analysis. Reduction in total tau levels was positively correlated with memory improvement in these mice. However, there was no impact on phosphorylated forms of tau, either by histology or western analysis, nor was there an impact on silver positive inclusions histologically. Conclusion Potential mechanisms by which HDAC6 inhibitors might benefit the rTg4510 mouse include stabilization of microtubules secondary to increased tubulin acetylation, increased degradation of tau secondary to increased acetylation of HSP90 or both. These data support the use of HDAC6 inhibitors as potential therapeutic agents against tau pathology. PMID:24576665

  1. TBI-Induced Formation of Toxic Tau and Its Biochemical Similarities to Tau in AD Brains

    DTIC Science & Technology

    2016-10-01

    neurodegenerative diseases like Alzheimer’s disease or fronto-temporal lobar degeneration. DOH01-STEM5-2016-00108 (Arancio, PI) 0.96 cal mo DOH...Multiple proteins implicated in neurodegenerative diseases accumulate in axons after brain trauma in humans. Exp Neurol, 2007. 208(2): p. 185-92. 8...and Alzheimer’s disease (AD) lead to similar biochemical changes in tau that increase its toxicity and contribute to cognitive and

  2. Overexpression of Wild-Type Murine Tau Results in Progressive Tauopathy and Neurodegeneration

    PubMed Central

    Adams, Stephanie J.; Crook, Richard J.P.; DeTure, Michael; Randle, Suzanne J.; Innes, Amy E.; Yu, Xin Z.; Lin, Wen-Lang; Dugger, Brittany N.; McBride, Melinda; Hutton, Mike; Dickson, Dennis W.; McGowan, Eileen

    2009-01-01

    Here, we describe the generation and characterization of a novel tau transgenic mouse model (mTau) that overexpresses wild-type murine tau protein by twofold compared with endogenous levels. Transgenic tau expression was driven by a BAC transgene containing the entire wild-type mouse tau locus, including the endogenous promoter and the regulatory elements associated with the tau gene. The mTau model therefore differs from other tau models in that regulation of the genomic mouse transgene mimics that of the endogenous gene, including normal exon splicing regulation. Biochemical data from the mTau mice demonstrated that modest elevation of mouse tau leads to tau hyperphosphorylation at multiple pathologically relevant epitopes and accumulation of sarkosyl-insoluble tau. The mTau mice show a progressive increase in hyperphosphorylated tau pathology with age up to 15 to 18 months, which is accompanied by gliosis and vacuolization. In contrast, older mice show a decrease in tau pathology levels, which may represent hippocampal neuronal loss occurring in this wild-type model. Collectively, these results describe a novel model of tauopathy that develops pathological changes reminiscent of early stage Alzheimer’s disease and other related neurodegenerative diseases, achieved without overexpression of a mutant human tau transgene. This model will provide an important tool for understanding the early events leading to the development of tau pathology and a model for analysis of potential therapeutic targets for sporadic tauopathies. PMID:19717642

  3. The Dynamics and Turnover of Tau Aggregates in Cultured Cells: INSIGHTS INTO THERAPIES FOR TAUOPATHIES.

    PubMed

    Guo, Jing L; Buist, Arjan; Soares, Alberto; Callaerts, Kathleen; Calafate, Sara; Stevenaert, Frederik; Daniels, Joshua P; Zoll, Bryan E; Crowe, Alex; Brunden, Kurt R; Moechars, Diederik; Lee, Virginia M Y

    2016-06-17

    Filamentous tau aggregates, the hallmark lesions of Alzheimer disease (AD), play key roles in neurodegeneration. Activation of protein degradation systems has been proposed to be a potential strategy for removing pathological tau, but it remains unclear how effectively tau aggregates can be degraded by these systems. By applying our previously established cellular model system of AD-like tau aggregate induction using preformed tau fibrils, we demonstrate that tau aggregates induced in cells with regulated expression of full-length mutant tau can be gradually cleared when soluble tau expression is suppressed. This clearance is at least partially mediated by the autophagy-lysosome pathway, although both the ubiquitin-proteasome system and the autophagy-lysosome pathway are deficient in handling large tau aggregates. Importantly, residual tau aggregates left after the clearance phase leads to a rapid reinstatement of robust tau pathology once soluble tau expression is turned on again. Moreover, we succeeded in generating monoclonal cells persistently carrying tau aggregates without obvious cytotoxicity. Live imaging of GFP-tagged tau aggregates showed that tau inclusions are dynamic structures constantly undergoing "fission" and "fusion," which facilitate stable propagation of tau pathology in dividing cells. These findings provide a greater understanding of cell-to-cell transmission of tau aggregates in dividing cells and possibly neurons. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Loss of Tau results in defects in photoreceptor development and progressive neuronal degeneration in Drosophila.

    PubMed

    Bolkan, Bonnie J; Kretzschmar, Doris

    2014-12-01

    Accumulations of Tau, a microtubule-associated protein (MAP), into neurofibrillary tangles is a hallmark of Alzheimer's disease and other tauopathies. However, the mechanisms leading to this pathology are still unclear: the aggregates themselves could be toxic or the sequestration of Tau into tangles might prevent Tau from fulfilling its normal functions, thereby inducing a loss of function defect. Surprisingly, the consequences of losing normal Tau expression in vivo are still not well understood, in part due to the fact that Tau knockout mice show only subtle phenotypes, presumably due to the fact that mammals express several MAPs with partially overlapping functions. In contrast, flies express fewer MAP, with Tau being the only member of the Tau/MAP2/MAP4 family. Therefore, we used Drosophila to address the physiological consequences caused by the loss of Tau. Reducing the levels of fly Tau (dTau) ubiquitously resulted in developmental lethality, whereas deleting Tau specifically in neurons or the eye caused progressive neurodegeneration. Similarly, chromosomal mutations affecting dTau also caused progressive degeneration in both the eye and brain. Although photoreceptor cells initially developed normally in dTau knockdown animals, they subsequently degenerated during late pupal stages whereas weaker dTau alleles caused an age-dependent defect in rhabdomere structure. Expression of wild type human Tau partially rescued the neurodegenerative phenotype caused by the loss of endogenous dTau, suggesting that the functions of Tau proteins are functionally conserved from flies to humans. © 2014 Wiley Periodicals, Inc.

  5. SKIMMR: facilitating knowledge discovery in life sciences by machine-aided skim reading

    PubMed Central

    Burns, Gully A.P.C.

    2014-01-01

    Background. Unlike full reading, ‘skim-reading’ involves the process of looking quickly over information in an attempt to cover more material whilst still being able to retain a superficial view of the underlying content. Within this work, we specifically emulate this natural human activity by providing a dynamic graph-based view of entities automatically extracted from text. For the extraction, we use shallow parsing, co-occurrence analysis and semantic similarity computation techniques. Our main motivation is to assist biomedical researchers and clinicians in coping with increasingly large amounts of potentially relevant articles that are being published ongoingly in life sciences. Methods. To construct the high-level network overview of articles, we extract weighted binary statements from the text. We consider two types of these statements, co-occurrence and similarity, both organised in the same distributional representation (i.e., in a vector-space model). For the co-occurrence weights, we use point-wise mutual information that indicates the degree of non-random association between two co-occurring entities. For computing the similarity statement weights, we use cosine distance based on the relevant co-occurrence vectors. These statements are used to build fuzzy indices of terms, statements and provenance article identifiers, which support fuzzy querying and subsequent result ranking. These indexing and querying processes are then used to construct a graph-based interface for searching and browsing entity networks extracted from articles, as well as articles relevant to the networks being browsed. Last but not least, we describe a methodology for automated experimental evaluation of the presented approach. The method uses formal comparison of the graphs generated by our tool to relevant gold standards based on manually curated PubMed, TREC challenge and MeSH data. Results. We provide a web-based prototype (called ‘SKIMMR’) that generates a network of

  6. Deep photospheric flows in Tau Scorpii

    NASA Technical Reports Server (NTRS)

    Smith, M. A.; Karp, A. H.

    1979-01-01

    From analysis of weak, unblended, ultraviolet lines observed in Tau Scorpii by Copernicus, the same line widths and the same slightly blue-depressed wings as found in the upper photospheric lines of the visual region are found. In addition, a radial-velocity discrepancy of about 6 km/s between weak and strong lines in the 1000-1300-A region is found. These results are in quantitative agreement with one another and with the results of the visual region. They imply that a flow of material is present even in the deep photosphere of this star. However, one cannot yet specify the geometry of the flow (outward-radial versus temperature-weighted convection columns). At the least, this flow alters the expected radiation-driven flow solution close to the photosphere. At the most, it could provide the heating of a chromosphere or a corona just outside the photosphere, as required by the imperfect flow model.

  7. Deep photospheric flows in Tau Scorpii

    NASA Technical Reports Server (NTRS)

    Smith, M. A.; Karp, A. H.

    1979-01-01

    From analysis of weak, unblended, ultraviolet lines observed in Tau Scorpii by Copernicus, the same line widths and the same slightly blue-depressed wings as found in the upper photospheric lines of the visual region are found. In addition, a radial-velocity discrepancy of about 6 km/s between weak and strong lines in the 1000-1300-A region is found. These results are in quantitative agreement with one another and with the results of the visual region. They imply that a flow of material is present even in the deep photosphere of this star. However, one cannot yet specify the geometry of the flow (outward-radial versus temperature-weighted convection columns). At the least, this flow alters the expected radiation-driven flow solution close to the photosphere. At the most, it could provide the heating of a chromosphere or a corona just outside the photosphere, as required by the imperfect flow model.

  8. CP Violation in Tau to K* Decays

    SciTech Connect

    Hodgkinson, Mark; /Manchester U.

    2006-03-10

    A sample of {tau}{sup {+-}} {yields} K*{sup {+-}} decays with K*{sup {+-}} {yields} K{sub S}{sup 0}{pi}{sup {+-}} and K{sub S}{sup 0} {yields} {pi}{sup +}{pi}{sup -}, using 123.4 fb{sup -1} of data collected by the BaBar detector at the Stanford Linear Accelerator Center, is used to search for a direct CP violation effect in the charged Higgs sector. No evidence of CP violation is found and the imaginary part of the charged Higgs coupling, {l_brace}Im{r_brace}({Lambda}), in the Multi-Higgs-Doublet-Model is found to be at -0.284 < {l_brace}Im{r_brace}({Lambda}) < 0.200 at 90% Confidence Level. In addition the installation of the kk2f Monte Carlo generator into the BaBar software framework is described.

  9. Effect of added salt and increase in ionic strength on skim milk electroacidification performances.

    PubMed

    Bazinet, L; Ippersiel, D; Gendron, C; Mahdavi, B; Amiot, J; Lamarche, F

    2001-05-01

    Bipolar-memibrane electroacidification (BMEA) technology which uses the property of bipolar membranes to split water and the demineralization action of cation-exchange membranes (CEM), was tested for the production of acid casein. BMEA has numerous advantages in comparison with conventional isoelectric precipitation processes of proteins used in the dairy industry. BMEA uses electricity to generate the desired ionic species to acidify the treated solutions. The process can be precisely controlled, as electro-acidification rate is regulated by the effective current density in the cell. Water dissociation at the bipolar membrane interface is continuous and avoids local excess of acid. In-situ generation of dangerous chemicals (acids and bases) reduces the risks associated with the handling, transportation, use and elimination of these products. The aim of this study was to evaluate the performance of BMEA in different conditions of added ionic strength (p(added) = 0, 0.25, 0.5 and 1.0 M) and added salt (CaCl2, NaCl and KCl). The combination of KCl and p(added) = 0.5 M gave the best results with a 45% decrease in energy consumption. The increased energy efficiency was the result of a decrease in the anode/cathode voltage difference. This was due to an increase of conductivity, produced by addition of salt, necessary to compensate for the lack of sufficiently mobile ions in the skim milk. However, the addition of salts, irrespective of type or ionic strength, increased the required operation time. The protein profile of isolates were similar under all experimental conditions, except at 1.0 M-CaCl2.

  10. Short communication: Change of naturally occurring benzoic acid during skim milk fermentation by commercial cheese starters.

    PubMed

    Han, Noori; Park, Sun-Young; Kim, Sun-Young; Yoo, Mi-Young; Paik, Hyun-Dong; Lim, Sang-Dong

    2016-11-01

    This study sought to investigate the change of naturally occurring benzoic acid (BA) during skim milk fermentation by 4 kinds of commercial cheese starters used in domestic cheese. The culture was incubated at 3-h intervals for 24h at 30, 35, and 40°C. The BA content during fermentation by Streptococcus thermophilus STB-01 was detected after 12h at all temperatures, sharply increasing at 30°C. In Lactobacillus paracasei LC431, BA was detected after 9h at all temperatures, sharply increasing until 18h and decreasing after 18h at 30 and 35°C. In the case of R707 (consisting of Lactococcus lactis ssp. lactis and Lactococcus lactis ssp. cremoris), BA increased from 6h to 15h and decreased after 15h at 40°C. The BA during STB-01 and CHN-11 (1:1; mixture of S. thermophilus, Lc. lactis ssp. lactis, Lc. lactis ssp. cremoris, Lc. lactis ssp. diacetylactis, Leuconostoc mesenteroides ssp. cremoris) fermentation was detected after 3h at 35 and 40°C, sharply increasing up to 12h and decreasing after 15h at 35°C, and after 6h, increasing up to 9h at 30°C. After 3h, it steadily decreased at 40°C. The highest amount of BA was found during the fermentation by R707 at 30°C; 15h with 12.46mg/kg. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  11. The Utility of Genome Skimming for Phylogenomic Analyses as Demonstrated for Glycerid Relationships (Annelida, Glyceridae)

    PubMed Central

    Richter, Sandy; Schwarz, Francine; Hering, Lars; Böggemann, Markus; Bleidorn, Christoph

    2015-01-01

    Glyceridae (Annelida) are a group of venomous annelids distributed worldwide from intertidal to abyssal depths. To trace the evolutionary history and complexity of glycerid venom cocktails, a solid backbone phylogeny of this group is essential. We therefore aimed to reconstruct the phylogenetic relationships of these annelids using Illumina sequencing technology. We constructed whole-genome shotgun libraries for 19 glycerid specimens and 1 outgroup species (Glycinde armigera). The chosen target genes comprise 13 mitochondrial proteins, 2 ribosomal mitochondrial genes, and 4 nuclear loci (18SrRNA, 28SrRNA, ITS1, and ITS2). Based on partitioned maximum likelihood as well as Bayesian analyses of the resulting supermatrix, we were finally able to resolve a robust glycerid phylogeny and identified three clades comprising the majority of taxa. Furthermore, we detected group II introns inside the cox1 gene of two analyzed glycerid specimens, with two different insertions in one of these species. Moreover, we generated reduced data sets comprising 10 million, 4 million, and 1 million reads from the original data sets to test the influence of the sequencing depth on assembling complete mitochondrial genomes from low coverage genome data. We estimated the coverage of mitochondrial genome sequences in each data set size by mapping the filtered Illumina reads against the respective mitochondrial contigs. By comparing the contig coverage calculated in all data set sizes, we got a hint for the scalability of our genome skimming approach. This allows estimating more precisely the number of reads that are at least necessary to reconstruct complete mitochondrial genomes in Glyceridae and probably non-model organisms in general. PMID:26590213

  12. Lectin-based analysis of fucosylated glycoproteins of human skim milk during 47 days of lactation.

    PubMed

    Lis-Kuberka, Jolanta; Kątnik-Prastowska, Iwona; Berghausen-Mazur, Marta; Orczyk-Pawiłowicz, Magdalena

    2015-12-01

    Glycoproteins of human milk are multifunctional molecules, and their fucosylated variants are potentially active molecules in immunological events ensuring breastfed infants optimal development and protection against infection diseases. The expression of fucosylated glycotopes may correspond to milk maturation stages. The relative amounts of fucosylated glycotopes of human skim milk glycoproteins over the course of lactation from the 2(nd) day to the 47(th) day were analyzed in colostrums, transitional and mature milk samples of 43 healthy mothers by lectin-blotting using α1-2-, α1-6-, and α1-3-fucose specific biotinylated Ulex europaeus (UEA), Lens culinaris (LCA), and Lotus tetragonolobus (LTA) lectins, respectively. The reactivities of UEA and LCA with the milk glycoproteins showed the highest expression of α1-2- and α1-6-fucosylated glycotopes on colostrum glycoproteins. The level of UEA-reactive glycoproteins from the beginning of lactation to the 14(th) day was high and relatively stable in contrast to LCA-reactive glycoproteins, the level of which significantly decreased from 2-3 to 7-8 days then remained almost unchanged until the 12(th)-14(th) days. Next, during the progression of lactation the reactivities with both lectins declined significantly. Eighty percent of α1-2- and/or α1-6-fucosylated glycoproteins showed a high negative correlation with milk maturation. In contrast, most of the analyzed milk glycoproteins were not recognized or weakly recognized by LTA and remained at a low unchanged level over lactation. Only a 30-kDa milk glycoprotein was evidently LTA-reactive, showing a negative correlation with milk maturation. The gradual decline of high expression of α1-2- and α1-6-, but not α1-3-, fucoses on human milk glycoproteins of healthy mothers over lactation was associated with milk maturation.

  13. Parents' and children's acceptance of skim chocolate milks sweetened by monk fruit and stevia leaf extracts.

    PubMed

    Li, X E; Lopetcharat, K; Drake, M A

    2015-05-01

    Chocolate milk increases milk consumption of children, but high sugar content raises health concerns. Interest in sugar reduction and parents' preference for natural sweeteners necessitates further research on natural nonnutritive sweeteners. However, it is important to maintain consumer acceptability, especially for children, while reducing sugar in chocolate milk. The objectives of this study were to identify the sweetness intensity perception of stevia leaf (STV) and monk fruit (MK) extracts in skim chocolate milk (SCM), to evaluate STV and MK as the sole or partial sweetener source for SCM for young adults (19 to 35 y) and children (5 to 13 y), and to determine if information on natural nonnutritive sweeteners impacted parents' acceptability of SCM. Power function and 2-alternative forced choice studies were used to determine the iso-sweetness of nonnutritive sweeteners to a sucrose control in SCM (51.4 g/L, SUC control). Young adults (n = 131) evaluated 9 different SCM (SUC control, STV, MK, STV:sucrose blends, or MK:sucrose blends) in a completely randomized 2-d test. Children (n = 167) evaluated SUC control SCM and SCM with 39.7 g/L sucrose and 46 mg/L MK (MK25) or 30 mg/L STV (STV25). Parents evaluated SUC control, MK25, and STV25 in a balanced crossover design with a 40-d wait time between primed or unprimed ballots. Chocolate milks solely sweetened by nonnutritive sweeteners were less acceptable compared with SUC control by young adults. MK25 and STV25 were acceptable by young adults and children. The presentation of chocolate milk label information had different effects on parental acceptance. Traditional parents preferred sucrose sweetened SCM, and label conscious parents preferred SCM with natural nonnutritive sweeteners.

  14. The Utility of Genome Skimming for Phylogenomic Analyses as Demonstrated for Glycerid Relationships (Annelida, Glyceridae).

    PubMed

    Richter, Sandy; Schwarz, Francine; Hering, Lars; Böggemann, Markus; Bleidorn, Christoph

    2015-11-19

    Glyceridae (Annelida) are a group of venomous annelids distributed worldwide from intertidal to abyssal depths. To trace the evolutionary history and complexity of glycerid venom cocktails, a solid backbone phylogeny of this group is essential. We therefore aimed to reconstruct the phylogenetic relationships of these annelids using Illumina sequencing technology. We constructed whole-genome shotgun libraries for 19 glycerid specimens and 1 outgroup species (Glycinde armigera). The chosen target genes comprise 13 mitochondrial proteins, 2 ribosomal mitochondrial genes, and 4 nuclear loci (18SrRNA, 28SrRNA, ITS1, and ITS2). Based on partitioned maximum likelihood as well as Bayesian analyses of the resulting supermatrix, we were finally able to resolve a robust glycerid phylogeny and identified three clades comprising the majority of taxa. Furthermore, we detected group II introns inside the cox1 gene of two analyzed glycerid specimens, with two different insertions in one of these species. Moreover, we generated reduced data sets comprising 10 million, 4 million, and 1 million reads from the original data sets to test the influence of the sequencing depth on assembling complete mitochondrial genomes from low coverage genome data. We estimated the coverage of mitochondrial genome sequences in each data set size by mapping the filtered Illumina reads against the respective mitochondrial contigs. By comparing the contig coverage calculated in all data set sizes, we got a hint for the scalability of our genome skimming approach. This allows estimating more precisely the number of reads that are at least necessary to reconstruct complete mitochondrial genomes in Glyceridae and probably non-model organisms in general.

  15. Regulatable transgenic mouse models of Alzheimer disease: onset, reversibility and spreading of Tau pathology.

    PubMed

    Hochgräfe, Katja; Sydow, Astrid; Mandelkow, Eva-Maria

    2013-09-01

    Accumulation of amyloidogenic proteins such as Tau is a hallmark of neurodegenerative diseases including Alzheimer disease and fronto-temporal dementias. To link Tau pathology to cognitive impairments and defects in synaptic plasticity, we created four inducible Tau transgenic mouse models with expression of pro- and anti-aggregant variants of either full-length human Tau (hTau40/ΔK280 and hTau40/ΔK280/PP) or the truncated Tau repeat domain (Tau(RD)/ΔK280 and Tau(RD)/ΔK280/PP). Here we review the histopathological features caused by pro-aggregant Tau, and correlate them with behavioral deficits and impairments in synaptic transmission. Both pro-aggregant Tau variants cause Alzheimer-like features, including synapse loss, mis-localization of Tau into the somatodendritic compartment, conformational changes and hyperphosphorylation. However, there is a clear difference in the extent of Tau aggregation and neurotoxicity. While pro-aggregant full-length hTau40/ΔK280 leads to a 'pre-tangle' pathology, the repeat domain Tau(RD)/ΔK280 causes massive formation of neurofibrillary tangles and neuronal loss in the hippocampus. However, both Tau variants cause co-aggregation of human and mouse Tau and similar functional impairments. Thus, earlier Tau pathological stages and not necessarily neurofibrillary tangles are critical for the development of cognitive malfunctions. Most importantly, memory and synapses recover after switching off expression of pro-aggregant Tau. The rescue of functional impairments correlates with the rescue of most Tau pathological changes and most strikingly the recovery of synapses. This implies that tauopathies as such are reversible, provided that amyloidogenic Tau is removed. Therefore, our Tau transgenic mice may serve as model systems for in vivo validation of therapeutic strategies and drug candidates with regard to cognition and synaptic function. © 2013 The Authors Journal compilation © 2013 FEBS.

  16. First measurement of sigma (p anti-p ---> Z) . Br (Z ---> tau tau) at s**(1/2) = 1.96- TeV

    SciTech Connect

    Abazov, V.M.; Abbott, B.; Abolins, M.; Acharya, B.S.; Adams, M.; Adams, T.; Agelou, M.; Agram, J.-L.; Ahn, S.H.; Ahsan, M.; Alexeev, G.D.; Alkhazov, G.; Alton, A.; Alverson, G.; Alves, G.A.; Anastasoaie, M.; Andeen, T.; Anderson, S.; Andrieu, B.; Arnoud, Y.; Askew, A.; /Buenos Aires U. /Rio de Janeiro, CBPF /Rio de Janeiro State U. /Sao Paulo, IFT /Alberta U. /Simon Fraser U. /York U., Canada /McGill U. /Beijing, Inst. High Energy Phys. /Andes U., Bogota /Charles U. /Prague, Tech. U. /Prague, Inst. Phys. /San Francisco de Quito U. /Clermont-Ferrand U. /LPSC, Grenoble /Marseille, CPPM /Orsay, LAL /Paris U., VI-VII /DAPNIA, Saclay /Strasbourg, IReS

    2004-12-01

    The authors present a measurement of the cross section for Z production times the branching fraction to {tau} leptons, {sigma} {center_dot} Br(Z {yields} {tau}{sup +}{tau}{sup -}), in p{bar p} collisions at {radical}s = 1.96 TeV in the channel in which one {tau} decays into {mu}{nu}{sub {mu}}{nu}{sub {tau}}, and the other into hadrons + {nu}{sub {tau}} or e{nu}{sub e}{nu}{sub {tau}}. The data sample corresponds to an integrated luminosity of 226 pb{sup -1} collected with the D0 detector at the Fermilab Tevatron collider. The final sample contains 2008 candidate events with an estimated background of 55%. From this they obtain {sigma} {center_dot} Br(Z {yields} {tau}{sup +}{tau}{sup -}) = 237 {+-} 15(stat) {+-} 18(sys) {+-} 15(lum) pb, in agreement with the standard model prediction.

  17. Measurement of the tau- to eta pi-pi+pi-nu tau Branching Fraction and a Search for a Second-Class Current in the tau- to eta'(958)pi-nu tau Decay

    SciTech Connect

    Aubert, B.; Bona, M.; Boutigny, D.; Karyotakis, Y.; Lees, J.P.; Poireau, V.; Prudent, X.; Tisserand, V.; Zghiche, A.; Garra Tico, J.; Grauges, E.; Lopez, L.; Palano, A.; Pappagallo, M.; Eigen, G.; Stugu, B.; Sun, L.; Abrams, G.S.; Battaglia, M.; Brown, David Nathan; Button-Shafer, J.; /LBL, Berkeley /UC, Berkeley /Birmingham U. /Ruhr U., Bochum /Bristol U. /British Columbia U. /Brunel U. /Novosibirsk, IYF /UC, Irvine /UCLA /UC, Riverside /UC, San Diego /UC, Santa Barbara /UC, Santa Cruz /Caltech /Cincinnati U. /Colorado U. /Colorado State U. /Dortmund U. /Dresden, Tech. U. /Ecole Polytechnique /Edinburgh U. /Ferrara U. /Frascati /Genoa U. /Harvard U. /Heidelberg U. /Imperial Coll., London /Iowa U. /Iowa State U. /Johns Hopkins U. /Karlsruhe U. /Orsay, LAL /LLNL, Livermore /Liverpool U. /Queen Mary, U. of London /Royal Holloway, U. of London /Louisville U. /Manchester U. /Maryland U. /Massachusetts U., Amherst /MIT, LNS /McGill U. /Milan U. /INFN, Milan /Mississippi U. /Montreal U. /Mt. Holyoke Coll. /Naples U. /NIKHEF, Amsterdam /Notre Dame U. /Ohio State U. /Oregon U. /Padua U. /Paris U., VI-VII /Pennsylvania U. /Perugia U. /Pisa U. /Princeton U. /INFN, Rome /Rostock U. /Rutherford /DSM, DAPNIA, Saclay /South Carolina U. /SLAC /Stanford U., Phys. Dept. /SUNY, Albany /Tennessee U. /Texas U. /Texas U., Dallas /Turin U. /INFN, Turin /Trieste U. /Valencia U., IFIC /Victoria U. /Warwick U. /Wisconsin U., Madison /Yale U.

    2008-03-24

    The {tau}{sup -} {yields} {eta}{pi}{sup -}{pi}{sup +}{pi}{sup -}{nu}{sub {tau}} decay with the {eta} {yields} {gamma}{gamma} mode is studied using 384 fb{sup -1} of data collected by the BABAR detector. The branching fraction is measured to be (1.60 {+-} 0.05 {+-} 0.11) x 10{sup -4}. It is found that {tau}{sup -} {yields} f{sub 1}(1285){pi}{sup -} {nu}{sub {tau}} {yields} {eta}{pi}{sup -}{pi}{sup +}{pi}{sup -}{nu}{sub {tau}} is the dominant decay mode with a branching fraction of (1.11 {+-} 0.06 {+-} 0.05) x 10{sup -4}. The first error on the branching fractions is statistical and the second systematic. In addition, a 90% confidence level upper limit on the branching fraction of the {tau}{sup -} {yields} {eta}{prime}(958){pi}{sup -}{nu}{sub {tau}} decay is measured to be 7.2 x 10{sup -6}. This last decay proceeds through a second-class current and is expected to be forbidden in the limit of isospin symmetry.

  18. Early Axonopathy Preceding Neurofibrillary Tangles in Mutant Tau Transgenic Mice

    PubMed Central

    Leroy, Karelle; Bretteville, Alexis; Schindowski, Katharina; Gilissen, Emmanuel; Authelet, Michèle; De Decker, Robert; Yilmaz, Zehra; Buée, Luc; Brion, Jean-Pierre

    2007-01-01

    Neurodegenerative diseases characterized by brain and spinal cord involvement often show widespread accumulations of tau aggregates. We have generated a transgenic mouse line (Tg30tau) expressing in the forebrain and the spinal cord a human tau protein bearing two pathogenic mutations (P301S and G272V). These mice developed age-dependent brain and hippocampal atrophy, central and peripheral axonopathy, progressive motor impairment with neurogenic muscle atrophy, and neurofibrillary tangles and had decreased survival. Axonal spheroids and axonal atrophy developed early before neurofibrillary tangles. Neurofibrillary inclusions developed in neurons at 3 months and were of two types, suggestive of a selective vulnerability of neurons to form different types of fibrillary aggregates. A first type of tau-positive neurofibrillary tangles, more abundant in the forebrain, were composed of ribbon-like 19-nm-wide filaments and twisted paired helical filaments. A second type of tau and neurofilament-positive neurofibrillary tangles, more abundant in the spinal cord and the brainstem, were composed of 10-nm-wide neurofilaments and straight 19-nm filaments. Unbiased stereological analysis indicated that total number of pyramidal neurons and density of neurons in the lumbar spinal cord were not reduced up to 12 months in Tg30tau mice. This Tg30tau model thus provides evidence that axonopathy precedes tangle formation and that both lesions can be dissociated from overt neuronal loss in selected brain areas but not from neuronal dysfunction. PMID:17690183

  19. Endogenous Aβ causes cell death via early tau hyperphosphorylation.

    PubMed

    Amadoro, G; Corsetti, V; Ciotti, M T; Florenzano, F; Capsoni, S; Amato, G; Calissano, P

    2011-06-01

    Alzheimer's disease (AD) is characterized by Aβ overproduction and tau hyperphosphorylation. We report that an early, transient and site-specific AD-like tau hyperphosphorylation at Ser262 and Thr231 epitopes is temporally and causally related with an activation of the endogenous amyloidogenic pathway that we previously reported in hippocampal neurons undergoing cell death upon NGF withdrawal [Matrone, C., Ciotti, M.T., Mercanti, D., Marolda, R., Calissano, P., 2008b. NGF and BDNF signaling control amyloidogenic route and Ab production in hippocampal neurons. Proc. Natl. Acad. Sci. 105, 13138-13143]. Such tau hyperphosphorylation, as well as apoptotic death, is (i) blocked by 4G8 and 6E10 Aβ antibodies or by specific β and/or γ-secretases inhibitors; (ii) temporally precedes tau cleavage mediated by a delayed (6-12h after NGF withdrawal) activation of caspase-3 and calpain-I; (iii) under control of Akt-GSK3β-mediated signaling. Finally, we show that such site-specific tau hyperphosphorylation causes tau detachment from microtubules and an impairment of mitochondrial trafficking. These results depict, for the first time, a rapid interplay between endogenous Aβ and tau post-translational modifications which act co-ordinately to compromise neuronal functions in the same neuronal system, under physiological conditions as seen in AD brain. Copyright © 2009 Elsevier Inc. All rights reserved.

  20. PHOSPHORYLATED TAU: TOXIC, PROTECTIVE, OR NONE OF THE ABOVE

    PubMed Central

    Castellani, Rudy J.; Nunomura, Akihiko; Lee, Hyoung-gon; Perry, George; Smith, Mark A.

    2009-01-01

    Identification of phosphorylated tau as the major protein component of neurofibrillary tangles (NFTs) led to the concept that phosphorylated tau was inherently toxic and, as such, intimately involved in Alzheimer’s disease (AD) pathogenesis. While superficially logical, this construct ignores a number of key findings in AD, including i) that NFTs are encountered in viable neurons until late stage disease; ii) that NFTs persist within the neuronal cytoplasm for decades; iii) that NFTs are encountered, sometimes in significant numbers, in cognitively intact elderly; and iv) that neurons with NFTs contain normal content and structure of microtubules. Experimental data in transgenic animal models has further demonstrated that NFTs accumulate in neurons in spite of tau suppression and behavior normalization. These data call into question the inherent toxicity of phosphorylated tau, seemingly leaving the only viable hypothesis of the ad hoc “toxic intermediate” phosphorylated tau concept. However, since we also know that phosphorylated tau sequesters redox active heavy metals and protects against oxidative stress, here we suggest that phosphorylated tau serves a protective role against cellular toxicity. PMID:18688087

  1. Lepton flavor violating {tau} and B decays and heavy neutrinos

    SciTech Connect

    He Xiaogang

    2004-12-01

    We study lepton flavor violating (LFV) {tau} and B decays in models with heavy neutrinos to constrain the mixing matrix parameters U{sub {tau}}{sub N}. We find that the best current constraints when the heavy neutrinos are purely left handed come from LFV radiative {tau} decay modes. To obtain competitive constraints in LFV B decay, it is necessary to probe b{yields}X{sub s}{tau}{sup {+-}}e{sup {+-}} at the 10{sup -7} level. When the heavy neutrinos have both left- and right-handed couplings, the mixing parameters can be constrained by studying LFV B decay modes and LFV {tau} decay into three charged leptons. We find that the branching ratios B({tau}{sup {+-}}{yields}l{sub 1}{sup {+-}}l{sub 2}{sup {+-}}l{sub 3}{sup {+-}}), B(B{sub s}{yields}{tau}{sup {+-}}e{sup {+-}}) and B(b{yields}X{sub s}l{sub 1}{sup {+-}}l{sub 2}{sup {+-}}) need to be probed at the 10{sup -8} level in order to constrain the mixing parameters beyond what is known from unitarity.

  2. Measurement of the Tau- to F1(1285) Pi- Nu/Tau Branching Fraction And a Search for Second-Class Currents in Tau to Eta-Prime(958) Pi- Nu/Tau

    SciTech Connect

    Alwyn, K.E.; /Manchester U.

    2011-12-01

    The {tau}{sup -} {yields} {eta}{pi}{sup -}{pi}+{pi}{sup -}{nu}{tau} decay with the {eta} {yields} {gamma}{gamma} mode is studied using 384 fb{sup -1} of data collected by the BaBar detector. The branching fraction is measured to be (1.60 {+-} 0.05 {+-} 0.11) x 10{sup -4}. It is found that {tau}{sup -} {yields} f1(1285){pi}{sup -}{nu}{tau} {yields} {eta}{pi}{sup -}{pi}+{pi}{sup -}{nu}{tau} is the dominant decay mode with a branching fraction of (1.11 {+-} 0.06 {+-} 0.05) x 10{sup -4}. The first error is statistical and the second systematic. In addition, a 90% confidence level upper limit on the branching fraction of the {tau}{sup -} {yields} {eta}{prime}(958){pi}{sup -}{nu}{tau} decay is measured to be 7.2 x 10{sup -6}. This last decay proceeds through a second-class current and is expected to be forbidden in the limit of isospin symmetry.

  3. Measuring the Higgs Boson's Parity Using tau -> rho nu

    SciTech Connect

    Bower, Gary

    2002-08-08

    We present a very promising method for a measurement of the Higgs boson parity using the H/A {yields} {tau}{sup +}{tau}{sup -} {yields} {rho}{sup +}{bar {nu}}{sub {tau}}{rho}{sup -}{nu}{sub {tau}} {yields} {pi}{sup +}{pi}{sup 0} {bar {nu}}{sub {tau}} {pi}{sup -}{pi}{sup 0} {nu}{sub {tau}} decay chain. The method is both model independent and independent of the Higgs production mechanism. Angular distributions of the {tau} decay products which are sensitive to the Higgs boson parity are defined and are found to be measurable using typical properties of a future detector for an e{sup +}e{sup -} linear collider. The prospects for the measurement of the parity of a Higgs boson with a mass of 120 GeV are quantified for the case of e{sup +}e{sup -} collisions of 500 GeV center of mass energy with an integrated luminosity of 500fb{sup -1}. The Standard Model Higgsstrahlung production process is used as an example.

  4. Effects of macromolecular crowding and osmolyte on human Tau fibrillation.

    PubMed

    Wu, Yingying; Teng, Ningning; Li, Sen

    2016-09-01

    Tau fibrillation is reported to be involved in neurodegenerative disorders, such as Alzheimer's disease, in which the natural environment is very crowded in the cells. Understanding the role of crowding environments in regulating Tau fibrillation is of great importance for elucidating the etiology of these diseases. In this experiment, the effects of macromolecular crowding and osmolyte reagents in the crowding environment on Tau fibrillation were studied by thioflavin T binding, SDS-PAGE and TEM assays. Ficoll 70 and Dextran 70 of different concentrations were used as macromolecular crowding reagents inside the cells and showed a strong enhancing effect on the fibrillation of normal and hyperphosphorylated Tau. The enhancing effect of Dextran is stronger than that of Ficoll 70 at the same concentration. In addition, the cellular osmolyte sucrose was found to protect Tau against fibrillation, and inhibit the enhancing effect of macromolecular crowding on Tau fibrillation. A possible model for the fibrillation process of Tau and the effect of macromolecular crowding and osmolyte on this process was proposed based on these experimental results. The information obtained from our study can enhance the understanding of how proteins aggregate and avoid aggregation in crowded physiological environments and might lead to a better understanding of the molecular mechanisms of Alzheimer's disease in vivo.

  5. Mechanisms of Tau and Aβ-induced Excitotoxicity

    PubMed Central

    Pallo, Susanne P.; DiMaio, John; Cook, Alexis; Nilsson, Bradley; Johnson, Gail V.W.

    2016-01-01

    Excitotoxicity was originally postulated to be a late stage side effect of Alzheimer’s disease (AD)-related neurodegeneration, however more recent studies indicate that it may occur early in AD and contribute to the neurodegenerative process. Tau and amyloid beta (Aβ), the main components of neurofibrillary tangles (NFTs) and amyloid plaques, have been implicated in cooperatively and independently facilitating excitotoxicity. Our study investigated the roles of tau and Aβ in AD-related excitotoxicity. In vivo studies showed that tau knockout (tau−/−) mice were significantly protected from seizures and hippocampal superoxide production induced with the glutamate analog, kainic acid (KA). We hypothesized that tau accomplished this by facilitating KA-induced Ca2+ influx into neurons, however lentiviral tau knockdown failed to ameliorate KA-induced Ca2+ influx into primary rat cortical neurons. We further investigated if tau cooperated with Aβ to facilitate KA-induced Ca2+ influx. While Aβ biphasically modulated the KA-induced Ca2+cyt responses, tau knockdown continued to have no effect. Therefore, tau facilitates KA-induced seizures and superoxide production in a manner that does not involve facilitation of Ca2+ influx through KA receptors (KAR). On the other hand, acute pretreatment with Aβ (10 minutes) enhanced KA-induced Ca2+ influx, while chronic Aβ (24 hours) significantly reduced it, regardless of tau knockdown. Given previously published connections between Aβ, group 1 metabotropic glutamate receptors (mGluRs), and KAR regulation, we hypothesized that Aβ modulates KAR via a G-protein coupled receptor pathway mediated by group 1 mGluRs. We found that Aβ did not activate group 1 mGluRs and inhibition of these receptors did not reverse Aβ modulation of KA-induced Ca2+ influx. Therefore, A