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81 results on '"M., Fagiolini"'

1. Very high energy gamma-ray observations of strong flaring activity in M87 in 2008 February

Author: J. Albert, E. Aliu, H. Anderhub, L. A. Antonelli, P. Antoranz, M. Backes, C. Baixeras, J. A. Barrio, H. Bartko, D. Bastieri, J. K. Becker, W. Bednarek, K. Berger, E. Bernardini, C. Bigongiari, A. Biland, R. K. Bock, G. Bonnoli, P. Bordas, V. Bosch-Ramon, T. Bretz, I. Britvitch, M. Camara, E. Carmona, A. Chilingarian, S. Commichau, J. L. Contreras, J. Cortina, M. T. Costado, S. Covino, V. Curtef, F. Dazzi, A. De Angelis, E. De Cea del Pozo, R. de los Reyes, B. De Lotto, M. De Maria, F. De Sabata, C. Delgado Mendez, A. Dominguez, D. Dorner, M. Doro, M. Errando, M. Fagiolini, D. Ferenc, E. Fernández, R. Firpo, M. V. Fonseca, L. Font, N. Galante, R. J. García López, M. Garczarczyk, M. Gaug, F. Goebel, M. Hayashida, A. Herrero, D. Höhne, J. Hose, C. C. Hsu, S. Huber, T. Jogler, D. Kranich, A. La Barbera, A. Laille, E. Leonardo, E. Lindfors, S. Lombardi, F. Longo, M. López, E. Lorenz, P. Majumdar, G. Maneva, N. Mankuzhiyil, K. Mannheim, L. Maraschi, M. Mariotti, M. Martínez, D. Mazin, M. Meucci, M. Meyer, J. M. Miranda, R. Mirzoyan, S. Mizobuchi, M. Moles, A. Moralejo, D. Nieto, K. Nilsson, J. Ninkovic, N. Otte, I. Oya, M. Panniello, R. Paoletti, J. M. Paredes, M. Pasanen, D. Pascoli, F. Pauss, R. G. Pegna, M. A. Perez-Torres, M. Persic, L. Peruzzo, A. Piccioli, F. Prada, E. Prandini, N. Puchades, A. Raymers, W. Rhode, M. Ribó, J. Rico, M. Rissi, A. Robert, S. Rügamer, A. Saggion, T. Y. Saito, M. Salvati, M. Sanchez-Conde, P. Sartori, K. Satalecka, V. Scalzotto, V. Scapin, T. Schweizer, M. Shayduk, K. Shinozaki, S. N. Shore, N. Sidro, A. Sierpowska-Bartosik, A. Sillanpää, D. Sobczynska, F. Spanier, A. Stamerra, L. S. Stark, L. Takalo, F. Tavecchio, P. Temnikov, D. Tescaro, M. Teshima, M. Tluczykont, D. F. Torres, N. Turini, H. Vankov, A. Venturini, V. Vitale, R. M. Wagner, W. Wittek, V. Zabalza, F. Zandanel, R. Zanin, J. Zapatero, Universitat de Barcelona, J., Albert, E., Aliu, H., Anderhub, L. A., Antonelli, P., Antoranz, M., Backe, C., Baixera, J. A., Barrio, H., Bartko, D., Bastieri, J. K., Becker, W., Bednarek, K., Berger, E., Bernardini, C., Bigongiari, A., Biland, R. K., Bock, G., Bonnoli, P., Borda, V., Bosch Ramon, T., Bretz, I., Britvitch, M., Camara, E., Carmona, A., Chilingarian, S., Commichau, J. L., Contrera, J., Cortina, M. T., Costado, S., Covino, V., Curtef, F., Dazzi, A. D., Angeli, E. D., del Pozo, R. D. L., Reye, B. D., Lotto, M. D., Maria, F. D., Sabata, C. D., Mendez, A., Dominguez, D., Dorner, M., Doro, M., Errando, M., Fagiolini, D., Ferenc, E., Fernandez, R., Firpo, M. V., Fonseca, L., Font, N., Galante, R. J. G., Lopez, M., Garczarczyk, M., Gaug, F., Goebel, M., Hayashida, A., Herrero, D., Hohne, J., Hose, C. C., Hsu, S., Huber, T., Jogler, D., Kranich, A. L., Barbera, A., Laille, E., Leonardo, E., Lindfor, S., Lombardi, Longo, Francesco, M., Lopez, E., Lorenz, P., Majumdar, G., Maneva, N., Mankuzhiyil, K., Mannheim, L., Maraschi, M., Mariotti, M., Martinez, D., Mazin, M., Meucci, M., Meyer, J. M., Miranda, R., Mirzoyan, S., Mizobuchi, M., Mole, A., Moralejo, D., Nieto, K., Nilsson, J., Ninkovic, N., Otte, I., Oya, M., Panniello, R., Paoletti, J. M., Parede, M., Pasanen, D., Pascoli, F., Pau, R. G., Pegna, M. A., Perez Torre, M., Persic, L., Peruzzo, A., Piccioli, F., Prada, E., Prandini, N., Puchade, A., Raymer, W., Rhode, M., Ribo, J., Rico, M., Rissi, A., Robert, S., Rugamer, A., Saggion, T. Y., Saito, M., Salvati, M., Sanchez Conde, P., Sartori, K., Satalecka, V., Scalzotto, V., Scapin, T., Schweizer, M., Shayduk, K., Shinozaki, S. N., Shore, N., Sidro, A., Sierpowska Bartosik, A., Sillanpaa, D., Sobczynska, F., Spanier, A., Stamerra, L. S., Stark, L., Takalo, F., Tavecchio, P., Temnikov, D., Tescaro, M., Teshima, M., Tluczykont, D. F., Torre, N., Turini, H., Vankov, A., Venturini, V., Vitale, R. M., Wagner, W., Wittek, V., Zabalza, F., Zandanel, R., Zanin, and J., Zapatero
Subjects: Photon, Radio galaxy, Astrophysics::High Energy Astrophysical Phenomena, galaxies: active, FOS: Physical sciences, Flux, Astrophysics, Astrophysics::Cosmology and Extragalactic Astrophysics, galaxies: individual: M 87, law.invention, gamma rays, Gamma Rays: Observations, Raigs gamma, law, Radio Galaxies, Radio Galaxie, Blazar, Physics, Very High Energy Gamma-ray Astronomy, MAGIC telescope, Astrophysics (astro-ph), Gamma rays, Gamma ray, Astronomy and Astrophysics, Galaxies, Monitoring program, Galàxies, Crab Nebula, Space and Planetary Science, Electrónica, Física nuclear, Electricidad, Flare
Abstract: M87 is the only known non blazar radio galaxy to emit very high energy (VHE) gamma-rays. During a monitoring program of M87, a rapid flare in VHE gamma-rays was detected by the MAGIC telescope in early 2008. The flux was found to be variable above 350 GeV on a timescale as short as 1 day at a significance level of $5.6\sigma$. The highest measured flux reached 15% of the Crab Nebula flux. We observed several substantial changes of the flux level during the 13 day observing period. The flux at lower energies (150 -- 350 GeV), instead, is compatible with being constant. The energy spectrum can be described by a power law with a photon index of $2.30 \pm 0.11_\mathrm{stat} \pm 0.20_\mathrm{syst}$. The observed day-scale flux variability at VHE prefers the M87 core as source of the emission and implies that either the emission region is very compact (just a few Schwarzschild radii) or the Doppler factor of the emitting blob is rather large in the case of a non expanding emission region., Comment: 4 pages, 4 figures, small changes to fit the ApJL version
Published: 2008

2. Discovery of very high energy gamma-ray emission from the low-frequency peaked BL Lacertae object BL Lacertae

Author: J. Albert, E. Aliu, H. Anderhub, P. Antoranz, A. Armada, C. Baixeras, J. A. Barrio, H. Bartko, D. Bastieri, J. K. Becker, W. Bednarek, K. Berger, C. Bigongiari, A. Biland, R. K. Bock, P. Bordas, V. Bosch Ramon, T. Bretz, I. Britvitch, M. Camara, E. Carmona, A. Chilingarian, J. A. Coarasa, S. Commichau, J. L. Contreras, J. Cortina, M. T. Costado, V. Curtef, V. Danielyan, F. Dazzi, A. D. Angelis, C. Delgado, R. D. L. Reyes, B. D. Lotto, E. Domingo Santamaria, D. Dorner, M. Doro, M. Errando, M. Fagiolini, D. Ferenc, E. Fernandez, R. Firpo, J. Flix, M. V. Fonseca, L. Font, M. Fuchs, N. Galante, R. Garcia Lopez, M. Garczarczyk, M. Gaug, M. Giller, F. Goebel, D. Hakobyan, M. Hayashida, T. Hengstebeck, A. Herrero, D. Hohne, J. Hose, C. C. Hsu, P. Jacon, T. Jogler, R. Kosyra, D. Kranich, R. Kritzer, A. Laille, E. Lindfors, S. Lombardi, J. Lopez, M. Lopez, E. Lorenz, P. Majumdar, G. Maneva, K. Mannheim, O. Mansutti, M. Mariotti, M. Martinez, D. Mazin, C. Merck, M. Meucci, M. Meyer, J. M. Miranda, R. Mirzoyan, S. Mizobuchi, A. Moralejo, K. Nilsson, J. Ninkovic, E. Ona Wilhelmi, N. Otte, I. Oya, D. Paneque, M. Panniello, R. Paoletti, J. M. Paredes, M. Pasanen, D. Pascoli, F. Pauss, R. Pegna, M. Persic, L. Peruzzo, A. Piccioli, M. Poller, E. Prandini, N. Puchades, A. Raymers, W. Rhode, M. Ribo, J. Rico, M. Rissi, A. Robert, S. Rugamer, A. Saggion, A. Sanchez, P. Sartori, V. Scalzotto, V. Scapin, R. Schmitt, T. Schweizer, M. Shayduk, K. Shinozaki, S. N. Shore, N. Sidro, A. Sillanpaa, D. Sobczynska, A. Stamerra, L. S. Stark, L. Takalo, P. Temnikov, D. Tescaro, M. Teshima, N. Tonello, D. F. Torres, N. Turini, H. Vankov, V. Vitale, R. M. Wagner, T. Wibig, W. Wittek, F. Zandanel, R. Zanin, J. Zapatero, LONGO, FRANCESCO, J., Albert, E., Aliu, H., Anderhub, P., Antoranz, A., Armada, C., Baixera, J. A., Barrio, H., Bartko, D., Bastieri, J. K., Becker, W., Bednarek, K., Berger, C., Bigongiari, A., Biland, R. K., Bock, P., Borda, V., Bosch Ramon, T., Bretz, I., Britvitch, M., Camara, E., Carmona, A., Chilingarian, J. A., Coarasa, S., Commichau, J. L., Contrera, J., Cortina, M. T., Costado, V., Curtef, V., Danielyan, F., Dazzi, A. D., Angeli, C., Delgado, R. D. L., Reye, B. D., Lotto, E., Domingo Santamaria, D., Dorner, M., Doro, M., Errando, M., Fagiolini, D., Ferenc, E., Fernandez, R., Firpo, J., Flix, M. V., Fonseca, L., Font, M., Fuch, N., Galante, R., Garcia Lopez, M., Garczarczyk, M., Gaug, M., Giller, F., Goebel, D., Hakobyan, M., Hayashida, T., Hengstebeck, A., Herrero, D., Hohne, J., Hose, C. C., Hsu, P., Jacon, T., Jogler, R., Kosyra, D., Kranich, R., Kritzer, A., Laille, E., Lindfor, S., Lombardi, Longo, Francesco, J., Lopez, M., Lopez, E., Lorenz, P., Majumdar, G., Maneva, K., Mannheim, O., Mansutti, M., Mariotti, M., Martinez, D., Mazin, C., Merck, M., Meucci, M., Meyer, J. M., Miranda, R., Mirzoyan, S., Mizobuchi, A., Moralejo, K., Nilsson, J., Ninkovic, E., Ona Wilhelmi, N., Otte, I., Oya, D., Paneque, M., Panniello, R., Paoletti, J. M., Parede, M., Pasanen, D., Pascoli, F., Pau, R., Pegna, M., Persic, L., Peruzzo, A., Piccioli, M., Poller, E., Prandini, N., Puchade, A., Raymer, W., Rhode, M., Ribo, J., Rico, M., Rissi, A., Robert, S., Rugamer, A., Saggion, A., Sanchez, P., Sartori, V., Scalzotto, V., Scapin, R., Schmitt, T., Schweizer, M., Shayduk, K., Shinozaki, S. N., Shore, N., Sidro, A., Sillanpaa, D., Sobczynska, A., Stamerra, L. S., Stark, L., Takalo, P., Temnikov, D., Tescaro, M., Teshima, N., Tonello, D. F., Torre, N., Turini, H., Vankov, V., Vitale, R. M., Wagner, T., Wibig, W., Wittek, F., Zandanel, R., Zanin, and J., Zapatero
Subjects: High energy, Photon, Flux, FOS: Physical sciences, Astrophysics, Low frequency, Observacions astronòmiques, Gamma ray astronomy, Galaxies: individual: BL Lacertae, Astronomia de raigs gamma, MAGIC (telescope), Physics, Astrophysics (astro-ph), Gamma ray, Astronomy and Astrophysics, Active Galactic Nuclei, Light curve, MAGIC telescope, Space and Planetary Science, Very High Energy Gamma-ray Astronomy, Electrónica, Física nuclear, Electricidad, BL Lac object, Astronomical observations
Abstract: The MAGIC collaboration observed BL Lacertae for 22.2 hr during 2005 August to December and for 26 hr during 2006 July to September. The source is the historical prototype and eponym of a class of low-frequency peaked BL Lacertae (LBL) objects. A very high energy (VHE) gamma-ray signal was discovered with a 5.1 sigma excess in the 2005 data. Above 200 GeV, an integral flux of 0.6+-0.2 x 10^(-11) cm^(-2) s^(-1) was measured, corresponding to approximately 3% of the Crab flux. The differential spectrum between 150 and 900 GeV is rather steep with a photon index of -3.6+-0.5. The light curve shows no significant variability during the observations in 2005. For the first time a clear detection of VHE gamma-ray emission from an LBL object was obtained with a signal below previous upper limits. The 2006 data show no significant excess. This drop in flux follows the observed trend in optical activity., Comment: Accepted for publication in ApJ Letters, 4 pages, 5 figures, Figure-5 revised, Minor corrections following the referee report
Published: 2007

3. Discovery of very high energy gamma-rays from 1ES 1011+496 at z=0.212

Author: J. Albert, E. Aliu, H. Anderhub, P. Antoranz, A. Armada, C. Baixeras, J. A. Barrio, H. Bartko, D. Bastieri, J. K. Becker, W. Bednarek, K. Berger, C. Bigongiari, A. Biland, R. K. Bock, P. Bordas, V. Bosch-Ramon, T. Bretz, I. Britvitch, M. Camara, E. Carmona, A. Chilingarian, J. A. Coarasa, S. Commichau, J. L. Contreras, J. Cortina, M. T. Costado, V. Curtef, V. Danielyan, F. Dazzi, A. De Angelis, C. Delgado, R. de los Reyes, B. De Lotto, E. Domingo-Santamaría, D. Dorner, M. Doro, M. Errando, M. Fagiolini, D. Ferenc, E. Fernández, R. Firpo, J. Flix, M. V. Fonseca, L. Font, M. Fuchs, N. Galante, R. J. García-López, M. Garczarczyk, M. Gaug, M. Giller, F. Goebel, D. Hakobyan, M. Hayashida, T. Hengstebeck, A. Herrero, D. Höhne, J. Hose, C. C. Hsu, P. Jacon, T. Jogler, R. Kosyra, D. Kranich, R. Kritzer, A. Laille, E. Lindfors, S. Lombardi, F. Longo, J. López, M. López, E. Lorenz, P. Majumdar, G. Maneva, K. Mannheim, O. Mansutti, M. Mariotti, M. Martínez, D. Mazin, C. Merck, M. Meucci, M. Meyer, J. M. Miranda, R. Mirzoyan, S. Mizobuchi, A. Moralejo, D. Nieto, K. Nilsson, J. Ninkovic, E. Oña-Wilhelmi, N. Otte, I. Oya, D. Paneque, M. Panniello, R. Paoletti, J. M. Paredes, M. Pasanen, D. Pascoli, F. Pauss, R. Pegna, E. Perlman, M. Persic, L. Peruzzo, A. Piccioli, E. Prandini, N. Puchades, A. Raymers, W. Rhode, M. Ribó, J. Rico, M. Rissi, A. Robert, S. Rügamer, A. Saggion, T. Saito, A. Sánchez, P. Sartori, V. Scalzotto, V. Scapin, R. Schmitt, T. Schweizer, M. Shayduk, K. Shinozaki, S. N. Shore, N. Sidro, A. Sillanpää, D. Sobczynska, A. Stamerra, L. S. Stark, L. Takalo, F. Tavecchio, P. Temnikov, D. Tescaro, M. Teshima, D. F. Torres, N. Turini, H. Vankov, V. Vitale, R. M. Wagner, T. Wibig, W. Wittek, F. Zandanel, R. Zanin, J. Zapatero, J., Albert, E., Aliu, H., Anderhub, P., Antoranz, A., Armada, C., Baixera, J. A., Barrio, H., Bartko, D., Bastieri, J. K., Becker, W., Bednarek, K., Berger, C., Bigongiari, A., Biland, R. K., Bock, P., Borda, V., Bosch Ramon, T., Bretz, I., Britvitch, M., Camara, E., Carmona, A., Chilingarian, J. A., Coarasa, S., Commichau, J. L., Contrera, J., Cortina, M. T., Costado, V., Curtef, V., Danielyan, F., Dazzi, A. D., Angeli, C., Delgado, R. D., Reye, B. D., Lotto, E., Domingo Santamaria, D., Dorner, M., Doro, M., Errando, M., Fagiolini, D., Ferenc, E., Fernandez, R., Firpo, J., Flix, M. V., Fonseca, L., Font, M., Fuch, N., Galante, R. J., Garcia Lopez, M., Garczarczyk, M., Gaug, M., Giller, F., Goebel, D., Hakobyan, M., Hayashida, T., Hengstebeck, A., Herrero, D., Hohne, J., Hose, C. C., Hsu, P., Jacon, T., Jogler, R., Kosyra, D., Kranich, R., Kritzer, A., Laille, E., Lindfor, S., Lombardi, Longo, Francesco, J., Lopez, M., Lopez, E., Lorenz, P., Majumdar, G., Maneva, K., Mannheim, O., Mansutti, M., Mariotti, M., Martinez, D., Mazin, C., Merck, M., Meucci, M., Meyer, J. M., Miranda, R., Mirzoyan, S., Mizobuchi, A., Moralejo, D., Nieto, K., Nilsson, J., Ninkovic, E., Ona Wilhelmi, N., Otte, I., Oya, D., Paneque, M., Panniello, R., Paoletti, J. M., Parede, M., Pasanen, D., Pascoli, F., Pau, R., Pegna, E., Perlman, M., Persic, L., Peruzzo, A., Piccioli, E., Prandini, N., Puchade, A., Raymer, W., Rhode, M., Ribo, J., Rico, M., Rissi, A., Robert, S., Rugamer, A., Saggion, T., Saito, A., Sanchez, P., Sartori, V., Scalzotto, V., Scapin, R., Schmitt, T., Schweizer, M., Shayduk, K., Shinozaki, S. N., Shore, N., Sidro, A., Sillanpaa, D., Sobczynska, A., Stamerra, L. S., Stark, L., Takalo, F., Tavecchio, P., Temnikov, D., Tescaro, M., Teshima, D. F., Torre, N., Turini, H., Vankov, V., Vitale, R. M., Wagner, T., Wibig, W., Wittek, F., Zandanel, R., Zanin, and J., Zapatero
Subjects: Photon, Absorption spectroscopy, Astrophysics::High Energy Astrophysical Phenomena, Flux, FOS: Physical sciences, Astrophysics, Astrophysics::Cosmology and Extragalactic Astrophysics, gamma ray astronomy, Cosmic rays, IMAGING CHERENKOV DETECTOR, quasars: individual (1ES 1011+496), Gamma Rays: Observations, Physics, Astrophysics (astro-ph), Gamma ray, Astronomy and Astrophysics, Active Galactic Nuclei, Redshift, Galaxy, MAGIC telescope, Space and Planetary Science, Very High Energy Gamma-ray Astronomy, Electrónica, Física nuclear, Electricidad, BL Lac object, Visible spectrum
Abstract: We report on the discovery of Very High Energy (VHE) gamma-ray emission from the BL Lacertae object 1ES1011+496. The observation was triggered by an optical outburst in March 2007 and the source was observed with the MAGIC telescope from March to May 2007. Observing for 18.7 hr we find an excess of 6.2 sigma with an integrated flux above 200 GeV of (1.58$\pm0.32) 10^{-11}$ photons cm$^{-2}$ s$^{-1}$. The VHE gamma-ray flux is >40% higher than in March-April 2006 (reported elsewhere), indicating that the VHE emission state may be related to the optical emission state. We have also determined the redshift of 1ES1011+496 based on an optical spectrum that reveals the absorption lines of the host galaxy. The redshift of z=0.212 makes 1ES1011+496 the most distant source observed to emit VHE gamma-rays up to date., 4 pages, 6 figures, minor changes to fit the ApJ version
Published: 2007

4. Upper limit for gamma-ray emission above 140 GeV from the dwarf spheroidal galaxy Draco

Author: J. Albert, E. Aliu, H. Anderhub, P. Antoranz, M. Backes, C. Baixeras, J. A. Barrio, H. Bartko, D. Bastieri, J. K. Becker, W. Bednarek, K. Berger, C. Bigongiari, A. Biland, R. K. Bock, P. Bordas, V. Bosch‐Ramon, T. Bretz, I. Britvitch, M. Camara, E. Carmona, A. Chilingarian, S. Commichau, J. L. Contreras, J. Cortina, M. T. Costado, V. Curtef, V. Danielyan, F. Dazzi, A. De Angelis, C. Delgado, R. de los Reyes, B. De Lotto, M. De Maria, F. De Sabata, D. Dorner, M. Doro, M. Errando, M. Fagiolini, D. Ferenc, E. Fernández, R. Firpo, M. V. Fonseca, L. Font, M. Fuchs, N. Galante, R. J. García‐López, M. Garczarczyk, M. Gaug, F. Goebel, D. Hakobyan, M. Hayashida, T. Hengstebeck, A. Herrero, D. Höhne, J. Hose, S. Huber, C. C. Hsu, P. Jacon, T. Jogler, R. Kosyra, D. Kranich, A. Laille, E. Lindfors, S. Lombardi, F. Longo, M. López, E. Lorenz, P. Majumdar, G. Maneva, N. Mankuzhiyil, K. Mannheim, M. Mariotti, M. Martínez, D. Mazin, C. Merck, M. Meucci, M. Meyer, J. M. Miranda, R. Mirzoyan, S. Mizobuchi, M. Moles, A. Moralejo, D. Nieto, K. Nilsson, J. Ninkovic, E. Oña‐Wilhelmi, N. Otte, I. Oya, M. Panniello, R. Paoletti, J. M. Paredes, M. Pasanen, D. Pascoli, F. Pauss, R. Pegna, M. A. Pérez‐Torres, M. Persic, L. Peruzzo, A. Piccioli, F. Prada, E. Prandini, N. Puchades, A. Raymers, W. Rhode, M. Ribó, J. Rico, M. Rissi, A. Robert, S. Rügamer, A. Saggion, T. Y. Saito, A. Sánchez, M. Sánchez‐Conde, P. Sartori, V. Scalzotto, V. Scapin, R. Schmitt, T. Schweizer, M. Shayduk, K. Shinozaki, S. N. Shore, N. Sidro, A. Sillanpää, D. Sobczynska, F. Spanier, A. Stamerra, L. S. Stark, L. Takalo, P. Temnikov, D. Tescaro, M. Teshima, D. F. Torres, N. Turini, H. Vankov, A. Venturini, V. Vitale, R. M. Wagner, W. Wittek, F. Zandanel, R. Zanin, and J. Zapatero
Subjects: Photon, galaxies: individual: draco, Astrophysics::High Energy Astrophysical Phenomena, Raigs còsmics, Dark matter, Flux, FOS: Physical sciences, Astrophysics, Astrophysics::Cosmology and Extragalactic Astrophysics, Parameter space, dark matter, galaxies: individual (Draco), Cosmic rays, Physics, Cosmology: Dark Matter, galaxies: dwarf, gamma rays: observations, Annihilation, Astrophysics (astro-ph), Gamma ray, Astronomy and Astrophysics, Galaxies, Dwarf spheroidal galaxy, Galàxies, Space and Planetary Science, Dark matter (Astronomy), Neutralino, Electrónica, Física nuclear, dark matter, galaxies: dwarf, galaxies: individual (Draco), gamma rays: observations, Matèria fosca (Astronomia), Electricidad
Abstract: The nearby dwarf spheroidal galaxy Draco with its high mass to light ratio is one of the most auspicious targets for indirect dark matter searches. Annihilation of hypothetical DM particles can result in high-energy gamma-rays, e.g. from neutralino annihilation in the supersymmetric framework. With the MAGIC telescope a search for a possible DM signal originating from Draco was performed during 2007. The analysis of the data results in a flux upper limit of 1.1x10^-11 photons cm^-2 sec^-1 for photon energies above 140 GeV, assuming a point like source. Furthermore, a comparison with predictions from supersymmetric models is given. While our results do not constrain the mSUGRA phase parameter space, a very high flux enhancement can be ruled out., Comment: Accepted for publication by Astrophysical Journal
Published: 2008

5. Correction: Brain mapping across 16 autism mouse models reveals a spectrum of functional connectivity subtypes

Author: V. Zerbi, M. Pagani, M. Markicevic, M. Matteoli, D. Pozzi, M. Fagiolini, Y. Bozzi, A. Galbusera, M. L. Scattoni, G. Provenzano, A. Banerjee, F. Helmchen, M. A. Basson, J. Ellegood, J. P. Lerch, M. Rudin, A. Gozzi, and N. Wenderoth
Subjects: Cellular and Molecular Neuroscience, Psychiatry and Mental health, Molecular Biology
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6. PERIODIC VERY HIGH ENERGY gamma-RAY EMISSION FROM LS I+61 degrees 303 OBSERVED WITH THE MAGIC TELESCOPE

Author: Albert, J., Aliu, E., Anderhub, H., Antonelli, L. A., Antoranz, P., Backes, M., Baixeras, C., Barrio, J. A., Bartko, H., Bastieri, D., Becker, J. K., Bednarek, W., Berger, K., Bernardini, E., Bigongiari, C., Biland, A., Bock, R. K., Bonnoli, G., Bordas, P., Bosch Ramon, V., Bretz, T., Britvitch, I., Camara, M., Carmona, E., Chilingarian, A., Commichau, S., Contreras, J. L., Cortina, J., Costado, M. T., Covino, S., Curtef, V., Dazzi, F., Angelis, A. D., del Pozo, E. D., los Reyes, R. d., Lotto, B. D., Maria, M. D., Sabata, F. D., Mendez, C. D., Dominguez, A., Dorner, D., Doro, M., Errando, M., Fagiolini, M., Ferenc, D., Fernandez, E., Firpo, R., Fonseca, M. V., Font, L., Galante, N., Lopez, R. J. G., Garczarczyk, M., Gaug, M., Goebel, F., Hayashida, M., Herrero, A., Hohne, D., Hose, J., Hsu, C. C., Huber, S., Jogler, T., Kranich, D., Barbera, A. L., Laille, A., Leonardo, E., Lindfors, E., Lombardi, S., Longo, Francesco, Lopez, M., Lorenz, E., Majumdar, P., Maneva, G., Mankuzhiyil, N., Mannheim, K., Maraschi, L., Mariotti, M., Martinez, M., Mazin, D., Meucci, M., Meyer, M., Miranda, J. M., Mirzoyan, R., Mizobuchi, S., Moles, M., Moralejo, A., Nieto, D., Nilsson, K., Ninkovic, J., Otte, N., Oya, I., Panniello, M., Paoletti, R., Paredes, J. M., Pasanen, M., Pascoli, D., Pauss, F., Pegna, R. G., Perez Torres, M. A., Persic, M., Peruzzo, L., Piccioli, A., Prada, F., Prandini, E., Puchades, N., Raymers, A., Rhode, W., Ribo, M., Rico, J., Rissi, M., Robert, A., Rugamer, S., Saggion, A., Saito, T. Y., Salvati, M., Sanchez Conde, M., Sartori, P., Satalecka, K., Scalzotto, V., Scapin, V., Schmitt, R., Schweizer, T., Shayduk, M., Shinozaki, K., Shore, S. N., Sidro, N., Sierpowska Bartosik, A., Sillanpaa, A., Sobczynska, D., Spanier, F., Stamerra, A., Stark, L. S., Takalo, L., Tavecchio, F., Temnikov, P., Tescaro, D., Teshima, M., Tluczykont, M., Torres, D. F., Turini, N., Vankov, H., Venturini, A., Vitale, V., Wagner, R. M., Wittek, W., Zabalza, V., Zandanel, F., Zanin, R., Zapatero, J., J., Albert, E., Aliu, H., Anderhub, L. A., Antonelli, P., Antoranz, M., Backe, C., Baixera, J. A., Barrio, H., Bartko, D., Bastieri, J. K., Becker, W., Bednarek, K., Berger, E., Bernardini, C., Bigongiari, A., Biland, R. K., Bock, G., Bonnoli, P., Borda, V., Bosch Ramon, T., Bretz, I., Britvitch, M., Camara, E., Carmona, A., Chilingarian, S., Commichau, J. L., Contrera, J., Cortina, M. T., Costado, S., Covino, V., Curtef, F., Dazzi, A. D., Angeli, E. D., del Pozo, R. d., los Reye, B. D., Lotto, M. D., Maria, F. D., Sabata, C. D., Mendez, A., Dominguez, D., Dorner, M., Doro, M., Errando, M., Fagiolini, D., Ferenc, E., Fernandez, R., Firpo, M. V., Fonseca, L., Font, N., Galante, R. J. G., Lopez, M., Garczarczyk, M., Gaug, F., Goebel, M., Hayashida, A., Herrero, D., Hohne, J., Hose, C. C., Hsu, S., Huber, T., Jogler, D., Kranich, A. L., Barbera, A., Laille, E., Leonardo, E., Lindfor, S., Lombardi, Longo, Francesco, M., Lopez, E., Lorenz, P., Majumdar, G., Maneva, N., Mankuzhiyil, K., Mannheim, L., Maraschi, M., Mariotti, M., Martinez, D., Mazin, M., Meucci, M., Meyer, J. M., Miranda, R., Mirzoyan, S., Mizobuchi, M., Mole, A., Moralejo, D., Nieto, K., Nilsson, J., Ninkovic, N., Otte, I., Oya, M., Panniello, R., Paoletti, J. M., Parede, M., Pasanen, D., Pascoli, F., Pau, R. G., Pegna, M. A., Perez Torre, M., Persic, L., Peruzzo, A., Piccioli, F., Prada, E., Prandini, N., Puchade, A., Raymer, W., Rhode, M., Ribo, J., Rico, M., Rissi, A., Robert, S., Rugamer, A., Saggion, T. Y., Saito, M., Salvati, M., Sanchez Conde, P., Sartori, K., Satalecka, V., Scalzotto, V., Scapin, R., Schmitt, T., Schweizer, M., Shayduk, K., Shinozaki, S. N., Shore, N., Sidro, A., Sierpowska Bartosik, A., Sillanpaa, D., Sobczynska, F., Spanier, A., Stamerra, L. S., Stark, L., Takalo, F., Tavecchio, P., Temnikov, D., Tescaro, M., Teshima, M., Tluczykont, D. F., Torre, N., Turini, H., Vankov, A., Venturini, V., Vitale, R. M., Wagner, W., Wittek, V., Zabalza, F., Zandanel, R., Zanin, and J., Zapatero
Subjects: Very High Energy Gamma-ray Astronomy, MAGIC telescope, Gamma-ray Binaries, gamma ray astronomy, Cosmic rays, IMAGING CHERENKOV DETECTOR
Abstract: The MAGIC collaboration has recently reported the discovery of gamma-ray emission from the binary system LS I +61 degrees 303 in the TeV energy region. Here we present new observational results on this source in the energy range between 300 GeV and 3 TeV. In total, 112 hr of data were taken between 2006 September and December covering four orbital cycles of this object. This large amount of data allowed us to produce an integral flux light curve covering for the first time all orbital phases of LS I +61 degrees 303. In addition, we also obtained a differential energy spectrum for two orbital phase bins covering the phase range 0.5 < phi < 0.6 and 0.6 < phi < 0.7. The photon index in the two phase bins is consistent within the errors with an average index Gamma = 2.6 +/- 0.2(stat) +/- 0.2(sys). LS I +61 degrees 303 was found to be variable at TeV energies on timescales of days. These new MAGIC measurements allowed us to search for intranight variability of the very high energy emission; however, no evidence for flux variability on timescales down to 30 min was found. To test for possible periodic structures in the light curve, we apply the formalism developed by Lomb and Scargle to the LS I +61 degrees 303 data taken in 2005 and 2006. We found the LS I +61 degrees 303 data set to be periodic with a period of (26.8 +/- 0.2) days (with a post-trial chance probability of 10(-7)), close to the orbital period.
Published: 2009

7. First bounds on the high-energy emission from isolated Wolf-Rayet binary systems

Author: Aliu, E., Anderhub, H., Antonelli, L.A., Antoranz, P., Backes, M., Baixeras, C., Barrio, J.A., Bartko, H., Bastieri, D., K. Becker, J., Bednarek, W., Berger, K., Bernardini, E., Bigongiari, C., Biland, A., K. Bock, R., Bonnoli, G., Bordas, P., Bosch-Ramon, V., Bretz, T., Britvitch, I., Camara, M., Carmona, E., Chilingarian, A., Commichau, S., L. Contreras, J., Cortina, J., T. Costado, M., Covino, S., Curtef, V., Dazzi, F., De Angelis, A., De Ceadel Pozo, E., De Los Reyes, R., De Lotto, B., De Maria, M., De Sabata, F., Delgado Mendez, C., Dominguez, A., Dorner, D., Doro, M., Errando, M., Fagiolini, M., Ferenc, D., Fernández, E., Firpo, R., V. Fonseca, M., Font, L., Galante, N., J. García López, R., Garczarczyk, M., Gaug, M., Goebel, F., Hayashida, M., Herrero, A., Höhne, D., Hose, J., C. Hsu, C., Huber, S., Jogler, T., M. Kneiske, T., Kranich, D., La Barbera, A., Laille, A., Leonardo, E., Lindfors, E., Lombardi, S., Longo, F., López, M., Lorenz, E., Majumdar, P., Maneva, G., Mankuzhiyil, N., Mannheim, K., Maraschi, L., Mariotti, M., Martínez, M., Mazin, D., Meucci, M., Meyer, M., M. Miranda, J., Mirzoyan, R., Mizobuchi, S., Moles, M., Moralejo, A., Nieto, D., Nilsson, K., Ninkovic, J., De Oña Wilhelmi, E., Otte, N., Oya, I., Panniello, M., Paoletti, R., M. Paredes, J., Pasanen, M., Pascoli, D., Pauss, F., G. Pegna, R., A. Perez-Torres, M., Persic, M., Peruzzo, L., Piccioli, A., Prada, F., Prandini, E., Puchades, N., Raymers, A., Rhode, W., Ribó, M., Rico, J., Rissi, M., Robert, A., Rügamer, S., Saggion, A., Y. Saito, T., Salvati, M., Sanchez-Conde, M., Sartori, P., Satalecka, K., Scalzotto, V., Scapin, V., Schmitt, R., Schweizer, T., Shayduk, M., Shinozaki, K., N. Shore, S., Sidro, N., Sierpowska-Bartosik, A., Sillanpää, A., Sobczynska, D., Spanier, F., Stamerra, A., S. Stark, L., Takalo, L., Tavecchio, F., Temnikov, P., Tescaro, D., Teshima, M., Tluczykont, M., F. Torres, D., Turini, N., Vankov, H., Venturini, A., Vitale, V., M. Wagner, R., Wittek, W., Zabalza, V., Zandanel, F., Zanin, R., Zapatero, J., APC - Astrophysique des Hautes Energies (APC - AHE), AstroParticule et Cosmologie (APC (UMR_7164)), Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Dipartimento di Astronomia, Universita degli Studi di Bologna, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO)-Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Universitat de Barcelona, Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Observatoire de Paris, PSL Research University (PSL)-PSL Research University (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Observatoire de Paris, PSL Research University (PSL)-PSL Research University (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Dipartimento di Astronomia, Universita degli Studi di Bologna, Università di Bologna [Bologna] (UNIBO)-Università di Bologna [Bologna] (UNIBO), E., Aliu, H., Anderhub, L. A., Antonelli, P., Antoranz, M., Backe, C., Baixera, J. A., Barrio, H., Bartko, D., Bastieri, J. K., Becker, W., Bednarek, K., Berger, E., Bernardini, C., Bigongiari, A., Biland, R. K., Bock, G., Bonnoli, P., Borda, V., Bosch Ramon, T., Bretz, I., Britvitch, M., Camara, E., Carmona, A., Chilingarian, S., Commichau, J. L., Contrera, J., Cortina, M. T., Costado, S., Covino, V., Curtef, F., Dazzi, A. D., Angeli, E. D., del Pozo, R. D., Reye, B. D., Lotto, M. D., Maria, F. D., Sabata, C. D., Mendez, A., Dominguez, D., Dorner, M., Doro, M., Errando, M., Fagiolini, D., Ferenc, E., Fernandez, R., Firpo, M. V., Fonseca, L., Font, N., Galante, R. J. G., Lopez, M., Garczarczyk, M., Gaug, F., Goebel, M., Hayashida, A., Herrero, D., Hohne, J., Hose, C. C., Hsu, S., Huber, T., Jogler, D., Kranich, A. L., Barbera, A., Laille, E., Leonardo, E., Lindfor, S., Lombardi, Longo, Francesco, M., Lopez, E., Lorenz, P., Majumdar, G., Maneva, N., Mankuzhiyil, K., Mannheim, L., Maraschi, M., Mariotti, M., Martinez, D., Mazin, M., Meucci, M., Meyer, J. M., Miranda, R., Mirzoyan, M., Mole, A., Moralejo, D., Nieto, K., Nilsson, J., Ninkovic, E., Ona Wilhelmi, N., Otte, I., Oya, R., Paoletti, J. M., Parede, M., Pasanen, D., Pascoli, F., Pau, R. G., Pegna, M. A., Perez Torre, M., Persic, L., Peruzzo, A., Piccioli, F., Prada, E., Prandini, N., Puchade, A., Raymer, W., Rhode, M., Ribo, J., Rico, M., Rissi, A., Robert, S., Rugamer, A., Saggion, T. Y., Saito, M., Salvati, M., Sanchez Conde, P., Sartori, K., Satalecka, V., Scalzotto, V., Scapin, T., Schweizer, M., Shayduk, K., Shinozaki, S. N., Shore, N., Sidro, A., Sierpowska Bartosik, A., Sillanpaa, D., Sobczynska, F., Spanier, A., Stamerra, L. S., Stark, L., Takalo, F., Tavecchio, P., Temnikov, D., Tescaro, M., Teshima, M., Tluczykont, D. F., Torre, N., Turini, H., Vankov, A., Venturini, V., Vitale, R. M., Wagner, W., Wittek, V., Zabalza, F., Zandanel, R., Zanin, and J., Zapatero
Subjects: High energy, [SDU.ASTR.CO]Sciences of the Universe [physics]/Astrophysics [astro-ph]/Cosmology and Extra-Galactic Astrophysics [astro-ph.CO], High velocity, Astrophysics::High Energy Astrophysical Phenomena, Binary number, FOS: Physical sciences, Astrophysics, Astrophysics::Cosmology and Extragalactic Astrophysics, Star (graph theory), 01 natural sciences, [PHYS.ASTR.CO]Physics [physics]/Astrophysics [astro-ph]/Cosmology and Extra-Galactic Astrophysics [astro-ph.CO], Wolf–Rayet star, Raigs gamma, Observacions astronòmiques, 0103 physical sciences, Binary star, Astrophysics::Solar and Stellar Astrophysics, WR star binarie, 010303 astronomy & astrophysics, Cosmic rays, Astrophysics::Galaxy Astrophysics, WR star binaries, Physics, Very High Energy Gamma-ray Astronomy, MAGIC telescope, 010308 nuclear & particles physics, gamma ray astronomy, IMAGING CHERENKOV DETECTOR, Astrophysics (astro-ph), Gamma rays, Astronomy and Astrophysics, gamma rays, observations, Space and Planetary Science, High mass, ddc:520, Electrónica, Física nuclear, Electricidad, gamma rays: observations, Astronomical observations
Abstract: High-energy gamma-ray emission is theoretically expected to arise in tight binary star systems (with high mass loss and high velocity winds), although the evidence of this relationship has proven to be elusive so far. Here we present the first bounds on this putative emission from isolated Wolf-Rayet (WR) star binaries, WR 147 and WR 146, obtained from observations with the MAGIC telescope., (Authors are the MAGIC Collaboration.) Manuscript in press at The Astrophysical Journal Letters
Published: 2008
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8. Observation of pulsed gamma-rays above 25 GeV from the Crab pulsar with MAGIC

Author: A. Saggion, Adrian Biland, Manel Errando, Giacomo Bonnoli, Mariano Moles, P. Temnikov, Fabio Zandanel, J. Rico, K. Berger, V. Curtef, L. O. Takalo, J. K. Becker, M. Shayduk, Aaron Dominguez, Mosè Mariotti, A. Herrero, Felicitas Pauss, Konstancja Satalecka, J. A. Barrio, Miriam Lucio Martinez, P. Bordas, Michele Doro, Alessio Venturini, L. S. Stark, Kari Nilsson, Igor Oya, Fabrizio Tavecchio, Jelena Ninkovic, Saverio Lombardi, H. Anderhub, Daniel Kranich, Victor Zabalza, Abelardo Moralejo, J. M. Paredes, Daniel Ferenc, Michael Backes, R. K. Bock, Francesco Dazzi, Antonio Stamerra, Masahiro Teshima, D. Pascoli, Miguel A. Sánchez-Conde, C. Delgado Mendez, H. Vankov, I. Britvitch, E. Leonardo, R. Paoletti, T. Schweizer, Felix Spanier, Denis Bastieri, C. Baixeras, A. Robert, H. Bartko, Dominik Elsässer, A. Raymers, E. Fernandez, A. Sillanpää, Robert Wagner, R. Firpo, M. S. Meyer, Daniela Dorner, Takashi Saito, L. A. Antonelli, A. Laille, V. Scalzotto, M. Salvati, D. Mazin, A. Piccioli, Nicola Galante, J. Hose, M. Gaug, W. Wittek, Daniela Hadasch, P. Sartori, O. C. de Jager, N. Mankuzhiyil, Karl Mannheim, E. Lorenz, Florian Goebel, M. Tluczykont, Elisa Bernardini, R. de los Reyes, Nicola Turini, V. Scapin, Valentí Bosch-Ramon, Francisco Prada, S. Commichau, Jose Luis Contreras, Wlodek Bednarek, Daniel Nieto, C. C. Hsu, Juan Cortina, T. Jogler, D. Höhne, P. Antoranz, Mario Meucci, M. De Maria, Jose Miguel Miranda, L. Peruzzo, M. A. Lopez, Diego F. Torres, Ciro Bigongiari, A. La Barbera, M. Pasanen, M. Garczarczyk, N. Sidro, B. De Lotto, A. De Angelis, Dorota Sobczyńska, E. Prandini, G. Maneva, K. Shinozaki, E. de Oña Wilhelmi, Roberta Zanin, E. De Cea del Pozo, V. Vitale, R. Mirzoyan, Lluis Font, E. Carmona, Thomas Bretz, Wolfgang Rhode, Michela Fagiolini, Stefano Covino, Ashot Chilingarian, N. Puchades, N. Otte, R. J. García López, Agnieszka Sierpowska-Bartosik, J. Zapatero, M. Camara, F. De Sabata, D. Tescaro, Massimo Persic, L. Maraschi, E. Aliu, Elina Lindfors, F. Longo, R. G. Pegna, Pratik Majumdar, M. V. Fonseca, M. Rissi, M. Hayashida, S. N. Shore, Marc Ribó, M. T. Costado, Miguel A. Pérez-Torres, S. Rügamer, S. Huber, E., Aliu, H., Anderhub, L. A., Antonelli, P., Antoranz, M., Backe, C., Baixera, J. A., Barrio, H., Bartko, D., Bastieri, J. K., Becker, W., Bednarek, K., Berger, E., Bernardini, C., Bigongiari, A., Biland, R. K., Bock, G., Bonnoli, P., Borda, V., Bosch Ramon, T., Bretz, I., Britvitch, M., Camara, E., Carmona, A., Chilingarian, S., Commichau, J. L., Contrera, J., Cortina, M. T., Costado, S., Covino, V., Curtef, F., Dazzi, A. D., Angeli, E. D. C., del Pozo, R. d., los Reye, B. D., Lotto, M. D., Maria, F. D., Sabata, C. D., Mendez, A., Dominguez, D., Dorner, M., Doro, D., Elsasser, M., Errando, M., Fagiolini, D., Ferenc, E., Fernandez, R., Firpo, M. V., Fonseca, L., Font, N., Galante, R. J. G., Lopez, M., Garczarczyk, M., Gaug, F., Goebel, D., Hadasch, M., Hayashida, A., Herrero, D., Hohne, J., Hose, C. C., Hsu, S., Huber, T., Jogler, D., Kranich, A. L., Barbera, A., Laille, E., Leonardo, E., Lindfor, S., Lombardi, Longo, Francesco, M., Lopez, E., Lorenz, P., Majumdar, G., Maneva, N., Mankuzhiyil, K., Mannheim, L., Maraschi, M., Mariotti, M., Martinez, D., Mazin, M., Meucci, M., Meyer, J. M., Miranda, R., Mirzoyan, M., Mole, A., Moralejo, D., Nieto, K., Nilsson, J., Ninkovic, N., Otte, I., Oya, R., Paoletti, J. M., Parede, M., Pasanen, D., Pascoli, F., Pau, R. G., Pegna, M. A., Perez Torre, M., Persic, L., Peruzzo, A., Piccioli, F., Prada, E., Prandini, N., Puchade, A., Raymer, W., Rhode, M., Ribo, J., Rico, M., Rissi, A., Robert, S., Rugamer, A., Saggion, T. Y., Saito, M., Salvati, M., Sanchez Conde, P., Sartori, K., Satalecka, V., Scalzotto, V., Scapin, T., Schweizer, M., Shayduk, K., Shinozaki, S. N., Shore, N., Sidro, A., Sierpowska Bartosik, A., Sillanpaa, D., Sobczynska, F., Spanier, A., Stamerra, L. S., Stark, L., Takalo, F., Tavecchio, P., Temnikov, D., Tescaro, M., Teshima, M., Tluczykont, D. F., Torre, N., Turini, H., Vankov, A., Venturini, V., Vitale, R. M., Wagner, W., Wittek, V., Zabalza, F., Zandanel, R., Zanin, J., Zapatero, O. C., de Jager, E. D., Wilhelmi, and Universitat de Barcelona
Subjects: Astrophysics::High Energy Astrophysical Phenomena, Phase (waves), FOS: Physical sciences, Magnetosphere, Astrophysics, Electromagnetisme, Space telescopes, 01 natural sciences, law.invention, Magnetosfera, Telescope, Electromagnetism, Pulsar, Very High Energy Gamma-ray Astronomy, MAGIC telescope, law, Gamma ray astronomy, 0103 physical sciences, Astronomia de raigs gamma, Cutoff, MAGIC (telescope), VHE gamma rays from Crab, 010303 astronomy & astrophysics, Pulsars, Cherenkov radiation, Physics, Multidisciplinary, gamma-ray Imaging Cherenkov telescopes, Synchrotron radiation, 010308 nuclear & particles physics, Crab Pulsar, Astrophysics (astro-ph), Astrophysics::Instrumentation and Methods for Astrophysics, Radiació sincrotrònica, MAGIC, Púlsars, Electrónica, Física nuclear, Electricidad, Telescopis espacials
Abstract: One fundamental question about pulsars concerns the mechanism of their pulsed electromagnetic emission. Measuring the high-end region of a pulsar's spectrum would shed light on this question. By developing a new electronic trigger, we lowered the threshold of the Major Atmospheric gamma-ray Imaging Cherenkov (MAGIC) telescope to 25 GeV. In this configuration, we detected pulsed gamma-rays from the Crab pulsar that were greater than 25 GeV, revealing a relatively high cutoff energy in the phase-averaged spectrum. This indicates that the emission occurs far out in the magnetosphere, hence excluding the polar-cap scenario as a possible explanation of our measurement. The high cutoff energy also challenges the slot-gap scenario., Comment: Slight modification of the analysis: Fitting a more general function to the combined data set of COMPTEL, EGRET and MAGIC. Final result and conclusion is unchanged
Published: 2008
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9. First bounds on the very high energy γ-ray emission from Arp 220

Author: Albert, J., Aliu, E., Anderhub, H., Antoranz, P., Armada, A., Baixeras, C., Barrio, J. A., Bartko, H., Bastieri, D., Becker, J., Bednarek, W., Berger, K., Bigongiari, C., Biland, A., Bock, R. K., Bordas, P., Bosch Ramon, V., Bretz, T., Britvitch, I., Camara, M., Carmona, E., Chilingarian, A., Ciprini, S., Coarasa, J. A., Commichau, S., Contreras, J. L., Cortina, J., Curtef, V., Danielyan, V., Dazzi, F., Angelis, A. D., Los, R. D., Lotto, B. D., Domingo Santamaria, E., Dorner, D., Doro, M., Errando, M., Fagiolini, M., Ferenc, D., Fernandez, E., Firpo, R., Flix, J., Fonseca, M. V., Font, L., Fuchs, M., Galante, N., Garczarczyk, M., Gaug, M., Giller, M., Goebel, F., Hakobyan, D., Hayashida, M., Hengstebeck, T., Hohne, D., Hose, J., Hsu, C. C., Jacon, P., Jogler, T., Kalekin, O., Kosyra, R., Kranich, D., Kritzer, R., Laille, A., Liebing, P., Lindfors, E., Lombardi, S., Longo, F., Lopez, J., Lopez, M., Lorenz, E., Majumdar, P., Maneva, G., Mannheim, K., Mansutti, O., Mariotti, M., Martinez, M., Mazin, D., Merck, C., Meucci, M., Meyer, M., Miranda, J. M., Mirzoyan, R., Mizobuchi, S., Moralejo, A., Nilsson, K., Ninkovic, J., Ona Wilhelmi, E., Otte, N., Oya, I., Paneque, D., Paoletti, Riccardo, Paredes, J. M., Pasanen, M., Pascoli, D., Pauss, F., Pegna, R., Persic, M., Peruzzo, L., Piccioli, A., Poller, M., Puchades, N., Prandini, E., Raymers, A., Rhode, W., Ribo, M., Rico, J., Rissi, M., Robert, A., Rugamer, S., Saggion, A., Sanchez, A., Sartori, P., Scalzotto, V., Scapin, V., Schmitt, R., Schweizer, T., Shayduk, M., Shinozaki, K., Shore, S. N., Sidro, N., Sillanpaa, A., Sobczynska, D., Stamerra, Antonio, Stark, L. S., Takalo, L., Temnikov, P., Tescaro, D., Teshima, M., Tonello, N., Torres, D. F., Turini, N., Vankov, H., Vitale, V., Wagner, R. M., Wibig, T., Wittek, W., Zanin, R., Zapatero, J., J., Albert, E., Aliu, H., Anderhub, P., Antoranz, A., Armada, C., Baixera, J. A., Barrio, H., Bartko, D., Bastieri, J., Becker, W., Bednarek, K., Berger, C., Bigongiari, A., Biland, R. K., Bock, P., Borda, V., Bosch Ramon, T., Bretz, I., Britvitch, M., Camara, E., Carmona, A., Chilingarian, S., Ciprini, J. A., Coarasa, S., Commichau, J. L., Contrera, J., Cortina, V., Curtef, V., Danielyan, F., Dazzi, A. D., Angeli, R. D., Los Reye, B. D., Lotto, E., Domingo Santamaria, D., Dorner, M., Doro, M., Errando, M., Fagiolini, D., Ferenc, E., Fernandez, R., Firpo, J., Flix, M. V., Fonseca, L., Font, M., Fuch, N., Galante, M., Garczarczyk, M., Gaug, M., Giller, F., Goebel, D., Hakobyan, M., Hayashida, T., Hengstebeck, D., Hohne, J., Hose, C. C., Hsu, P., Jacon, T., Jogler, O., Kalekin, R., Kosyra, D., Kranich, R., Kritzer, A., Laille, P., Liebing, E., Lindfor, S., Lombardi, Longo, Francesco, J., Lopez, M., Lopez, E., Lorenz, P., Majumdar, G., Maneva, K., Mannheim, O., Mansutti, M., Mariotti, M., Martinez, D., Mazin, C., Merck, M., Meucci, M., Meyer, J. M., Miranda, R., Mirzoyan, S., Mizobuchi, A., Moralejo, K., Nilsson, J., Ninkovic, E., Ona Wilhelmi, N., Otte, I., Oya, D., Paneque, R., Paoletti, J. M., Parede, M., Pasanen, D., Pascoli, F., Pau, R., Pegna, M., Persic, L., Peruzzo, A., Piccioli, M., Poller, N., Puchade, E., Prandini, A., Raymer, W., Rhode, M., Ribo, J., Rico, M., Rissi, A., Robert, S., Rugamer, A., Saggion, A., Sanchez, P., Sartori, V., Scalzotto, V., Scapin, R., Schmitt, T., Schweizer, M., Shayduk, K., Shinozaki, S. N., Shore, N., Sidro, A., Sillanpaa, D., Sobczynska, A., Stamerra, L. S., Stark, L., Takalo, P., Temnikov, D., Tescaro, M., Teshima, N., Tonello, D. F., Torre, N., Turini, H., Vankov, V., Vitale, R. M., Wagner, T., Wibig, W., Wittek, R., Zanin, J., Zapatero, and Universitat de Barcelona
Subjects: ULTRALUMINOUS INFRARED GALAXIES, High energy, Infrared, IMAGES, Astrophysics::High Energy Astrophysical Phenomena, FOS: Physical sciences, Flux, Astrophysics, Astrophysics::Cosmology and Extragalactic Astrophysics, gamma ray astronomy, Cosmic rays, IMAGING CHERENKOV DETECTOR, Galaxie, STAR-FORMATION, law.invention, Telescope, Raigs gamma, law, HESS, MAGIC (telescope), Cherenkov radiation, Astrophysics::Galaxy Astrophysics, Physics, Astrophysics (astro-ph), Gamma rays, Gamma ray, MAGIC TELESCOPE, REGIONS, EGRET, Astronomy and Astrophysics, Galaxies, Galaxy, MAGIC telescope, Space and Planetary Science, Very High Energy Gamma-ray Astronomy, Electrónica, Física nuclear, Electricidad
Abstract: Using the Major Atmospheric Gamma Imaging Cherenkov Telescope (MAGIC), we have observed the nearest ultra-luminous infrared galaxy Arp 220 for about 15 hours. No significant signal was detected within the dedicated amount of observation time. The first upper limits to the very high energy $\gamma$-ray flux of Arp 220 are herein reported and compared with theoretical expectations., Comment: Accepted for publication in ApJ
Published: 2007

10. Observation of very high energy gamma-rays from the AGN 1ES 2344+514 in low emission state with the magic telescope

Author: Albert, J., Aliu, E., Anderhub, H., Antoranz, P., Armada, A., Baixeras, C., Barrio, J. A., Bartko, H., Bastieri, D., Becker, J. K., Bednarek, W., Berger, K., Bigongiari, C., Biland, A., Bock, R. K., Bordas, P., Bosch Ramon, V., Bretz, T., Britvitch, I., Camara, M., Carmona, E., Chilingarian, A., Ciprini, S., Coarasa, J. A., Commichau, S., Contreras, J. L., Cortina, J., Costado, M. T., Curtef, V., Danielyan, V., Dazzi, F., Angelis, A. D., Delgado, C., Reyes, R. D. L., Lotto, B. D., Domingo Santamaria, E., Dorner, D., Doro, M., Errando, M., Fagiolini, M., Angelis, D., Ferenc, D., Fernandez, E., Firpo, R., Flix, J., Fonseca, M. V., Font, L., Fuchs, M., Galante, N., Garcia Lopez, R., Garczarczyk, M., Gaug, M., Giller, M., Goebel, F., Hakobyan, D., Hayashida, M., Hengstebeck, T., Herrero, A., Hohne, D., Hose, J., Hsu, C. C., Jacon, P., Jogler, T., Kalekin, O., Kosyra, R., Kranich, D., Kritzer, R., Laille, A., Liebing, P., Lindfors, E., Lombardi, S., Longo, Francesco, Lopez, J., Lopez, M., Lorenz, E., Majumdar, P., Maneva, G., Mannheim, K., Mansutti, O., Mariotti, M., Martinez, M., Mazin, D., Merck, C., Meucci, M., Meyer, M., Miranda, J. M., Mirzoyan, R., Mizobuchi, S., Moralejo, A., Nilsson, K., Ninkovic, J., Onna Wilhelmi, E., Otte, N., Oya, I., Paneque, D., Panniello, M., Paoletti, R., Paredes, J. M., Pasanen, M., Pascoli, D., Pauss, F., Pegna, R., Persic, M., Peruzzo, L., Piccioli, A., Poller, M., Prandini, E., Puchades, N., Raymers, A., Rhode, W., Ribo, M., Rico, J., Rissi, M., Robert, A., Rugamer, S., Saggion, A., Sanchez, A., Sartori, P., Scalzotto, V., Scapin, V., Schmitt, R., Schweizer, T., Shayduk, M., Shinozaki, K., Shore, S. N., Sidro, N., Sillanpaa, A., Sobczynska, D., Stamerra, A., Stark, L. S., Takalo, L., Temnikov, P., Tescaro, D., Teshima, M., Tonello, N., Torres, D. F., Turini, N., Vankov, H., Vitale, V., Wagner, R. M., Wibig, T., Wittek, W., Zandanel, F., Zanin, R., Zapatero, J., J., Albert, E., Aliu, H., Anderhub, P., Antoranz, A., Armada, C., Baixera, J. A., Barrio, H., Bartko, D., Bastieri, J. K., Becker, W., Bednarek, K., Berger, C., Bigongiari, A., Biland, R. K., Bock, P., Borda, V., Bosch Ramon, T., Bretz, I., Britvitch, M., Camara, E., Carmona, A., Chilingarian, S., Ciprini, J. A., Coarasa, S., Commichau, J. L., Contrera, J., Cortina, M. T., Costado, V., Curtef, V., Danielyan, F., Dazzi, A. D., Angeli, C., Delgado, R. D. L., Reye, B. D., Lotto, E., Domingo Santamaria, D., Dorner, M., Doro, M., Errando, M., Fagiolini, D., Angeli, D., Ferenc, E., Fernandez, R., Firpo, J., Flix, M. V., Fonseca, L., Font, M., Fuch, N., Galante, R., Garcia Lopez, M., Garczarczyk, M., Gaug, M., Giller, F., Goebel, D., Hakobyan, M., Hayashida, T., Hengstebeck, A., Herrero, D., Hohne, J., Hose, C. C., Hsu, P., Jacon, T., Jogler, O., Kalekin, R., Kosyra, D., Kranich, R., Kritzer, A., Laille, P., Liebing, E., Lindfor, S., Lombardi, Longo, Francesco, J., Lopez, M., Lopez, E., Lorenz, P., Majumdar, G., Maneva, K., Mannheim, O., Mansutti, M., Mariotti, M., Martinez, D., Mazin, C., Merck, M., Meucci, M., Meyer, J. M., Miranda, R., Mirzoyan, S., Mizobuchi, A., Moralejo, K., Nilsson, J., Ninkovic, E., Onna Wilhelmi, N., Otte, I., Oya, D., Paneque, M., Panniello, R., Paoletti, J. M., Parede, M., Pasanen, D., Pascoli, F., Pau, R., Pegna, M., Persic, L., Peruzzo, A., Piccioli, M., Poller, E., Prandini, N., Puchade, A., Raymer, W., Rhode, M., Ribo, J., Rico, M., Rissi, A., Robert, S., Rugamer, A., Saggion, A., Sanchez, P., Sartori, V., Scalzotto, V., Scapin, R., Schmitt, T., Schweizer, M., Shayduk, K., Shinozaki, S. N., Shore, N., Sidro, A., Sillanpaa, D., Sobczynska, A., Stamerra, L. S., Stark, L., Takalo, P., Temnikov, D., Tescaro, M., Teshima, N., Tonello, D. F., Torre, N., Turini, H., Vankov, V., Vitale, R. M., Wagner, T., Wibig, W., Wittek, F., Zandanel, R., Zanin, and J., Zapatero
Subjects: ACTIVE GALACTIC NUCLEI, High energy, Photon, Astrophysics::High Energy Astrophysical Phenomena, UNIVERSE, Flux, FOS: Physical sciences, Astrophysics, gamma ray astronomy, Cosmic rays, IMAGING CHERENKOV DETECTOR, 01 natural sciences, Power law, law.invention, law, 0103 physical sciences, SPECTRA, MAGIC (telescope), 010303 astronomy & astrophysics, MULTIWAVELENGTH OBSERVATIONS, Physics, 010308 nuclear & particles physics, CHERENKOV TELESCOPES, Astrophysics (astro-ph), Gamma ray, HEGRA, EINSTEIN SLEW SURVEY, Astronomy and Astrophysics, Active Galactic Nuclei, BL-LACERTAE OBJECTS, MAGIC telescope, LAC OBJECTS, DISCOVERY, RADIATION, Space and Planetary Science, Very High Energy Gamma-ray Astronomy, Electrónica, Física nuclear, High Energy Physics::Experiment, Electricidad, Flare
Abstract: The MAGIC collaboration has observed very high energy gamma ray emission from the AGN 1ES 2344+514. A gamma-ray signal corresponding to an 11 sigma excess and an integral flux of (2.38+-0.30(stat)+-0.70(syst))*10^-11 cm^-2 s^-1 above 200 GeV has been obtained from 23.1 hours of data taking between 2005 August 3 and 2006 January 1. The data confirm the previously detected gamma-ray emission from this object during a flare seen by the Whipple collaboration in 1995 and the evidence (below 5 sigma significance level) from long-term observations conducted by the Whipple and HEGRA groups. The MAGIC observations show a relatively steep differential photon spectrum that can be described by a power law with a photon index of alpha=-2.95+-0.12(stat)+-0.2(syst) between 140 GeV and 5.4 TeV. The observations reveal a low flux state, about six times below the 1995 flare seen by Whipple and comparable with the previous Whipple and HEGRA long term measurements. During the MAGIC observations no significant time variability has been observed., Comment: 7 pages, 7 figures, ApJ in press; updated fig. 4, fig. 7, tab. 3, removed typo in differential spectra
Published: 2007

11. Observation of VHE gamma-rays from Cassiopeia A with the MAGIC telescope

Author: Valentí Bosch-Ramon, Maria Giller, V. Scapin, M. Camara, V. Vitale, Abelardo Moralejo, Jorge Andres Lopez Lopez, E. Carmona, A. Sillanpää, H. Anderhub, T. Schweizer, V. Scalzotto, P. Jacon, P. Sartori, Daniela Dorner, Francesco Longo, W. Wittek, Mosè Mariotti, P. Antoranz, A. Saggion, Masahiro Teshima, Adrian Biland, M. Poller, J. Hose, C. Baixeras, Jelena Ninkovic, Petar Temnikov, M. López, Markus Gaug, Elisa Prandini, Florian Goebel, Riccardo Paoletti, W. Bednarek, Manel Errando, Jose Flix, F. Pauss, Saverio Lombardi, Julia Becker, Ll. Font, A. Robert, S. Commichau, A. Armada, R. Kritzer, Francesco Dazzi, Juan Abel Barrio, Ashot Chilingarian, V. Danielyan, B. De Lotto, V. Curtef, L. S. Stark, Masaaki Hayashida, E. Oña-Wilhelmi, Jose Luis Contreras, J. M. Paredes, Antonio Stamerra, D. Tescaro, I. Britvitch, H. Bartko, Jose Miguel Miranda, Juan Cortina, Tadeusz Wibig, J. A. Coarasa, L. O. Takalo, E. Lorenz, N. Puchades, E. Fernandez, R. Pegna, Pol Bordas, Michele Doro, K. Nilsson, R. Firpo, F. Zandanel, N. Tonello, J. Rico, Thomas Bretz, S. N. Shore, Diego F. Torres, Ciro Bigongiari, R. Mirzoyan, A. Laille, M. Shayduk, N. Otte, M. Pasanen, A. Raymers, A. De Angelis, L. Peruzzo, R. de los Reyes, Nicola Turini, C. Delgado, A. Piccioli, K. Berger, David Paneque, M. Panniello, M. I. Martínez, Nicola Galante, G. Maneva, N. Sidro, Wolfgang Rhode, D. Pascoli, M. Fuchs, Massimo Persic, R. Kosyra, Robert Wagner, K. Mannheim, M. Meyer, C. C. Hsu, M. Garczarczyk, C. Merck, E. Aliu, R. Schmitt, Elina Lindfors, Daniel Mazin, S. Rügamer, Michela Fagiolini, Oriana Mansutti, Dorota Sobczyńska, Justin Albert, J. Zapatero, I. Oya, K. Shinozaki, Roberta Zanin, E. Domingo-Santamaría, A. Herrero, T. Jogler, D. Höhne, R. J. García-López, R. K. Bock, M. Rissi, D. Kranich, T. Hengstebeck, Denis Bastieri, D. Hakobyan, S. Mizobuchi, Alvaro Sanchez, Marc Ribó, M. T. Costado, Daniel Ferenc, H. Vankov, P. Majumdar, Mario Meucci, M. V. Fonseca, Universitat de Barcelona, J., Albert, E., Aliu, H., Anderhub, P., Antoranz, A., Armada, C., Baixera, J. A., Barrio, H., Bartko, D., Bastieri, J. K., Becker, W., Bednarek, K., Berger, C., Bigongiari, A., Biland, R. K., Bock, P., Borda, V., Bosch Ramon, T., Bretz, I., Britvitch, M., Camara, E., Carmona, A., Chilingarian, J. A., Coarasa, S., Commichau, J. L., Contrera, J., Cortina, M. T., Costado, V., Curtef, V., Danielyan, F., Dazzi, A. D., Angeli, C., Delgado, R. d., los Reye, B. D., Lotto, E., Domingo Santamaria, D., Dorner, M., Doro, M., Errando, M., Fagiolini, D., Ferenc, E., Fernandez, R., Firpo, J., Flix, M. V., Fonseca, L., Font, M., Fuch, N., Galante, R., Garcia Lopez, M., Garczarczyk, M., Gaug, M., Giller, F., Goebel, D., Hakobyan, M., Hayashida, T., Hengstebeck, A., Herrero, D., Hohne, J., Hose, C. C., Hsu, P., Jacon, T., Jogler, R., Kosyra, D., Kranich, R., Kritzer, A., Laille, E., Lindfor, S., Lombardi, Longo, Francesco, J., Lopez, M., Lopez, E., Lorenz, P., Majumdar, G., Maneva, K., Mannheim, O., Mansutti, M., Mariotti, M., Martinez, D., Mazin, C., Merck, M., Meucci, M., Meyer, J. M., Miranda, R., Mirzoyan, S., Mizobuchi, A., Moralejo, K., Nilsson, J., Ninkovic, E., Ona Wilhelmi, N., Otte, I., Oya, D., Paneque, M., Panniello, R., Paoletti, J. M., Parede, M., Pasanen, D., Pascoli, F., Pau, R., Pegna, M., Persic, L., Peruzzo, A., Piccioli, M., Poller, N., Puchade, E., Prandini, A., Raymer, W., Rhode, M., Ribo, J., Rico, M., Rissi, A., Robert, S., Rugamer, A., Saggion, A., Sanchez, P., Sartori, V., Scalzotto, V., Scapin, R., Schmitt, T., Schweizer, M., Shayduk, K., Shinozaki, S. N., Shore, N., Sidro, A., Sillanpaa, D., Sobczynska, A., Stamerra, L. S., Stark, L., Takalo, P., Temnikov, D., Tescaro, M., Teshima, N., Tonello, D. F., Torre, N., Turini, H., Vankov, V., Vitale, R. M., Wagner, T., Wibig, W., Wittek, F., Zandanel, R., Zanin, and J., Zapatero
Subjects: Astrofísica, Photon, Raigs còsmics, Astronomy, PROGENITOR, Astrophysics, law.invention, Raigs gamma, law, Supernova remnant, Physics, SUPERNOVA-REMNANTS, Supernoves, Astrophysics (astro-ph), Gamma ray, 5 GHZ, Particle acceleration, Supernovae, Electrónica, Física nuclear, Electricidad, Very High Energy Gamma-ray Astronomy, Supernova remnants, MAGIC telescope, Telescopis espacials, Astrophysics::High Energy Astrophysical Phenomena, FOS: Physical sciences, Cosmic ray, Astrophysics::Cosmology and Extragalactic Astrophysics, ACCELERATION, gamma ray astronomy, Cosmic rays, IMAGING CHERENKOV DETECTOR, Space telescopes, Telescope, Angular resolution, Astrophysics::Galaxy Astrophysics, Gamma rays, Astronomy and Astrophysics, Cassiopeia A, Space and Planetary Science, EMISSION, Astronomia, High Energy Physics::Experiment
Abstract: We searched for very high energy (VHE) gamma-ray emission from the supernova remnant Cassiopeia A. The shell-type supernova remnant Cassiopeia A was observed with the 17 meter MAGIC telescope between July 2006 and January 2007 for a total time of 47 hours. The source was detected above an energy of 250 GeV with a significance of 5.2sigma and a photon flux above 1 TeV of (7.3+-0.7_stat+-2.2_sys)10^-13 cm^-2s^-1. The photon spectrum is compatible with a power law dN/dE = A E^-Gamma with a photon index Gamma=2.3+-0.2_stat+-0.2_sys. The source is point-like within the angular resolution of the telescope., Comment: 4 pages, 4 figures, submitted to A&A
Published: 2007

12. Discovery of very high energy gamma radiation from IC 443 with the MAGIC telescope

Author: Daniela Dorner, K. Berger, Manel Errando, H. Anderhub, M. Shayduk, J. Hose, A. Raymers, A. De Angelis, Petar Temnikov, M. Camara, A. Piccioli, Nicola Galante, M. I. Martínez, T. Hengstebeck, P. Jacon, V. Danielyan, Florian Goebel, Dorota Sobczyńska, I. Britvitch, Justin Albert, M. Rissi, C. Merck, J. M. Paredes, P. Sartori, Denis Bastieri, N. Puchades, Antonio Stamerra, Elina Lindfors, N. Otte, D. Kranich, V. Curtef, A. Sillanpää, Takashi Saito, M. López, Alvaro Sanchez, Daniel Mazin, A. Armada, Masahiro Teshima, E. Oña-Wilhelmi, R. J. García-López, D. Pascoli, S. Rügamer, D. Hakobyan, S. Mizobuchi, Thomas Bretz, A. Saggion, S. N. Shore, Elisa Prandini, Enrique Fernández, M. Fuchs, Massimo Persic, L. O. Takalo, R. Firpo, R. Schmitt, Marc Ribó, Juan Abel Barrio, Valentí Bosch-Ramon, R. Mirzoyan, Adrian Biland, Michele Doro, V. Scapin, Daniel Nieto, Markus Gaug, J. A. Coarasa, M. T. Costado, V. Vitale, Michela Fagiolini, Oriana Mansutti, Artemio Herrero, A. Robert, Mario Meucci, M. Panniello, Ashot Chilingarian, T. Jogler, E. Aliu, D. Höhne, C. Delgado, Francesco Longo, Wolfgang Rhode, K. Shinozaki, R. K. Bock, F. Pauss, T. Schweizer, R. Kosyra, Robert Wagner, M. V. Fonseca, F. Zandanel, L. S. Stark, J. Zapatero, Riccardo Paoletti, I. Oya, W. Wittek, P. Antoranz, Roberta Zanin, Daniel Ferenc, J. Rico, A. Laille, Mosè Mariotti, H. Vankov, N. Sidro, Julia Becker, S. Commichau, K. Nilsson, M. Pasanen, David Paneque, E. Domingo-Santamaría, P. Majumdar, C. C. Hsu, K. Mannheim, R. de los Reyes, Nicola Turini, M. Meyer, M. Garczarczyk, Jose Miguel Miranda, L. Peruzzo, Saverio Lombardi, Maria Giller, E. Carmona, G. Maneva, C. Baixeras, Pol Bordas, D. Tescaro, Tadeusz Wibig, E. Lorenz, V. Scalzotto, Masaaki Hayashida, Jose Luis Contreras, Juan Cortina, R. Pegna, W. Bednarek, Jose Flix, Ll. Font, Jelena Ninkovic, Francesco Dazzi, Diego F. Torres, Ciro Bigongiari, J. López, R. Kritzer, B. De Lotto, H. Bartko, Abelardo Moralejo, J., Albert, E., Aliu, H., Anderhub, P., Antoranz, A., Armada, C., Baixera, J. A., Barrio, H., Bartko, D., Bastieri, J. K., Becker, W., Bednarek, K., Berger, C., Bigongiari, A., Biland, R. K., Bock, P., Borda, V., Bosch Ramon, T., Bretz, I., Britvitch, M., Camara, E., Carmona, A., Chilingarian, J. A., Coarasa, S., Commichau, J. L., Contrera, J., Cortina, M. T., Costado, V., Curtef, V., Danielyan, F., Dazzi, A. D., Angeli, C., Delgado, R. d., los Reye, B. D., Lotto, E., Domingo Santamaria, D., Dorner, M., Doro, M., Errando, M., Fagiolini, D., Ferenc, E., Fernandez, R., Firpo, J., Flix, M. V., Fonseca, L., Font, M., Fuch, N., Galante, R. J., Garcia Lopez, M., Garczarczyk, M., Gaug, M., Giller, F., Goebel, D., Hakobyan, M., Hayashida, T., Hengstebeck, A., Herrero, D., Hohne, J., Hose, C. C., Hsu, P., Jacon, T., Jogler, R., Kosyra, D., Kranich, R., Kritzer, A., Laille, E., Lindfor, S., Lombardi, Longo, Francesco, J., Lopez, M., Lopez, E., Lorenz, P., Majumdar, G., Maneva, K., Mannheim, O., Mansutti, M., Mariotti, M., Martinez, D., Mazin, C., Merck, M., Meucci, M., Meyer, J. M., Miranda, R., Mirzoyan, S., Mizobuchi, A., Moralejo, D., Nieto, K., Nilsson, J., Ninkovic, E., Ona Wilhelmi, N., Otte, I., Oya, D., Paneque, M., Panniello, R., Paoletti, J. M., Parede, M., Pasanen, D., Pascoli, F., Pau, R., Pegna, M., Persic, L., Peruzzo, A., Piccioli, E., Prandini, N., Puchade, A., Raymer, W., Rhode, M., Ribo, J., Rico, M., Rissi, A., Robert, S., Rugamer, A., Saggion, T., Saito, A., Sanchez, P., Sartori, V., Scalzotto, V., Scapin, R., Schmitt, T., Schweizer, M., Shayduk, K., Shinozaki, S. N., Shore, N., Sidro, A., Sillanpaa, D., Sobczynska, A., Stamerra, L. S., Stark, L., Takalo, P., Temnikov, D., Tescaro, M., Teshima, D. F., Torre, N., Turini, H., Vankov, V., Vitale, R. M., Wagner, T., Wibig, W., Wittek, F., Zandanel, R., Zanin, and J., Zapatero
Subjects: High energy, Supernova remnants, Astrophysics, Radiation, Power law, Coincident, Observacions astronòmiques, Supernova remnant, Gamma ray astronomy, Astronomia de raigs gamma, MAGIC (telescope), Physics, Supernoves, Astronomy, Astronomy and Astrophysics, Galactic plane, Very high energy gamma ray astronomy, Supernovae, MAGIC telescope, Space and Planetary Science, Very High Energy Gamma-ray Astronomy, Electrónica, Física nuclear, Electricidad, gamma rays: observations, Astronomical observations
Abstract: We report the detection of a new source of very high energy (VHE; E-gamma >= 100 GeV) gamma- ray emission located close to the Galactic plane, MAGIC J0616 + 225, which is spatially coincident with supernova remnant IC 443. The observations were carried out with the MAGIC telescope in the periods 2005 December-2006 January and 2006 December-2007 January. Here we present results from this source, leading to a VHE gamma-ray signal with a statistical significance of 5.7 sigma in the 2006/2007 data and a measured differential gamma-ray flux consistent with a power law, described as dN(gamma)/(dA dt dE) = (1.0 +/- 0.2) x 10(-11) (E/0.4 TeV)(-3.1 +/- 0.3) cm(-2) s(-1) TeV-1. We briefly discuss the observational technique used and the procedure implemented for the data analysis. The results are placed in the context of the multiwavelength emission and the molecular environment found in the region of IC 443.
Published: 2007

13. Constraints on the steady and pulsed very high energy gamma-ray emission from observations of PSR B1951+32/CTB 80 with the magic telescope

Author: Albert, J, Aliu, E, Anderhub, H, Antoranz, P, Armada, A, Baixeras, C, Barrio, Ja, Bartko, H, Bastieri, Denis, Becker, Jk, Bednarek, W, Berger, K, Bigongiari, C, Biland, A, Bock, Rk, Bordas, P, BOSCH RAMON, V, Bretz, T, Britvitch, I, Camara, M, Carmona, E, Chilingarian, A, Coarasa, Ja, Commichau, S, Contreras, Jl, Cortina, J, Costado, Mt, Curtef, V, Danielyan, V, Dazzi, Francesco, DE ANGELIS, A, Delgado, C, Reyes, Rdl, DE LOTTO, B, DOMINGO SANTAMARIA, E, Dorner, D, Doro, Michele, Errando, M, Fagiolini, M, Ferenc, D, Fernandez, E, Firpo, R, Flix, J, Fonseca, Mv, Font, L, Fuchs, M, Galante, N, GARCIA LOPEZ, R, Garczarczyk, M, Gaug, M, Giller, M, Goebel, F, Hakobyan, D, Hayashida, M, Hengstebeck, T, Herrero, A, Hirotani, K, Hne, Dhr, Hose, J, Hsu, Cc, Jacon, P, Jogler, T, Kosyra, R, Kranich, D, Kritzer, R, Laille, A, Lindfors, E, Lombardi, S, Longo, F, Lopez, J, Lopez, M, Lorenz, E, Majumdar, P, Maneva, G, Mannheim, K, Mansutti, O, Mariotti, Mose', Martinez, M, Mazin, D, Merck, C, Meucci, M, Meyer, M, Miranda, Jm, Mirzoyan, R, Mizobuchi, S, Moralejo, A, Nieto, D, Nilsson, K, Ninkovic, J, ONA WILHELMI, E, Otte, N, Oya, I, Paneque, D, Panniello, M, Paoletti, R, Paredes, Jm, Pasanen, M, Pascoli, Donatella, Pauss, F, Pegna, R, Persic, M, Peruzzo, Luigi, Piccioli, A, Poller, M, Prandini, E, Puchades, N, Raymers, A, Rhode, W, Ribo, M, Rico, J, Rissi, M, Robert, A, Gamer, Srr, Saggion, Antonio, Sanchez, A, Sartori, Paolo, Scalzotto, VILLI MARIO, Scapin, V, Schmitt, R, Schweizer, T, Shayduk, M, Shinozaki, K, Shore, Sn, Sidro, N, Sillanpaa, A, Sobczynska, D, Stamerra, A, Stark, Ls, Takalo, L, Temnikov, P, Tescaro, D, Teshima, M, Tonello, N, Torres, Df, Turini, N, Vankov, H, Vitale, V, Wagner, Rm, Wibig, T, Wittek, W, Zandanel, F, Zanin, R, Zapatero, J., J., Albert, E., Aliu, H., Anderhub, P., Antoranz, A., Armada, C., Baixera, J. A., Barrio, H., Bartko, D., Bastieri, J. K., Becker, W., Bednarek, K., Berger, C., Bigongiari, A., Biland, R. K., Bock, P., Borda, V., Bosch Ramon, T., Bretz, I., Britvitch, M., Camara, E., Carmona, A., Chilingarian, J. A., Coarasa, S., Commichau, J. L., Contrera, J., Cortina, M. T., Costado, V., Curtef, V., Danielyan, F., Dazzi, A. D., Angeli, C., Delgado, R. D. L., Reye, B. D., Lotto, E., Domingo Santamaria, D., Dorner, M., Doro, M., Errando, M., Fagiolini, D., Ferenc, E., Fernandez, R., Firpo, J., Flix, M. V., Fonseca, L., Font, M., Fuch, N., Galante, R., Garcia Lopez, M., Garczarczyk, M., Gaug, M., Giller, F., Goebel, D., Hakobyan, M., Hayashida, T., Hengstebeck, A., Herrero, K., Hirotani, D. H. R., Hne, J., Hose, C. C., Hsu, P., Jacon, T., Jogler, R., Kosyra, D., Kranich, R., Kritzer, A., Laille, E., Lindfor, S., Lombardi, Longo, Francesco, J., Lopez, M., Lopez, E., Lorenz, P., Majumdar, G., Maneva, K., Mannheim, O., Mansutti, M., Mariotti, M., Martinez, D., Mazin, C., Merck, M., Meucci, M., Meyer, J. M., Miranda, R., Mirzoyan, S., Mizobuchi, A., Moralejo, D., Nieto, K., Nilsson, J., Ninkovic, E., Ona Wilhelmi, N., Otte, I., Oya, D., Paneque, M., Panniello, R., Paoletti, J. M., Parede, M., Pasanen, D., Pascoli, F., Pau, R., Pegna, M., Persic, L., Peruzzo, A., Piccioli, M., Poller, E., Prandini, N., Puchade, A., Raymer, W., Rhode, M., Ribo, J., Rico, M., Rissi, A., Robert, S. R. R., Gamer, A., Saggion, A., Sanchez, P., Sartori, V., Scalzotto, V., Scapin, R., Schmitt, T., Schweizer, M., Shayduk, K., Shinozaki, S. N., Shore, N., Sidro, A., Sillanpaa, D., Sobczynska, A., Stamerra, L. S., Stark, L., Takalo, P., Temnikov, D., Tescaro, M., Teshima, N., Tonello, D. F., Torre, N., Turini, H., Vankov, V., Vitale, R. M., Wagner, T., Wibig, W., Wittek, F., Zandanel, R., Zanin, and J., Zapatero
Subjects: SUPERNOVA REMNANT CTB-80, CTB80, Very High Energy Gamma-ray Astronomy, Pulsar, Pulsar Wind Nebulae, MAGIC telescope, PSR B1951+32, gamma ray astronomy, Cosmic rays, IMAGING CHERENKOV DETECTOR, RAPIDLY SPINNING PULSARS, CRAB-NEBULA, GAPS, MAGNETOSPHERES, RADIATION, WIND NEBULAE, VELA-X
Abstract: We report on very high energy gamma-ray observations with the MAGIC Telescope of the pulsar PSR B1951+32 and its associated nebula, CTB 80. Our data constrain the cutoff energy of the pulsar to be less than 32 GeV, assuming the pulsed gamma-ray emission to be exponentially cut off. In the case that the cutoff follows a superexponential behavior, the cutoff energy can be as high as similar to 60 GeV. The upper limit on the flux of pulsed gamma-ray emission above 75 GeV is 4.3; 10(-11) photons cm(-2) s(-1), and the upper limit on the flux of steady emission above 140 GeV is 1.5; 10(-11) photons cm(-2) s(-1). We discuss our results in the framework of recent model predictions and other studies.
Published: 2007

14. Detection of very high energy radiation from the BL lacertae object PG 1553+113 with the MAGIC telescope

Author: Michela Fagiolini, Oriana Mansutti, Thomas Bretz, V. Scapin, V. Danielyan, T. Hengstebeck, Manel Errando, J. Zapatero, D. Tescaro, Wolfgang Rhode, N. Otte, Felicitas Pauss, Mario Meucci, Francesco Longo, W. Wittek, P. Jacon, M. Camara, H. Anderhub, Daniel Ferenc, C. Merck, Daniela Dorner, E. Aliu, M. V. Fonseca, M. Rissi, Riccardo Paoletti, Elina Lindfors, P. Sartori, H. Vankov, David Paneque, Mosè Mariotti, Denis Bastieri, Daniel Mazin, Masahiro Teshima, Dorota Sobczyńska, G. Maneva, C. C. Hsu, Maria Giller, Alvaro Sanchez, R. Schmitt, J. M. Paredes, Antonio Stamerra, R. G. Pegna, Justin Albert, A. Saggion, Karl Mannheim, L. Peruzzo, Tadeusz Wibig, Adrian Biland, Florian Goebel, Markus Gaug, Pol Bordas, R. Firpo, Saverio Lombardi, S. Rügamer, Juan Abel Barrio, C. Baixeras, E. Prandini, M. Garczarczyk, A. Armada, J. Rico, Stefano Ciprini, A. Robert, M. Poller, A. Sillanpää, Petar Temnikov, Julia Becker, K. Berger, S. Commichau, L. S. Stark, Wlodek Bednarek, R. Zanin, R. Mirzoyan, P. Antoranz, I. Britvitch, E. Oña-Wilhelmi, V. Curtef, M. A. Lopez, R. Kosyra, N. Puchades, Robert Wagner, J. Hose, K. Shinozaki, E. Carmona, P. Liebing, Masaaki Hayashida, M. Shayduk, V. Vitale, Jose Luis Contreras, D. Hakobyan, S. Mizobuchi, L. O. Takalo, Juan Cortina, Jose Miguel Miranda, E. Fernandez, A. Raymers, A. De Angelis, E. Domingo-Santamaría, N. Sidro, A. Laille, Marc Ribó, Valentí Bosch-Ramon, E. Lorenz, A. Piccioli, Ashot Chilingarian, O. Kalekin, D. Pascoli, Nicola Galante, T. Jogler, D. Höhne, P. Majumdar, R. de los Reyes, Nicola Turini, R. K. Bock, N. Tonello, Jorge Andres Lopez Lopez, T. Schweizer, Michele Doro, V. Scalzotto, Miriam Lucio Martinez, Igor Oya, Jose Flix, Daniel Kranich, Ll. Font, Kari Nilsson, Jelena Ninkovic, Francesco Dazzi, J. A. Coarasa, M. Fuchs, Massimo Persic, M. Meyer, Abelardo Moralejo, Diego F. Torres, Ciro Bigongiari, M. Pasanen, R. Kritzer, B. De Lotto, H. Bartko, J., Albert, E., Aliu, H., Anderhub, P., Antoranz, A., Armada, C., Baixera, J. A., Barrio, H., Bartko, D., Bastieri, J., Becker, W., Bednarek, K., Berger, C., Bigongiari, A., Biland, R. K., Bock, P., Borda, V., Bosch Raman, T., Bretz, I., Britvitch, M., Camara, E., Carmona, A., Chilingarian, S., Ciprini, J. A., Coarasa, S., Commichau, J. L., Contrera, J., Cortina, V., Curtef, V., Danielyan, F., Dazzi, A. D., Angeli, R. D. L., Reye, B. D., Lotto, E., Domingo Santamaria, D., Dorner, M., Doro, M., Errando, M., Fagiolini, D., Ferenc, E., Fernandez, R., Firpo, J., Flix, M. V., Fonseca, L., Font, M., Fuch, N., Galante, M., Garczarczyk, M., Gaug, M., Giller, F., Goebel, D., Hakobyan, M., Hayashida, T., Hengstebeck, D., Hohne, J., Hose, C. C., Hsu, P., Jacon, T., Jogler, O., Kalekin, R., Kosyra, D., Kranich, R., Kritzer, A., Laille, P., Liebing, E., Lindfor, S., Lombardi, Longo, Francesco, J., Lopez, M., Lopez, E., Lorenz, P., Majumdar, G., Maneva, K., Mannheim, O., Mansutti, M., Mariotti, M., Martinez, D., Mazin, C., Merck, M., Meucci, M., Meyer, J. M., Miranda, R., Mirzoyan, S., Mizobuchi, A., Moralejo, K., Nilsson, J., Ninkovic, E., Ona Wilhelmi, N., Otte, I., Oya, D., Paneque, R., Paoletti, J. M., Parede, M., Pasanen, D., Pascoli, F., Pau, R., Pegna, M., Persic, L., Peruzzo, A., Piccioli, M., Poller, N., Puchade, E., Prandini, A., Raymer, W., Rhode, M., Ribo, J., Rico, M., Rissi, A., Robert, S., Rugamer, A., Saggion, A., Sanchez, P., Sartori, V., Scalzotto, V., Scapin, R., Schmitt, T., Schweizer, M., Shayduk, K., Shinozaki, N., Sidro, A., Sillanpaa, D., Sobczynska, A., Stamerra, L. S., Stark, L., Takalo, P., Temnikov, D., Tescaro, M., Teshima, N., Tonello, D. F., Torre, N., Turini, H., Vankov, V., Vitale, R. M., Wagner, T., Wibig, W., Wittek, R., Zanin, and J., Zapatero
Subjects: Photon, Astrophysics::High Energy Astrophysical Phenomena, Flux, Astrophysics::Cosmology and Extragalactic Astrophysics, Astrophysics, Power law, Astronomical observatories, IMAGING CHERENKOV DETECTOR, gamma ray astronomy, Cosmic rays, Raigs gamma, Radiofrequency radiation, Physics, Gamma rays, Astronomy, Sigma, Astronomy and Astrophysics, Active Galactic Nuclei, Light curve, Redshift, MAGIC telescope, Space and Planetary Science, Very High Energy Gamma-ray Astronomy, BL Lacertae objects: individual (PG 1553+113), gamma rays: observations, Electrónica, Física nuclear, Electricidad, Observatoris astronòmics, BL Lac object
Abstract: In 2005 and 2006, the MAGIC telescope observed very high energy gamma-ray emission from the distant BL Lac object PG 1553 + 113. The overall significance of the signal was 8.8 sigma for 18.8 hr of observation time. The light curve shows no significant flux variations on a daily timescale; the flux level during 2005 was, however, significantly higher compared to 2006. The differential energy spectrum between similar to 90 and 500 GeV is well described by a power law with photon index. Gamma = 4.2 +/- 0.3. The combined 2005 and 2006 energy spectrum provides an upper limit of z = 0.74 on the redshift of the object.
Published: 2007

15. Transplant of Schwann cells allows normal development of the visual cortex of dark-reared rats

Author: Michela Fagiolini, MariaCristina Cenni, Lamberto Maffei, Tommaso Pizzorusso, Vittorio Porciatti, M., Fagiolini, Pizzorusso, Tommaso, V., Porciatti, M. C., Cenni, and L., Maffei
Subjects: Patch-Clamp Techniques, genetic structures, Cell Transplantation, Schwann cell, Receptors, Nerve Growth Factor, Membrane Potentials, Lateral ventricles, Neurotrophic factors, Orientation, medicine, Animals, Brain Tissue Transplantation, Nerve Growth Factors, Habituation, Visual Cortex, Vision, Binocular, biology, General Neuroscience, Darkness, eye diseases, Rats, Electrophysiology, Visual cortex, medicine.anatomical_structure, Animals, Newborn, Receptive field, biology.protein, Evoked Potentials, Visual, corteccia visiva, Schwann Cells, Visual Fields, Psychology, Neuroscience, Photic Stimulation, Neurotrophin
Abstract: Visual experience is necessary for the correct development of the visual cortex. Dark-rearing from birth affects normal maturation of the functional properties of mammalian visual cortex: cortical cells show rapid habituation to repeated stimulation, decreased orientation selectivity, and enlarged receptive fields. Spatial resolution and response latency are also impaired. Recent experiments have demonstrated that visual deprivation reduces the expression of neurotrophins in the visual cortex. We formulated the hypothesis that visual experience drives the maturation of functional properties of the visual cortex by regulating cortical levels of neurotrophins. If this hypothesis is correct, exogenous supply of neurotrophins during dark-rearing from birth should prevent, or at least ameliorate, the effects of a lack of visual experience. Since Schwann cells are efficient biological minipumps of neurotrophic factors, we transplanted 1.0 or 1.5 x 10(6) Schwann cells or infused vehicle solution as a control into the lateral ventricles of 13 day old rats reared in total darkness from birth until the end of the critical period (postnatal day 45). Single-cell responses and visual-evoked potentials were recorded from the binocular zone of the primary visual cortex of each group. We found that in Schwann cell-transplanted animals all parameters tested were significantly improved upon those of dark-reared control rats and were in the range of normal adult values. Thus, Schwann cell transplant contributed to the normal development of visual response properties in the visual cortex, compensating for a complete absence of visual experience.
Published: 1997

16. Early differential impact of MeCP2 mutations on functional networks in Rett syndrome patient-derived human cerebral organoids.

Author: Osaki T, Delepine C, Osako Y, Kranz D, Levin A, Nelson C, Fagiolini M, and Sur M
Abstract: Human cerebral organoids derived from induced pluripotent stem cells can recapture early developmental processes and reveal changes involving neurodevelopmental disorders. Mutations in the X-linked methyl-CpG binding protein 2 (MECP2) gene are associated with Rett syndrome, and disease severity varies depending on the location and type of mutation. Here, we focused on neuronal activity in Rett syndrome patient-derived organoids, analyzing two types of MeCP2 mutations - a missense mutation (R306C) and a truncating mutation (V247X) - using calcium imaging with three-photon microscopy. Compared to isogenic controls, we found abnormal neuronal activity in Rett organoids and altered network function based on graph theoretic analyses, with V247X mutations impacting functional responses and connectivity more severely than R306C mutations. These changes paralleled EEG data obtained from patients with comparable mutations. Labeling DLX promoter-driven inhibitory neurons demonstrated differences in activity and functional connectivity of inhibitory and excitatory neurons in the two types of mutation. Transcriptomic analyses revealed HDAC2-associated impairment in R306C organoids and decreased GABA A receptor expression in excitatory neurons in V247X organoids. These findings demonstrate mutation-specific mechanisms of vulnerability in Rett syndrome and suggest targeted strategies for their treatment.
Published: 2024
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17. CDKL5 sculpts functional callosal connectivity to promote cognitive flexibility.

Author: Awad PN, Zerbi V, Johnson-Venkatesh EM, Damiani F, Pagani M, Markicevic M, Nickles S, Gozzi A, Umemori H, and Fagiolini M
Subjects: Animals, Mice, Male, Female, Epileptic Syndromes genetics, Epileptic Syndromes physiopathology, Gyrus Cinguli metabolism, Spasms, Infantile genetics, Spasms, Infantile physiopathology, Spasms, Infantile metabolism, Cognitive Dysfunction physiopathology, Cognitive Dysfunction genetics, Cognitive Dysfunction metabolism, Neurodevelopmental Disorders genetics, Neurodevelopmental Disorders physiopathology, Neurodevelopmental Disorders metabolism, Disease Models, Animal, Neurons metabolism, X-Linked Intellectual Disability genetics, X-Linked Intellectual Disability physiopathology, Mice, Inbred C57BL, Brain metabolism, Synapses metabolism, Synapses physiology, Protein Serine-Threonine Kinases genetics, Protein Serine-Threonine Kinases metabolism, Corpus Callosum metabolism, Mice, Knockout, Cognition physiology, Magnetic Resonance Imaging methods
Abstract: Functional and structural connectivity alterations in short- and long-range projections have been reported across neurodevelopmental disorders (NDD). Interhemispheric callosal projection neurons (CPN) represent one of the major long-range projections in the brain, which are particularly important for higher-order cognitive function and flexibility. However, whether a causal relationship exists between interhemispheric connectivity alterations and cognitive deficits in NDD remains elusive. Here, we focused on CDKL5 Deficiency Disorder (CDD), a severe neurodevelopmental disorder caused by mutations in the X-linked Cyclin-dependent kinase-like 5 (CDKL5) gene. We found an increase in homotopic interhemispheric connectivity and functional hyperconnectivity across higher cognitive areas in adult male and female CDKL5-deficient mice by resting-state functional MRI (rs-fMRI) analysis. This was accompanied by an increase in the number of callosal synaptic inputs but decrease in local synaptic connectivity in the cingulate cortex of juvenile CDKL5-deficient mice, suggesting an impairment in excitatory synapse development and a differential role of CDKL5 across excitatory neuron subtypes. These deficits were associated with significant cognitive impairments in CDKL5 KO mice. Selective deletion of CDKL5 in the largest subtype of CPN likewise resulted in an increase of functional callosal inputs, without however significantly altering intracortical cingulate networks. Notably, such callosal-specific changes were sufficient to cause cognitive deficits. Finally, when CDKL5 was selectively re-expressed only in this CPN subtype, in otherwise CDKL5-deficient mice, it was sufficient to prevent the cognitive impairments of CDKL5 mutants. Together, these results reveal a novel role of CDKL5 by demonstrating that it is both necessary and sufficient for proper CPN connectivity and cognitive function and flexibility, and further validates a causal relationship between CPN dysfunction and cognitive impairment in a model of NDD., (© 2023. The Author(s).)
Published: 2024
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18. Phenotypic characterization of Cdkl5-knockdown neurons establishes elongated cilia as a functional assay for CDKL5 Deficiency Disorder.

Author: Di Nardo A, Rühmkorf A, Award P, Brennecke A, Fagiolini M, and Sahin M
Subjects: Animals, Cilia, Mice, Neurons, Phenotype, Epileptic Syndromes genetics, Protein Serine-Threonine Kinases genetics
Abstract: CDKL5 Deficiency Disorder (CDD) is a severe encephalopathy characterized by intractable epilepsy, infantile spasms, and cognitive disabilities. The detrimental CNS manifestations and lack of therapeutic interventions represent unmet needs, necessitating identification of CDD-dependent phenotypes for in vitro disease modeling and therapeutic testing. Here, we optimized a high-content assay to quantify cilia in CDKL5-deficient neurons. Our work shows that Cdkl5-knockdown neurons have elongated cilia and uncovers cilium lengthening in hippocampi of Cdkl5 knockout mice. Collectively, our findings identify cilia length alterations under CDKL5 activity loss in vitro and in vivo and reveal elongated cilia as a robust functional phenotype for CDD., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)
Published: 2022
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19. Brain mapping across 16 autism mouse models reveals a spectrum of functional connectivity subtypes.

Author: Zerbi V, Pagani M, Markicevic M, Matteoli M, Pozzi D, Fagiolini M, Bozzi Y, Galbusera A, Scattoni ML, Provenzano G, Banerjee A, Helmchen F, Basson MA, Ellegood J, Lerch JP, Rudin M, Gozzi A, and Wenderoth N
Subjects: Animals, Brain, Brain Mapping, Magnetic Resonance Imaging, Mice, Neural Pathways, Autism Spectrum Disorder diagnostic imaging, Autism Spectrum Disorder genetics, Autistic Disorder diagnostic imaging, Autistic Disorder genetics
Abstract: Autism Spectrum Disorder (ASD) is characterized by substantial, yet highly heterogeneous abnormalities in functional brain connectivity. However, the origin and significance of this phenomenon remain unclear. To unravel ASD connectopathy and relate it to underlying etiological heterogeneity, we carried out a bi-center cross-etiological investigation of fMRI-based connectivity in the mouse, in which specific ASD-relevant mutations can be isolated and modeled minimizing environmental contributions. By performing brain-wide connectivity mapping across 16 mouse mutants, we show that different ASD-associated etiologies cause a broad spectrum of connectional abnormalities in which diverse, often diverging, connectivity signatures are recognizable. Despite this heterogeneity, the identified connectivity alterations could be classified into four subtypes characterized by discrete signatures of network dysfunction. Our findings show that etiological variability is a key determinant of connectivity heterogeneity in ASD, hence reconciling conflicting findings in clinical populations. The identification of etiologically-relevant connectivity subtypes could improve diagnostic label accuracy in the non-syndromic ASD population and paves the way for personalized treatment approaches., (© 2021. The Author(s).)
Published: 2021
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20. Dynamical Characteristics of Wild-Type Mouse Spontaneous Pupillary Fluctuations .

Author: Sviridova N, Artoni P, Fagiolini M, Hensch TK, and Aihara K
Subjects: Animals, Healthy Volunteers, Humans, Mice, Pupil
Abstract: Spontaneous pupil size fluctuations in humans and mouse models are noninvasively measured data that can be used for early detection of neurodevelopmental spectrum disorders. While highly valuable in such applied studies, pupillometry dynamics and dynamical characteristics have not been fully investigated, although their understanding may potentially lead to the discovery of new information, which cannot be readily uncovered by conventional methods. Properties of pupillometry dynamics, such as determinism, were previously investigated for healthy human subjects; however, the dynamical characteristics of pupillometry data in mouse models, and whether they are similar to those of human subjects, remain largely unknown. Therefore, it is necessary to establish a thorough understanding of the dynamical properties of mouse pupillometry dynamics and to clarify whether it is similar to that of humans. In this study, dynamical pupillometry characteristics from 115 wild-type mouse datasets were investigated by methods of nonlinear time series analysis. Results clearly demonstrated a strong underlying determinism in the investigated data. Additionally, the data's trajectory divergence rate and predictability were estimated.
Published: 2021
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21. Visual Dysfunction after Repetitive Mild Traumatic Brain Injury in a Mouse Model and Ramifications on Behavioral Metrics.

Author: Morriss NJ, Conley GM, Hodgson N, Boucher M, Ospina-Mora S, Fagiolini M, Puder M, Mejia L, Qiu J, Meehan W, and Mannix R
Subjects: Animals, Brain Concussion physiopathology, Brain Concussion psychology, Cognition, Conditioning, Operant, Electroretinography, Evoked Potentials, Visual, Learning, Male, Maze Learning, Memory, Mice, Mice, Inbred C57BL, Optic Nerve Injuries physiopathology, Optic Nerve Injuries psychology, Psychomotor Performance, Recurrence, Retina injuries, Retina pathology, Vision Disorders physiopathology, Vision Disorders psychology, Visual Acuity, Visual Pathways physiopathology, Behavior, Animal, Brain Concussion complications, Vision Disorders etiology
Abstract: Mild traumatic brain injury (mTBI) is a major cause of morbidity and mortality with a poorly understood pathophysiology. Animal models have been increasingly utilized to better understand mTBI and recent research has identified visual deficits in these models that correspond to human literature. While visual impairment is being further characterized within TBI, the implications of impaired vision on behavioral tasks commonly utilized in animal models has not been well described thus far. Visual deficits may well confound behavioral tests that are believed to be isolated to cognitive functioning such as learning and memory. We utilized a mouse model of repetitive mTBI (rmTBI) to further characterize visual deficits using an optomotor task, electroretinogram, and visually evoked potential, and located likely areas of damage to the visual pathway. Mice were tested on multiple behavioral metrics, including a touchscreen conditional learning task to better identify the contribution of visual dysfunction to behavioral alterations. We found that rmTBI caused visual dysfunction resulting from damage distal to the retina that likely involves pathology within the optic nerve. Moreover, loss of vision led to poorer performance of rmTBI animals on classic behavioral tests such as the Morris water maze that would otherwise be attributed solely to learning and memory deficits. The touchscreen conditional learning task was able to differentiate rmTBI induced learning and memory dysfunction from visual impairment and is a valuable tool for elucidating subtle changes resulting from TBI.
Published: 2021
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22. Animal Models of Neurodevelopmental Disorders.

Author: Bozzi Y and Fagiolini M
Subjects: Animals, Disease Models, Animal, Neurodevelopmental Disorders
Published: 2020
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23. Intellectual and Developmental Disabilities Research Centers: A Multidisciplinary Approach to Understand the Pathogenesis of Methyl-CpG Binding Protein 2-related Disorders.

Author: Fagiolini M, Patrizi A, LeBlanc J, Jin LW, Maezawa I, Sinnett S, Gray SJ, Molholm S, Foxe JJ, Johnston MV, Naidu S, Blue M, Hossain A, Kadam S, Zhao X, Chang Q, Zhou Z, and Zoghbi H
Subjects: Carrier Proteins, Child, Developmental Disabilities, Humans, Mutation, Reproducibility of Results, Methyl-CpG-Binding Protein 2 genetics, Methyl-CpG-Binding Protein 2 metabolism, Rett Syndrome genetics
Abstract: Disruptions in the gene encoding methyl-CpG binding protein 2 (MECP2) underlie complex neurodevelopmental disorders including Rett Syndrome (RTT), MECP2 duplication disorder, intellectual disabilities, and autism. Significant progress has been made on the molecular and cellular basis of MECP2-related disorders providing a new framework for understanding how altered epigenetic landscape can derail the formation and refinement of neuronal circuits in early postnatal life and proper neurological function. This review will summarize selected major findings from the past years and particularly highlight the integrated and multidisciplinary work done at eight NIH-funded Intellectual and Developmental Disabilities Research Centers (IDDRC) across the US. Finally, we will outline a path forward with identification of reliable biomarkers and outcome measures, longitudinal preclinical and clinical studies, reproducibility of results across centers as a synergistic effort to decode and treat the pathogenesis of the complex MeCP2 disorders., (Copyright © 2020. Published by Elsevier Ltd.)
Published: 2020
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24. Deep learning of spontaneous arousal fluctuations detects early cholinergic defects across neurodevelopmental mouse models and patients.

Author: Artoni P, Piffer A, Vinci V, LeBlanc J, Nelson CA, Hensch TK, and Fagiolini M
Subjects: Animals, Autistic Disorder genetics, Autistic Disorder metabolism, Autistic Disorder physiopathology, Cohort Studies, Disease Models, Animal, Female, Humans, Male, Methyl-CpG-Binding Protein 2 genetics, Methyl-CpG-Binding Protein 2 metabolism, Mice, Protein Serine-Threonine Kinases genetics, Protein Serine-Threonine Kinases metabolism, Pupil physiology, Rett Syndrome genetics, Rett Syndrome metabolism, Rett Syndrome physiopathology, Rett Syndrome psychology, Acetylcholine metabolism, Arousal, Autistic Disorder psychology, Deep Learning
Abstract: Neurodevelopmental spectrum disorders like autism (ASD) are diagnosed, on average, beyond age 4 y, after multiple critical periods of brain development close and behavioral intervention becomes less effective. This raises the urgent need for quantitative, noninvasive, and translational biomarkers for their early detection and tracking. We found that both idiopathic (BTBR) and genetic (CDKL5- and MeCP2-deficient) mouse models of ASD display an early, impaired cholinergic neuromodulation as reflected in altered spontaneous pupil fluctuations. Abnormalities were already present before the onset of symptoms and were rescued by the selective expression of MeCP2 in cholinergic circuits. Hence, we trained a neural network (ConvNetACh) to recognize, with 97% accuracy, patterns of these arousal fluctuations in mice with enhanced cholinergic sensitivity (LYNX1-deficient). ConvNetACh then successfully detected impairments in all ASD mouse models tested except in MeCP2-rescued mice. By retraining only the last layers of ConvNetACh with heart rate variation data (a similar proxy of arousal) directly from Rett syndrome patients, we generated ConvNetPatients, a neural network capable of distinguishing them from typically developing subjects. Even with small cohorts of rare patients, our approach exhibited significant accuracy before (80% in the first and second year of life) and into regression (88% in stage III patients). Thus, transfer learning across species and modalities establishes spontaneous arousal fluctuations combined with deep learning as a robust noninvasive, quantitative, and sensitive translational biomarker for the rapid and early detection of neurodevelopmental disorders before major symptom onset., Competing Interests: The authors declare no conflict of interest.
Published: 2020
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25. The Stage of the Estrus Cycle Is Critical for Interpretation of Female Mouse Social Interaction Behavior.

Author: Chari T, Griswold S, Andrews NA, and Fagiolini M
Abstract: Female animals in biomedical research have traditionally been excluded from research studies due to the perceived added complexity caused by the estrus cycle. However, given the importance of sex differences in a variety of neurological disorders, testing female mice is critical to identifying sex-linked effects in diseases. To determine the susceptibility of simple behaviors to hormonal fluctuations in the estrus cycle, we studied the effects of sex and the estrus cycle on a variety of behavioral tasks commonly used in mouse phenotyping laboratories. Male and female C57BL/6J mice were tested in a small battery of short duration tests and, immediately on completion of each test, females were classified using cytology of vaginal lavages as sexually-receptive (proestrus and estrus) or non-receptive (NR; metestrus and diestrus). We showed that there was a significant difference in 3-chamber social interaction (SI) between female mice at different stages of their estrus cycle, with sexually-receptive mice showing no preferential interest in a novel female mouse compared with an empty chamber. NR female mice showed the same level of preference for a novel female mouse as male mice did for a novel male mouse. No differences between or within sexes were found for tests of anxiety elevated plus maze (EPM; Hole board), working memory [Novel object recognition (NOR)], and motor learning (repeated tests on rotarod). We conclude that the stage of the estrus cycle may impact SI between same-sex conspecifics, and does not impact performance in the elevated plus-maze, hole board, NOR, and rotarod., (Copyright © 2020 Chari, Griswold, Andrews and Fagiolini.)
Published: 2020
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26. Accelerated Hyper-Maturation of Parvalbumin Circuits in the Absence of MeCP2.

Author: Patrizi A, Awad PN, Chattopadhyaya B, Li C, Di Cristo G, and Fagiolini M
Subjects: Animals, GABAergic Neurons cytology, Interneurons cytology, Interneurons physiology, Male, Methyl-CpG-Binding Protein 2 genetics, Mice, Inbred C57BL, Mice, Knockout, Neural Pathways cytology, Neural Pathways growth & development, Visual Cortex cytology, GABAergic Neurons physiology, Methyl-CpG-Binding Protein 2 physiology, Parvalbumins physiology, Visual Cortex growth & development
Abstract: Methyl-CpG-binding protein 2 (MeCP2) mutations are the primary cause of Rett syndrome, a severe neurodevelopmental disorder. Cortical parvalbumin GABAergic interneurons (PV) make exuberant somatic connections onto pyramidal cells in the visual cortex of Mecp2-deficient mice, which contributes to silencing neuronal cortical circuits. This phenotype can be rescued independently of Mecp2 by environmental, pharmacological, and genetic manipulation. It remains unknown how Mecp2 mutation can result in abnormal inhibitory circuit refinement. In the present manuscript, we examined the development of GABAergic circuits in the primary visual cortex of Mecp2-deficient mice. We identified that PV circuits were the only GABAergic interneurons to be upregulated, while other interneurons were downregulated. Acceleration of PV cell maturation was accompanied by increased PV cells engulfment by perineuronal nets (PNNs) and by an increase of PV cellular and PNN structural complexity. Interestingly, selective deletion of Mecp2 from PV cells was sufficient to drive increased structure complexity of PNN. Moreover, the accelerated PV and PNN maturation was recapitulated in organotypic cultures. Our results identify a specific timeline of disruption of GABAergic circuits in the absence of Mecp2, indicating a possible cell-autonomous role of MeCP2 in the formation of PV cellular arbors and PNN structures in the visual cortex., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Published: 2020
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27. MeCP2: an epigenetic regulator of critical periods.

Author: Picard N and Fagiolini M
Subjects: Animals, Epigenesis, Genetic, Humans, Methyl-CpG-Binding Protein 2, Mice, Rett Syndrome
Abstract: Complex adult behaviors arise from the integration of sequential and often overlapping critical periods (CPs) early in life and adolescence. These processes rely on a subtle interplay between the set of genes inherited from the parents, the surrounding environment and epigenetic regulation. Methyl-CpG-binding protein 2 (MeCP2) has been shown to recognize epigenetic states and regulate gene expression by reading methylated DNA. Here, we will review the recent findings revealing the role of MeCP2 during postnatal CPs of development using mouse models of Rett (RTT) syndrome., (Copyright © 2019. Published by Elsevier Ltd.)
Published: 2019
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28. Behavioral analyses of animal models of intellectual and developmental disabilities.

Author: Crawley JN, Fagiolini M, Harrison FE, Samaco R, Wozniak DF, and Robinson MB
Subjects: Animals, Developmental Disabilities etiology, Humans, Intellectual Disability etiology, Developmental Disabilities psychology, Disease Models, Animal, Intellectual Disability psychology
Abstract: Intellectual and developmental disabilities (IDDs) are a common group of disorders that frequently share overlapping symptoms, including cognitive deficits, altered attention, seizures, impaired social interactions, and anxiety. The causes of these disorders are varied ranging from early prenatal/postnatal insults to genetic variants that either cause or are associated with an increased likelihood of an IDD. As many of the symptoms observed in individuals with IDDs are a manifestation of altered nervous system function resulting in altered behaviors, it should not be surprising that the field is very dependent upon in vivo model systems. This special issue of Neurobiology of Learning and Memory is focused on the methods and approaches that are being used to model and understand these disorders in mammals. While surveys by the Pew Foundation continue to find a high degree of confidence/trust in scientists by the public, several recent studies have documented issues with reproducibility in scientific publications. This special issue includes both primary research articles and review articles in which careful attention has been made to transparently report methods and use rigorous approaches to ensure reproducibility. Although there have been and will continue to be remarkable advances for treatment of subset of IDDs, it is clear that this field is still in its early stages. There is no doubt that the strategies being used to model IDDs will continue to evolve. We hope this special issue will support this evolution so that we can maintain the trust of the public and elected officials, and continue developing evidence-based approaches to new therapeutics., (Copyright © 2019 Elsevier Inc. All rights reserved.)
Published: 2019
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29. Rigor and reproducibility in rodent behavioral research.

Author: Gulinello M, Mitchell HA, Chang Q, Timothy O'Brien W, Zhou Z, Abel T, Wang L, Corbin JG, Veeraragavan S, Samaco RC, Andrews NA, Fagiolini M, Cole TB, Burbacher TM, and Crawley JN
Subjects: Animals, Behavioral Research standards, Reproducibility of Results, Research Design, Behavioral Research methods, Mice psychology, Rats psychology
Abstract: Behavioral neuroscience research incorporates the identical high level of meticulous methodologies and exacting attention to detail as all other scientific disciplines. To achieve maximal rigor and reproducibility of findings, well-trained investigators employ a variety of established best practices. Here we explicate some of the requirements for rigorous experimental design and accurate data analysis in conducting mouse and rat behavioral tests. Novel object recognition is used as an example of a cognitive assay which has been conducted successfully with a range of methods, all based on common principles of appropriate procedures, controls, and statistics. Directors of Rodent Core facilities within Intellectual and Developmental Disabilities Research Centers contribute key aspects of their own novel object recognition protocols, offering insights into essential similarities and less-critical differences. Literature cited in this review article will lead the interested reader to source papers that provide step-by-step protocols which illustrate optimized methods for many standard rodent behavioral assays. Adhering to best practices in behavioral neuroscience will enhance the value of animal models for the multiple goals of understanding biological mechanisms, evaluating consequences of genetic mutations, and discovering efficacious therapeutics., (Copyright © 2018 Elsevier Inc. All rights reserved.)
Published: 2019
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30. NMDA 2A receptors in parvalbumin cells mediate sex-specific rapid ketamine response on cortical activity.

Author: Picard N, Takesian AE, Fagiolini M, and Hensch TK
Subjects: Animals, Estrous Cycle drug effects, Female, Interneurons metabolism, Interneurons physiology, Male, Mice, Mice, Inbred C57BL, N-Methylaspartate metabolism, Parvalbumins metabolism, Prefrontal Cortex metabolism, Receptors, GABA-A metabolism, Receptors, N-Methyl-D-Aspartate metabolism, Sex Factors, Ketamine metabolism, Ketamine pharmacology, Receptors, N-Methyl-D-Aspartate physiology
Abstract: Ketamine has emerged as a widespread treatment for a variety of psychiatric disorders when used at sub-anesthetic doses, but the neural mechanisms underlying its acute action remain unclear. Here, we identified NMDA receptors containing the 2A subunit (GluN2A) on parvalbumin (PV)-expressing inhibitory interneurons as a pivotal target of low-dose ketamine. Genetically deleting GluN2A receptors globally or selectively from PV interneurons abolished the rapid enhancement of visual cortical responses and gamma-band oscillations by ketamine. Moreover, during the follicular phase of the estrous cycle in female mice, the ketamine response was transiently attenuated along with a concomitant decrease of grin2A mRNA expression within PV interneurons. Thus, GluN2A receptors on PV interneurons mediate the immediate actions of low-dose ketamine treatment, and fluctuations in receptor expression across the estrous cycle may underlie sex-differences in drug efficacy.
Published: 2019
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31. Transparent, Flexible, Penetrating Microelectrode Arrays with Capabilities of Single-Unit Electrophysiology.

Author: Seo KJ, Artoni P, Qiang Y, Zhong Y, Han X, Shi Z, Yao W, Fagiolini M, and Fang H
Subjects: Animals, Equipment Design, Materials Testing, Mice, Mice, Inbred C57BL, Neurons physiology, Pliability, Visual Cortex physiology, Electrodes, Implanted, Electrophysiology instrumentation, Microelectrodes
Abstract: Accurately mapping neuronal activity across brain networks is critical to understand behaviors, yet it is very challenging due to the need of tools with both high spatial and temporal resolutions. Here, penetrating arrays of flexible microelectrodes made of low-impedance nanomeshes are presented, which are capable of recording single-unit electrophysiological neuronal activity and at the same time, transparent, allowing to bridge electrical and optical brain mapping modalities. These 32 transparent penetrating electrodes with site area, 225 µm 2 , have a low impedance of ≈149 kΩ at 1 kHz, an adequate charge injection limit of ≈0.76 mC cm -2 , and up to 100% yield. Mechanical bending tests reveal that the array is robust up to 1000 bending cycles, and its high transmittance of 67% at 550 nm makes it suitable for combining with various optical methods. A temporary stiffening using polyethylene glycol allows the penetrating nanomesh arrays to be inserted into the brain minimally invasively, with in vivo validation of recordings of spontaneous and evoked single-unit activity of neurons across layers of the mouse visual cortex. Together, these results establish a novel neurotechnology-transparent, flexible, penetrating microelectrode arrays-which possesses great potential for brain research., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Published: 2019
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32. A Diet With Docosahexaenoic and Arachidonic Acids as the Sole Source of Polyunsaturated Fatty Acids Is Sufficient to Support Visual, Cognitive, Motor, and Social Development in Mice.

Author: Carlson SJ, O'Loughlin AA, Anez-Bustillos L, Baker MA, Andrews NA, Gunner G, Dao DT, Pan A, Nandivada P, Chang M, Cowan E, Mitchell PD, Gura KM, Fagiolini M, and Puder M
Abstract: Polyunsaturated fatty acids serve multiple functions in neurodevelopment and neurocognitive function. Intravenous lipid emulsions are administered to children that are dependent on parenteral nutrition to provide the essential fatty acids needed to sustain growth and development. One of these emulsions, derived from fish-oil, is particularly poor in the traditional essential fatty acids, linoleic and alpha-linolenic acids. However, it does contain adequate amounts of its main derivatives, arachidonic acid (ARA) and docosahexaenoic acid (DHA), respectively. This skewed composition has raised concern about the sole use of fish-oil based lipid emulsions in children and how its administration can be detrimental to their neurodevelopment. Using a custom-made diet that contains ARA and DHA as a sole source of polyunsaturated fatty acids, we bred and fed mice for multiple generations. Compared to adult, chow-fed mice, animals maintained on this special diet showed similar outcomes in a battery of neurocognitive tests performed under controlled conditions. Chow-fed mice did perform better in the rotarod test for ataxia and balance, although both experimental groups showed a conserved motor learning capacity. Conversely, mice fed the custom diet rich in DHA and ARA showed less neophobia than the chow-fed animals. Results from these experiments suggest that providing a diet where ARA and DHA are the sole source of polyunsaturated fatty acids is sufficient to support gross visual, cognitive, motor, and social development in mice.
Published: 2019
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33. Transparent arrays of bilayer-nanomesh microelectrodes for simultaneous electrophysiology and two-photon imaging in the brain.

Author: Qiang Y, Artoni P, Seo KJ, Culaclii S, Hogan V, Zhao X, Zhong Y, Han X, Wang PM, Lo YK, Li Y, Patel HA, Huang Y, Sambangi A, Chu JSV, Liu W, Fagiolini M, and Fang H
Subjects: Animals, Calcium analysis, Dielectric Spectroscopy instrumentation, Dielectric Spectroscopy methods, Electrodes, Implanted, Electrophysiology methods, Gold chemistry, Male, Mice, Inbred C57BL, Molecular Imaging, Photic Stimulation, Photons, Polystyrenes chemistry, Thiophenes chemistry, Visual Cortex diagnostic imaging, Visual Cortex physiology, Wireless Technology, Brain diagnostic imaging, Brain physiology, Electrophysiology instrumentation, Microelectrodes, Nanostructures chemistry
Abstract: Transparent microelectrode arrays have emerged as increasingly important tools for neuroscience by allowing simultaneous coupling of big and time-resolved electrophysiology data with optically measured, spatially and type resolved single neuron activity. Scaling down transparent electrodes to the length scale of a single neuron is challenging since conventional transparent conductors are limited by their capacitive electrode/electrolyte interface. In this study, we establish transparent microelectrode arrays with high performance, great biocompatibility, and comprehensive in vivo validations from a recently developed, bilayer-nanomesh material composite, where a metal layer and a low-impedance faradaic interfacial layer are stacked reliably together in a same transparent nanomesh pattern. Specifically, flexible arrays from 32 bilayer-nanomesh microelectrodes demonstrated near-unity yield with high uniformity, excellent biocompatibility, and great compatibility with state-of-the-art wireless recording and real-time artifact rejection system. The electrodes are highly scalable, with 130 kilohms at 1 kHz at 20 μm in diameter, comparable to the performance of microelectrodes in nontransparent Michigan arrays. The highly transparent, bilayer-nanomesh microelectrode arrays allowed in vivo two-photon imaging of single neurons in layer 2/3 of the visual cortex of awake mice, along with high-fidelity, simultaneous electrical recordings of visual-evoked activity, both in the multi-unit activity band and at lower frequencies by measuring the visual-evoked potential in the time domain. Together, these advances reveal the great potential of transparent arrays from bilayer-nanomesh microelectrodes for a broad range of utility in neuroscience and medical practices.
Published: 2018
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34. FANTOM5 CAGE profiles of human and mouse samples.

Author: Noguchi S, Arakawa T, Fukuda S, Furuno M, Hasegawa A, Hori F, Ishikawa-Kato S, Kaida K, Kaiho A, Kanamori-Katayama M, Kawashima T, Kojima M, Kubosaki A, Manabe RI, Murata M, Nagao-Sato S, Nakazato K, Ninomiya N, Nishiyori-Sueki H, Noma S, Saijyo E, Saka A, Sakai M, Simon C, Suzuki N, Tagami M, Watanabe S, Yoshida S, Arner P, Axton RA, Babina M, Baillie JK, Barnett TC, Beckhouse AG, Blumenthal A, Bodega B, Bonetti A, Briggs J, Brombacher F, Carlisle AJ, Clevers HC, Davis CA, Detmar M, Dohi T, Edge ASB, Edinger M, Ehrlund A, Ekwall K, Endoh M, Enomoto H, Eslami A, Fagiolini M, Fairbairn L, Farach-Carson MC, Faulkner GJ, Ferrai C, Fisher ME, Forrester LM, Fujita R, Furusawa JI, Geijtenbeek TB, Gingeras T, Goldowitz D, Guhl S, Guler R, Gustincich S, Ha TJ, Hamaguchi M, Hara M, Hasegawa Y, Herlyn M, Heutink P, Hitchens KJ, Hume DA, Ikawa T, Ishizu Y, Kai C, Kawamoto H, Kawamura YI, Kempfle JS, Kenna TJ, Kere J, Khachigian LM, Kitamura T, Klein S, Klinken SP, Knox AJ, Kojima S, Koseki H, Koyasu S, Lee W, Lennartsson A, Mackay-Sim A, Mejhert N, Mizuno Y, Morikawa H, Morimoto M, Moro K, Morris KJ, Motohashi H, Mummery CL, Nakachi Y, Nakahara F, Nakamura T, Nakamura Y, Nozaki T, Ogishima S, Ohkura N, Ohno H, Ohshima M, Okada-Hatakeyama M, Okazaki Y, Orlando V, Ovchinnikov DA, Passier R, Patrikakis M, Pombo A, Pradhan-Bhatt S, Qin XY, Rehli M, Rizzu P, Roy S, Sajantila A, Sakaguchi S, Sato H, Satoh H, Savvi S, Saxena A, Schmidl C, Schneider C, Schulze-Tanzil GG, Schwegmann A, Sheng G, Shin JW, Sugiyama D, Sugiyama T, Summers KM, Takahashi N, Takai J, Tanaka H, Tatsukawa H, Tomoiu A, Toyoda H, van de Wetering M, van den Berg LM, Verardo R, Vijayan D, Wells CA, Winteringham LN, Wolvetang E, Yamaguchi Y, Yamamoto M, Yanagi-Mizuochi C, Yoneda M, Yonekura Y, Zhang PG, Zucchelli S, Abugessaisa I, Arner E, Harshbarger J, Kondo A, Lassmann T, Lizio M, Sahin S, Sengstag T, Severin J, Shimoji H, Suzuki M, Suzuki H, Kawai J, Kondo N, Itoh M, Daub CO, Kasukawa T, Kawaji H, Carninci P, Forrest ARR, and Hayashizaki Y
Subjects: Animals, Gene Expression Regulation, Humans, Mice, Promoter Regions, Genetic, Species Specificity, Gene Expression Profiling, Genome
Abstract: In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples, consisting of a variety of primary cells, tissues, cell lines, and time series samples during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities.
Published: 2017
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35. A defect in myoblast fusion underlies Carey-Fineman-Ziter syndrome.

Author: Di Gioia SA, Connors S, Matsunami N, Cannavino J, Rose MF, Gilette NM, Artoni P, de Macena Sobreira NL, Chan WM, Webb BD, Robson CD, Cheng L, Van Ryzin C, Ramirez-Martinez A, Mohassel P, Leppert M, Scholand MB, Grunseich C, Ferreira CR, Hartman T, Hayes IM, Morgan T, Markie DM, Fagiolini M, Swift A, Chines PS, Speck-Martins CE, Collins FS, Jabs EW, Bönnemann CG, Olson EN, Carey JC, Robertson SP, Manoli I, and Engle EC
Subjects: Adult, Amino Acid Sequence, Animals, Cell Fusion, Child, Disease Models, Animal, Embryo, Nonmammalian, Female, Gene Expression, Genes, Recessive, Genetic Complementation Test, Humans, Infant, Male, Membrane Proteins deficiency, Mobius Syndrome metabolism, Mobius Syndrome pathology, Muscle Proteins deficiency, Muscle, Skeletal growth & development, Muscle, Skeletal pathology, Muscular Diseases metabolism, Muscular Diseases pathology, Myoblasts pathology, Pedigree, Pierre Robin Syndrome metabolism, Pierre Robin Syndrome pathology, Sequence Alignment, Sequence Homology, Amino Acid, Zebrafish, Zebrafish Proteins deficiency, Membrane Proteins genetics, Mobius Syndrome genetics, Morphogenesis genetics, Muscle Proteins genetics, Muscle, Skeletal metabolism, Muscular Diseases genetics, Mutation, Myoblasts metabolism, Pierre Robin Syndrome genetics, Zebrafish Proteins genetics
Abstract: Multinucleate cellular syncytial formation is a hallmark of skeletal muscle differentiation. Myomaker, encoded by Mymk (Tmem8c), is a well-conserved plasma membrane protein required for myoblast fusion to form multinucleated myotubes in mouse, chick, and zebrafish. Here, we report that autosomal recessive mutations in MYMK (OMIM 615345) cause Carey-Fineman-Ziter syndrome in humans (CFZS; OMIM 254940) by reducing but not eliminating MYMK function. We characterize MYMK-CFZS as a congenital myopathy with marked facial weakness and additional clinical and pathologic features that distinguish it from other congenital neuromuscular syndromes. We show that a heterologous cell fusion assay in vitro and allelic complementation experiments in mymk knockdown and mymk insT/insT zebrafish in vivo can differentiate between MYMK wild type, hypomorphic and null alleles. Collectively, these data establish that MYMK activity is necessary for normal muscle development and maintenance in humans, and expand the spectrum of congenital myopathies to include cell-cell fusion deficits.
Published: 2017
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36. Cortical Feedback Regulates Feedforward Retinogeniculate Refinement.

Author: Thompson AD, Picard N, Min L, Fagiolini M, and Chen C
Subjects: Animals, Clozapine analogs & derivatives, Clozapine pharmacology, Critical Period, Psychological, Geniculate Bodies drug effects, Mice, Muscimol pharmacology, Retinal Ganglion Cells physiology, Visual Cortex drug effects, Visual Pathways drug effects, Visual Pathways growth & development, Feedback, Physiological physiology, Geniculate Bodies physiology, Visual Cortex physiology, Visual Pathways physiology
Abstract: According to the prevailing view of neural development, sensory pathways develop sequentially in a feedforward manner, whereby each local microcircuit refines and stabilizes before directing the wiring of its downstream target. In the visual system, retinal circuits are thought to mature first and direct refinement in the thalamus, after which cortical circuits refine with experience-dependent plasticity. In contrast, we now show that feedback from cortex to thalamus critically regulates refinement of the retinogeniculate projection during a discrete window in development, beginning at postnatal day 20 in mice. Disrupting cortical activity during this window, pharmacologically or chemogenetically, increases the number of retinal ganglion cells innervating each thalamic relay neuron. These results suggest that primary sensory structures develop through the concurrent and interdependent remodeling of subcortical and cortical circuits in response to sensory experience, rather than through a simple feedforward process. Our findings also highlight an unexpected function for the corticothalamic projection., (Copyright © 2016 Elsevier Inc. All rights reserved.)
Published: 2016
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37. Chronic Administration of the N-Methyl-D-Aspartate Receptor Antagonist Ketamine Improves Rett Syndrome Phenotype.

Author: Patrizi A, Picard N, Simon AJ, Gunner G, Centofante E, Andrews NA, and Fagiolini M
Subjects: Animals, Disease Models, Animal, GABAergic Neurons drug effects, GABAergic Neurons metabolism, Ketamine pharmacokinetics, Ketamine therapeutic use, Methyl-CpG-Binding Protein 2 genetics, Mice, Mice, Inbred C57BL, Mice, Knockout, Neurons drug effects, Neurons physiology, Parvalbumins metabolism, Phenotype, Photic Stimulation, Pyramidal Cells drug effects, Pyramidal Cells metabolism, Respiration drug effects, Rett Syndrome drug therapy, Survival Analysis, Visual Acuity drug effects, Visual Cortex drug effects, Visual Cortex physiopathology, Ketamine administration & dosage, Receptors, N-Methyl-D-Aspartate antagonists & inhibitors, Rett Syndrome physiopathology
Abstract: Background: Rett syndrome (RTT) is a neurological disorder caused by mutation of the X-linked MECP2 gene, which results in the progressive disruption of excitatory and inhibitory neuronal circuits. To date, there is no effective treatment available for the disorder. Studies conducted in RTT patients and murine models have shown altered expression of N-methyl-D-aspartate receptors (NMDARs). Genetic deletion of the NMDAR subunit, GluN2A, in mice lacking Mecp2 is sufficient to prevent RTT phenotypes, including regression of vision., Methods: We performed a systematic, randomized preclinical trial of chronic administration of low-dose (8 mg/kg, intraperitoneal) ketamine, an NMDAR antagonist, starting either early in development or at the onset of RTT phenotype in Mecp2-null mice., Results: Daily exposure to ketamine ameliorated RTT symptoms and extended the life span of treated Mecp2-null mice without adverse side effects. Furthermore, significant improvement was observed in cortical processing and connectivity, which were fully restored to a wild-type level, particularly when treatment was started at the onset of regression., Conclusions: Our findings provide strong evidence that targeting NMDA receptors can be a safe and effective treatment for RTT., (Copyright © 2016. Published by Elsevier Inc.)
Published: 2016
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38. Cell-Specific Regulation of N-Methyl-D-Aspartate Receptor Maturation by Mecp2 in Cortical Circuits.

Author: Mierau SB, Patrizi A, Hensch TK, and Fagiolini M
Subjects: Animals, Female, Interneurons cytology, Interneurons metabolism, Male, Membrane Potentials, Methyl-CpG-Binding Protein 2 genetics, Mice, Mice, Inbred C57BL, Mice, Knockout, Parvalbumins metabolism, Protein Subunits metabolism, Protein Subunits physiology, Pyramidal Cells cytology, Pyramidal Cells metabolism, Receptors, N-Methyl-D-Aspartate metabolism, Synapses metabolism, Synapses physiology, Visual Cortex cytology, Visual Cortex metabolism, Interneurons physiology, Methyl-CpG-Binding Protein 2 physiology, Pyramidal Cells physiology, Receptors, N-Methyl-D-Aspartate physiology, Visual Cortex physiology
Abstract: Background: Early postnatal experience shapes N-methyl-D-aspartate receptor (NMDAR) subunit composition and kinetics at excitatory synapses onto pyramidal cells; however, little is known about NMDAR maturation onto inhibitory interneurons., Methods: We combined whole-cell patch clamp recordings (n = 440) of NMDAR-mediated currents from layer-4-to-layer-2/3 synapses onto pyramidal and green fluorescent protein labeled parvalbumin-positive (PV) interneurons in visual cortex at three developmental ages (15, 30, and 45 postnatal days) with array tomography three-dimensional reconstructions of NMDAR subunits GluN2A- and GluN2B-positive synapses onto PV cells., Results: We show that the trajectory of the NMDAR subunit switch is slower in PV interneurons than in excitatory pyramidal cells in visual cortex. Notably, this differential time course is reversed in the absence of methyl-CpG-binding protein, MECP2, the molecular basis for cognitive decline in Rett syndrome and some cases of autism. Additional genetic reduction of GluN2A subunits, which prevents regression of vision in Mecp2-knockout mice, specifically rescues the accelerated NMDAR maturation in PV cells., Conclusions: We demonstrate 1) the time course of NMDAR maturation is cell-type specific, and 2) a new cell-type specific role for Mecp2 in the development of NMDAR subunit composition. Reducing GluN2A expression in Mecp2-knockout mice, which prevents the decline in visual cortical function, also prevents the premature NMDAR maturation in PV cells. Thus, circuit-based therapies targeting NMDAR subunit composition on PV cells may provide novel treatments for Rett syndrome., (Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)
Published: 2016
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39. Sensory experience regulates cortical inhibition by inducing IGF1 in VIP neurons.

Author: Mardinly AR, Spiegel I, Patrizi A, Centofante E, Bazinet JE, Tzeng CP, Mandel-Brehm C, Harmin DA, Adesnik H, Fagiolini M, and Greenberg ME
Subjects: Animals, Female, Male, Mice, Mice, Inbred C57BL, Neural Pathways, Neuronal Plasticity, Neurons cytology, Pyramidal Cells metabolism, Synapses metabolism, Vision, Ocular physiology, Insulin-Like Growth Factor I metabolism, Neural Inhibition, Neurons metabolism, Vasoactive Intestinal Peptide metabolism, Visual Cortex cytology, Visual Cortex physiology
Abstract: Inhibitory neurons regulate the adaptation of neural circuits to sensory experience, but the molecular mechanisms by which experience controls the connectivity between different types of inhibitory neuron to regulate cortical plasticity are largely unknown. Here we show that exposure of dark-housed mice to light induces a gene program in cortical vasoactive intestinal peptide (VIP)-expressing neurons that is markedly distinct from that induced in excitatory neurons and other subtypes of inhibitory neuron. We identify Igf1 as one of several activity-regulated genes that are specific to VIP neurons, and demonstrate that IGF1 functions cell-autonomously in VIP neurons to increase inhibitory synaptic input onto these neurons. Our findings further suggest that in cortical VIP neurons, experience-dependent gene transcription regulates visual acuity by activating the expression of IGF1, thus promoting the inhibition of disinhibitory neurons and affecting inhibition onto cortical pyramidal neurons.
Published: 2016
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40. MPX-004 and MPX-007: New Pharmacological Tools to Study the Physiology of NMDA Receptors Containing the GluN2A Subunit.

Author: Volkmann RA, Fanger CM, Anderson DR, Sirivolu VR, Paschetto K, Gordon E, Virginio C, Gleyzes M, Buisson B, Steidl E, Mierau SB, Fagiolini M, and Menniti FS
Subjects: Animals, CA1 Region, Hippocampal cytology, Calcium metabolism, Cells, Cultured, Dogs, Excitatory Postsynaptic Potentials drug effects, Female, Glutamic Acid metabolism, Glycine metabolism, Humans, Ion Channel Gating drug effects, Madin Darby Canine Kidney Cells, Male, Neurons drug effects, Neurons metabolism, Oocytes metabolism, Pyrazines chemistry, Rats, Sprague-Dawley, Receptors, AMPA metabolism, Receptors, N-Methyl-D-Aspartate antagonists & inhibitors, Structure-Activity Relationship, Sulfonamides chemistry, Xenopus, Protein Subunits metabolism, Pyrazines pharmacology, Receptors, N-Methyl-D-Aspartate metabolism, Sulfonamides pharmacology
Abstract: GluN2A is the most abundant of the GluN2 NMDA receptor subunits in the mammalian CNS. Physiological and genetic evidence implicate GluN2A-containing receptors in susceptibility to autism, schizophrenia, childhood epilepsy and neurodevelopmental disorders such as Rett Syndrome. However, GluN2A-selective pharmacological probes to explore the therapeutic potential of targeting these receptors have been lacking. Here we disclose a novel series of pyrazine-containing GluN2A antagonists exemplified by MPX-004 (5-(((3-chloro-4-fluorophenyl)sulfonamido)methyl)-N-((2-methylthiazol-5-yl)methyl)pyrazine-2-carboxamide) and MPX-007 (5-(((3-fluoro-4-fluorophenyl)sulfonamido)methyl)-N-((2-methylthiazol-5-yl)methyl)methylpyrazine-2-carboxamide). MPX-004 and MPX-007 inhibit GluN2A-containing NMDA receptors expressed in HEK cells with IC50s of 79 nM and 27 nM, respectively. In contrast, at concentrations that completely inhibited GluN2A activity these compounds have no inhibitory effect on GluN2B or GluN2D receptor-mediated responses in similar HEK cell-based assays. Potency and selectivity were confirmed in electrophysiology assays in Xenopus oocytes expressing GluN2A-D receptor subtypes. Maximal concentrations of MPX-004 and MPX-007 inhibited ~30% of the whole-cell current in rat pyramidal neurons in primary culture and MPX-004 inhibited ~60% of the total NMDA receptor-mediated EPSP in rat hippocampal slices. GluN2A-selectivity at native receptors was confirmed by the finding that MPX-004 had no inhibitory effect on NMDA receptor mediated synaptic currents in cortical slices from GRIN2A knock out mice. Thus, MPX-004 and MPX-007 offer highly selective pharmacological tools to probe GluN2A physiology and involvement in neuropsychiatric and developmental disorders.
Published: 2016
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41. Restoration of Visual Function by Enhancing Conduction in Regenerated Axons.

Author: Bei F, Lee HHC, Liu X, Gunner G, Jin H, Ma L, Wang C, Hou L, Hensch TK, Frank E, Sanes JR, Chen C, Fagiolini M, and He Z
Subjects: 4-Aminopyridine pharmacology, Animals, Axons drug effects, Ciliary Neurotrophic Factor metabolism, Electrophysiological Phenomena, Eye metabolism, Insulin-Like Growth Factor I metabolism, Mice, Myelin Sheath metabolism, Optic Nerve, Osteopontin metabolism, PTEN Phosphohydrolase metabolism, Potassium Channel Blockers pharmacology, Regeneration drug effects, Suppressor of Cytokine Signaling 3 Protein, Suppressor of Cytokine Signaling Proteins metabolism, Synapses, Axons physiology, Superior Colliculi physiology
Abstract: Although a number of repair strategies have been shown to promote axon outgrowth following neuronal injury in the mammalian CNS, it remains unclear whether regenerated axons establish functional synapses and support behavior. Here, in both juvenile and adult mice, we show that either PTEN and SOCS3 co-deletion, or co-overexpression of osteopontin (OPN)/insulin-like growth factor 1 (IGF1)/ciliary neurotrophic factor (CNTF), induces regrowth of retinal axons and formation of functional synapses in the superior colliculus (SC) but not significant recovery of visual function. Further analyses suggest that regenerated axons fail to conduct action potentials from the eye to the SC due to lack of myelination. Consistent with this idea, administration of voltage-gated potassium channel blockers restores conduction and results in increased visual acuity. Thus, enhancing both regeneration and conduction effectively improves function after retinal axon injury., (Copyright © 2016 Elsevier Inc. All rights reserved.)
Published: 2016
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42. Remodeling of retrotransposon elements during epigenetic induction of adult visual cortical plasticity by HDAC inhibitors.

Author: Lennartsson A, Arner E, Fagiolini M, Saxena A, Andersson R, Takahashi H, Noro Y, Sng J, Sandelin A, Hensch TK, and Carninci P
Abstract: Background: The capacity for plasticity in the adult brain is limited by the anatomical traces laid down during early postnatal life. Removing certain molecular brakes, such as histone deacetylases (HDACs), has proven to be effective in recapitulating juvenile plasticity in the mature visual cortex (V1). We investigated the chromatin structure and transcriptional control by genome-wide sequencing of DNase I hypersensitive sites (DHSS) and cap analysis of gene expression (CAGE) libraries after HDAC inhibition by valproic acid (VPA) in adult V1., Results: We found that VPA reliably reactivates the critical period plasticity and induces a dramatic change of chromatin organization in V1 yielding significantly greater accessibility distant from promoters, including at enhancer regions. VPA also induces nucleosome eviction specifically from retrotransposon (in particular SINE) elements. The transiently accessible SINE elements overlap with transcription factor-binding sites of the Fox family. Mapping of transcription start site activity using CAGE revealed transcription of epigenetic and neural plasticity-regulating genes following VPA treatment, which may help to re-program the genomic landscape and reactivate plasticity in the adult cortex., Conclusions: Treatment with HDAC inhibitors increases accessibility to enhancers and repetitive elements underlying brain-specific gene expression and reactivation of visual cortical plasticity.
Published: 2015
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43. Visual evoked potentials detect cortical processing deficits in Rett syndrome.

Author: LeBlanc JJ, DeGregorio G, Centofante E, Vogel-Farley VK, Barnes K, Kaufmann WE, Fagiolini M, and Nelson CA
Subjects: Aging physiology, Animals, Biomarkers, Child, Child, Preschool, Disease Progression, Electroencephalography, Female, Humans, Infant, Methyl-CpG-Binding Protein 2 genetics, Mice, Mice, Inbred C57BL, Mutation genetics, Photic Stimulation, Visual Acuity, Evoked Potentials, Visual physiology, Rett Syndrome physiopathology, Visual Cortex physiopathology
Abstract: Objective: Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutation of the X-linked MECP2 gene and characterized by developmental regression during the first few years of life. The objective of this study was to investigate if the visual evoked potential (VEP) could be used as an unbiased, quantitative biomarker to monitor brain function in RTT., Methods: We recorded pattern-reversal VEPs in Mecp2 heterozygous female mice and 34 girls with RTT. The amplitudes and latencies of VEP waveform components were quantified, and were related to disease stage, clinical severity, and MECP2 mutation type in patients. Visual acuity was also assessed in both mice and patients by modulating the spatial frequency of the stimuli., Results: Mecp2 heterozygous female mice and RTT patients exhibited a similar decrease in VEP amplitude that was most striking in the later stages of the disorder. RTT patients also displayed a slower recovery from the principal peak of the VEP response that was impacted by MECP2 mutation type. When the spatial frequency of the stimulus was increased, both patients and mice displayed a deficit in discriminating smaller patterns, indicating lower visual spatial acuity in RTT., Interpretation: VEP is a method that can be used to assess brain function across species and in children with severe disabilities like RTT. Our findings support the introduction of standardized VEP analysis in clinical and research settings to probe the neurobiological mechanism underlying functional impairment and to longitudinally monitor progression of the disorder and response to treatment., (© 2015 American Neurological Association.)
Published: 2015
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44. Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells.

Author: Arner E, Daub CO, Vitting-Seerup K, Andersson R, Lilje B, Drabløs F, Lennartsson A, Rönnerblad M, Hrydziuszko O, Vitezic M, Freeman TC, Alhendi AM, Arner P, Axton R, Baillie JK, Beckhouse A, Bodega B, Briggs J, Brombacher F, Davis M, Detmar M, Ehrlund A, Endoh M, Eslami A, Fagiolini M, Fairbairn L, Faulkner GJ, Ferrai C, Fisher ME, Forrester L, Goldowitz D, Guler R, Ha T, Hara M, Herlyn M, Ikawa T, Kai C, Kawamoto H, Khachigian LM, Klinken SP, Kojima S, Koseki H, Klein S, Mejhert N, Miyaguchi K, Mizuno Y, Morimoto M, Morris KJ, Mummery C, Nakachi Y, Ogishima S, Okada-Hatakeyama M, Okazaki Y, Orlando V, Ovchinnikov D, Passier R, Patrikakis M, Pombo A, Qin XY, Roy S, Sato H, Savvi S, Saxena A, Schwegmann A, Sugiyama D, Swoboda R, Tanaka H, Tomoiu A, Winteringham LN, Wolvetang E, Yanagi-Mizuochi C, Yoneda M, Zabierowski S, Zhang P, Abugessaisa I, Bertin N, Diehl AD, Fukuda S, Furuno M, Harshbarger J, Hasegawa A, Hori F, Ishikawa-Kato S, Ishizu Y, Itoh M, Kawashima T, Kojima M, Kondo N, Lizio M, Meehan TF, Mungall CJ, Murata M, Nishiyori-Sueki H, Sahin S, Nagao-Sato S, Severin J, de Hoon MJ, Kawai J, Kasukawa T, Lassmann T, Suzuki H, Kawaji H, Summers KM, Wells C, Hume DA, Forrest AR, Sandelin A, Carninci P, and Hayashizaki Y
Subjects: Animals, Binding Sites, Cattle, Dogs, Mice, RNA, Messenger genetics, RNA, Messenger metabolism, Rats, Stem Cells metabolism, Cell Differentiation genetics, Enhancer Elements, Genetic, Gene Expression Regulation, Developmental, Stem Cells cytology, Transcription Factors metabolism, Transcription, Genetic
Abstract: Although it is generally accepted that cellular differentiation requires changes to transcriptional networks, dynamic regulation of promoters and enhancers at specific sets of genes has not been previously studied en masse. Exploiting the fact that active promoters and enhancers are transcribed, we simultaneously measured their activity in 19 human and 14 mouse time courses covering a wide range of cell types and biological stimuli. Enhancer RNAs, then messenger RNAs encoding transcription factors, dominated the earliest responses. Binding sites for key lineage transcription factors were simultaneously overrepresented in enhancers and promoters active in each cellular system. Our data support a highly generalizable model in which enhancer transcription is the earliest event in successive waves of transcriptional change during cellular differentiation or activation., (Copyright © 2015, American Association for the Advancement of Science.)
Published: 2015
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45. CAGE-defined promoter regions of the genes implicated in Rett Syndrome.

Author: Vitezic M, Bertin N, Andersson R, Lipovich L, Kawaji H, Lassmann T, Sandelin A, Heutink P, Goldowitz D, Ha T, Zhang P, Patrizi A, Fagiolini M, Forrest AR, Carninci P, and Saxena A
Subjects: Animals, Brain metabolism, Brain pathology, Cell Line, Tumor, CpG Islands genetics, Forkhead Transcription Factors genetics, Genomics, Histones genetics, Humans, Methyl-CpG-Binding Protein 2 genetics, Mice, Nerve Tissue Proteins genetics, Neurons metabolism, Protein Serine-Threonine Kinases genetics, Rett Syndrome pathology, TATA Box genetics, Transcription Initiation Site, Gene Expression Profiling, Promoter Regions, Genetic genetics, Rett Syndrome genetics
Abstract: Background: Mutations in three functionally diverse genes cause Rett Syndrome. Although the functions of Forkhead box G1 (FOXG1), Methyl CpG binding protein 2 (MECP2) and Cyclin-dependent kinase-like 5 (CDKL5) have been studied individually, not much is known about their relation to each other with respect to expression levels and regulatory regions. Here we analyzed data from hundreds of mouse and human samples included in the FANTOM5 project, to identify transcript initiation sites, expression levels, expression correlations and regulatory regions of the three genes., Results: Our investigations reveal the predominantly used transcription start sites (TSSs) for each gene including novel transcription start sites for FOXG1. We show that FOXG1 expression is poorly correlated with the expression of MECP2 and CDKL5. We identify promoter shapes for each TSS, the predicted location of enhancers for each gene and the common transcription factors likely to regulate the three genes. Our data imply Polycomb Repressive Complex 2 (PRC2) mediated silencing of Foxg1 in cerebellum., Conclusions: Our analyses provide a comprehensive picture of the regulatory regions of the three genes involved in Rett Syndrome.
Published: 2014
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46. Sensory integration in mouse insular cortex reflects GABA circuit maturation.

Author: Gogolla N, Takesian AE, Feng G, Fagiolini M, and Hensch TK
Subjects: Animals, Autistic Disorder genetics, Cerebral Cortex drug effects, Cerebral Cortex growth & development, Diazepam pharmacology, Disease Models, Animal, GABAergic Neurons drug effects, Glutamate Decarboxylase genetics, Glutamate Decarboxylase physiology, Male, Methyl-CpG-Binding Protein 2 genetics, Methyl-CpG-Binding Protein 2 physiology, Mice, Mice, Knockout, Microfilament Proteins, Nerve Tissue Proteins genetics, Nerve Tissue Proteins physiology, Neural Pathways drug effects, Neural Pathways physiology, Sensation drug effects, Sensation genetics, Species Specificity, Cerebral Cortex physiology, GABAergic Neurons physiology, Neural Pathways growth & development, Sensation physiology
Abstract: Insular cortex (IC) contributes to a variety of complex brain functions, such as communication, social behavior, and self-awareness through the integration of sensory, emotional, and cognitive content. How the IC acquires its integrative properties remains unexplored. We compared the emergence of multisensory integration (MSI) in the IC of behaviorally distinct mouse strains. While adult C57BL/6 mice exhibited robust MSI, this capacity was impaired in the inbred BTBR T+tf/J mouse model of idiopathic autism. The deficit reflected weakened γ-aminobutyric acid (GABA) circuits and compromised postnatal pruning of cross-modal input. Transient pharmacological enhancement by diazepam in BTBR mice during an early sensitive period rescued inhibition and integration in the adult IC. Moreover, impaired MSI was common across three other monogenic models (GAD65, Shank3, and Mecp2 knockout mice) displaying behavioral phenotypes and parvalbumin-circuit abnormalities. Our findings offer developmental insight into a key neural circuit relevant to neuropsychiatric conditions like schizophrenia and autism., (Copyright © 2014 Elsevier Inc. All rights reserved.)
Published: 2014
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47. A promoter-level mammalian expression atlas.

Author: Forrest AR, Kawaji H, Rehli M, Baillie JK, de Hoon MJ, Haberle V, Lassmann T, Kulakovskiy IV, Lizio M, Itoh M, Andersson R, Mungall CJ, Meehan TF, Schmeier S, Bertin N, Jørgensen M, Dimont E, Arner E, Schmidl C, Schaefer U, Medvedeva YA, Plessy C, Vitezic M, Severin J, Semple C, Ishizu Y, Young RS, Francescatto M, Alam I, Albanese D, Altschuler GM, Arakawa T, Archer JA, Arner P, Babina M, Rennie S, Balwierz PJ, Beckhouse AG, Pradhan-Bhatt S, Blake JA, Blumenthal A, Bodega B, Bonetti A, Briggs J, Brombacher F, Burroughs AM, Califano A, Cannistraci CV, Carbajo D, Chen Y, Chierici M, Ciani Y, Clevers HC, Dalla E, Davis CA, Detmar M, Diehl AD, Dohi T, Drabløs F, Edge AS, Edinger M, Ekwall K, Endoh M, Enomoto H, Fagiolini M, Fairbairn L, Fang H, Farach-Carson MC, Faulkner GJ, Favorov AV, Fisher ME, Frith MC, Fujita R, Fukuda S, Furlanello C, Furino M, Furusawa J, Geijtenbeek TB, Gibson AP, Gingeras T, Goldowitz D, Gough J, Guhl S, Guler R, Gustincich S, Ha TJ, Hamaguchi M, Hara M, Harbers M, Harshbarger J, Hasegawa A, Hasegawa Y, Hashimoto T, Herlyn M, Hitchens KJ, Ho Sui SJ, Hofmann OM, Hoof I, Hori F, Huminiecki L, Iida K, Ikawa T, Jankovic BR, Jia H, Joshi A, Jurman G, Kaczkowski B, Kai C, Kaida K, Kaiho A, Kajiyama K, Kanamori-Katayama M, Kasianov AS, Kasukawa T, Katayama S, Kato S, Kawaguchi S, Kawamoto H, Kawamura YI, Kawashima T, Kempfle JS, Kenna TJ, Kere J, Khachigian LM, Kitamura T, Klinken SP, Knox AJ, Kojima M, Kojima S, Kondo N, Koseki H, Koyasu S, Krampitz S, Kubosaki A, Kwon AT, Laros JF, Lee W, Lennartsson A, Li K, Lilje B, Lipovich L, Mackay-Sim A, Manabe R, Mar JC, Marchand B, Mathelier A, Mejhert N, Meynert A, Mizuno Y, de Lima Morais DA, Morikawa H, Morimoto M, Moro K, Motakis E, Motohashi H, Mummery CL, Murata M, Nagao-Sato S, Nakachi Y, Nakahara F, Nakamura T, Nakamura Y, Nakazato K, van Nimwegen E, Ninomiya N, Nishiyori H, Noma S, Noma S, Noazaki T, Ogishima S, Ohkura N, Ohimiya H, Ohno H, Ohshima M, Okada-Hatakeyama M, Okazaki Y, Orlando V, Ovchinnikov DA, Pain A, Passier R, Patrikakis M, Persson H, Piazza S, Prendergast JG, Rackham OJ, Ramilowski JA, Rashid M, Ravasi T, Rizzu P, Roncador M, Roy S, Rye MB, Saijyo E, Sajantila A, Saka A, Sakaguchi S, Sakai M, Sato H, Savvi S, Saxena A, Schneider C, Schultes EA, Schulze-Tanzil GG, Schwegmann A, Sengstag T, Sheng G, Shimoji H, Shimoni Y, Shin JW, Simon C, Sugiyama D, Sugiyama T, Suzuki M, Suzuki N, Swoboda RK, 't Hoen PA, Tagami M, Takahashi N, Takai J, Tanaka H, Tatsukawa H, Tatum Z, Thompson M, Toyodo H, Toyoda T, Valen E, van de Wetering M, van den Berg LM, Verado R, Vijayan D, Vorontsov IE, Wasserman WW, Watanabe S, Wells CA, Winteringham LN, Wolvetang E, Wood EJ, Yamaguchi Y, Yamamoto M, Yoneda M, Yonekura Y, Yoshida S, Zabierowski SE, Zhang PG, Zhao X, Zucchelli S, Summers KM, Suzuki H, Daub CO, Kawai J, Heutink P, Hide W, Freeman TC, Lenhard B, Bajic VB, Taylor MS, Makeev VJ, Sandelin A, Hume DA, Carninci P, and Hayashizaki Y
Subjects: Animals, Cell Line, Cells, Cultured, Cluster Analysis, Conserved Sequence genetics, Gene Expression Regulation genetics, Gene Regulatory Networks genetics, Genes, Essential genetics, Genome genetics, Humans, Mice, Open Reading Frames genetics, Organ Specificity, RNA, Messenger analysis, RNA, Messenger genetics, Transcription Factors metabolism, Transcription Initiation Site, Transcription, Genetic genetics, Atlases as Topic, Molecular Sequence Annotation, Promoter Regions, Genetic genetics, Transcriptome genetics
Abstract: Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly 'housekeeping', whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.
Published: 2014
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48. Aberrant development and plasticity of excitatory visual cortical networks in the absence of cpg15.

Author: Picard N, Leslie JH, Trowbridge SK, Subramanian J, Nedivi E, and Fagiolini M
Subjects: Animals, Excitatory Postsynaptic Potentials physiology, Female, GPI-Linked Proteins deficiency, Male, Mice, Mice, Knockout, Nerve Net growth & development, Visual Cortex growth & development, Visual Pathways growth & development, Nerve Net metabolism, Nerve Tissue Proteins deficiency, Neuronal Plasticity physiology, Visual Cortex metabolism, Visual Pathways metabolism
Abstract: During development, experience plays a crucial role in sculpting neuronal connections. Patterned neural activity guides formation of functional neural circuits through the selective stabilization of some synapses and the pruning of others. Activity-regulated factors are fundamental to this process, but their roles in synapse stabilization and maturation is still poorly understood. CPG15, encoded by the activity-regulated gene candidate plasticity gene 15, is a small, glycosylphosphatidylinositol (GPI)-linked, extracellular protein that promotes synapse stabilization. Here we show that global knock-out of cpg15 results in abnormal postnatal development of the excitatory network in visual cortex and an associated disruption in development of visual receptive field properties. In addition, whereas repeated stimulation induced potentiation and depression in wild-type mice, the depression was slower in cpg15 knock-out mice, suggesting impairment in short-term depression-like mechanisms. These findings establish the requirement for cpg15 in activity-dependent development of the visual system and demonstrate the importance of timely excitatory network development for normal visual function.
Published: 2014
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49. Visual acuity development and plasticity in the absence of sensory experience.

Author: Kang E, Durand S, LeBlanc JJ, Hensch TK, Chen C, and Fagiolini M
Subjects: Animals, Male, Mice, Mice, Inbred C57BL, Visual Cortex growth & development, Neuronal Plasticity physiology, Neurons physiology, Sensory Deprivation physiology, Vision, Monocular physiology, Visual Acuity physiology, Visual Cortex physiology
Abstract: Visual circuits mature and are refined by sensory experience. However, significant gaps remain in our understanding how deprivation influences the development of visual acuity in mice. Here, we perform a longitudinal study assessing the effects of chronic deprivation on the development of the mouse subcortical and cortical visual circuits using a combination of behavioral optomotor testing, in vivo visual evoked responses (VEP) and single-unit cortical recordings. As previously reported, orientation tuning was degraded and onset of ocular dominance plasticity was delayed and remained open in chronically deprived mice. Surprisingly, we found that the development of optomotor threshold and VEP acuity can occur in an experience-independent manner, although at a significantly slower rate. Moreover, monocular deprivation elicited amblyopia only during a discrete period of development in the dark. The rate of recovery of optomotor threshold upon exposure of deprived mice to light confirmed a maturational transition regardless of visual input. Together our results revealed a dissociable developmental trajectory for visual receptive-field properties in dark-reared mice suggesting a differential role for spontaneous activity within thalamocortical and intracortical circuits.
Published: 2013
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50. NMDA receptor regulation prevents regression of visual cortical function in the absence of Mecp2.

Author: Durand S, Patrizi A, Quast KB, Hachigian L, Pavlyuk R, Saxena A, Carninci P, Hensch TK, and Fagiolini M
Subjects: Animals, Disease Models, Animal, Female, Male, Methyl-CpG-Binding Protein 2 genetics, Mice, Mice, Knockout, Nerve Degeneration pathology, Nerve Degeneration physiopathology, Neurons metabolism, Parvalbumins metabolism, Receptors, N-Methyl-D-Aspartate genetics, Rett Syndrome pathology, Vision Tests, Visual Cortex pathology, Visual Cortex physiopathology, Visual Pathways pathology, Visual Pathways physiology, Visual Pathways physiopathology, Methyl-CpG-Binding Protein 2 physiology, Receptors, N-Methyl-D-Aspartate physiology, Rett Syndrome physiopathology, Visual Acuity physiology, Visual Cortex physiology
Abstract: Brain function is shaped by postnatal experience and vulnerable to disruption of Methyl-CpG-binding protein, Mecp2, in multiple neurodevelopmental disorders. How Mecp2 contributes to the experience-dependent refinement of specific cortical circuits and their impairment remains unknown. We analyzed vision in gene-targeted mice and observed an initial normal development in the absence of Mecp2. Visual acuity then rapidly regressed after postnatal day P35-40 and cortical circuits largely fell silent by P55-60. Enhanced inhibitory gating and an excess of parvalbumin-positive, perisomatic input preceded the loss of vision. Both cortical function and inhibitory hyperconnectivity were strikingly rescued independent of Mecp2 by early sensory deprivation or genetic deletion of the excitatory NMDA receptor subunit, NR2A. Thus, vision is a sensitive biomarker of progressive cortical dysfunction and may guide novel, circuit-based therapies for Mecp2 deficiency., (Copyright © 2012 Elsevier Inc. All rights reserved.)
Published: 2012
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