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Larimore, J.; Ryder, P.V.; Kim, K.-Y.; Ambrose, L.A.; Chapleau, C.; Calfa, G.; Gross, C.; Bassell, G.J.; Pozzo-Miller, L.; Smith, Y.; Talbot, K.; Park, I.-H.; Faundez, V. |
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Title |
MeCP2 regulates the synaptic expression of a Dysbindin-BLOC-1 network component in mouse brain and human induced pluripotent stem cell-derived neurons |
Type |
Journal Article |
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Year |
2013 |
Publication |
PloS one |
Abbreviated Journal |
PLoS One |
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Volume |
8 |
Issue |
6 |
Pages  |
e65069 |
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Keywords |
Animals; Carrier Proteins/genetics/*metabolism; Computational Biology; Dystrophin-Associated Proteins; *Gene Expression Regulation; Hippocampus/*cytology; Humans; Induced Pluripotent Stem Cells/cytology; Lectins/genetics/*metabolism; Methyl-CpG-Binding Protein 2/deficiency/*metabolism; Mice; Neurons/cytology/*metabolism; Protein Interaction Maps; RNA, Messenger/genetics/metabolism; Synapses/*metabolism |
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Abstract |
Clinical, epidemiological, and genetic evidence suggest overlapping pathogenic mechanisms between autism spectrum disorder (ASD) and schizophrenia. We tested this hypothesis by asking if mutations in the ASD gene MECP2 which cause Rett syndrome affect the expression of genes encoding the schizophrenia risk factor dysbindin, a subunit of the biogenesis of lysosome-related organelles complex-1 (BLOC-1), and associated interacting proteins. We measured mRNA and protein levels of key components of a dysbindin interaction network by, quantitative real time PCR and quantitative immunohistochemistry in hippocampal samples of wild-type and Mecp2 mutant mice. In addition, we confirmed results by performing immunohistochemistry of normal human hippocampus and quantitative qRT-PCR of human inducible pluripotent stem cells (iPSCs)-derived human neurons from Rett syndrome patients. We defined the distribution of the BLOC-1 subunit pallidin in human and mouse hippocampus and contrasted this distribution with that of symptomatic Mecp2 mutant mice. Neurons from mutant mice and Rett syndrome patients displayed selectively reduced levels of pallidin transcript. Pallidin immunoreactivity decreased in the hippocampus of symptomatic Mecp2 mutant mice, a feature most prominent at asymmetric synapses as determined by immunoelectron microcopy. Pallidin immunoreactivity decreased concomitantly with reduced BDNF content in the hippocampus of Mecp2 mice. Similarly, BDNF content was reduced in the hippocampus of BLOC-1 deficient mice suggesting that genetic defects in BLOC-1 are upstream of the BDNF phenotype in Mecp2 deficient mice. Our results demonstrate that the ASD-related gene Mecp2 regulates the expression of components belonging to the dysbindin interactome and these molecular differences may contribute to synaptic phenotypes that characterize Mecp2 deficiencies and ASD. |
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Department of Biology, Agnes Scott College, Decatur, Georgia, USA |
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PMID:23750231; PMCID:PMC3672180 |
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refbase @ user @ |
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16886 |
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Humpenöder, F.; Popp, A.; Dietrich, J.P.; Klein, D.; Lotze-Campen, H.; Bonsch, M.; Bodirsky, B.L.; Weindl, I.; Stevanovic, M.; Müller, C. |
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Investigating afforestation and bioenergy CCS as climate change mitigation strategies |
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Journal Article |
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Year |
2014 |
Publication |
Environmental Research Letters |
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9 |
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6 |
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064029 |
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CropM; TradeM; tst |
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refbase @ user @ |
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16599 |
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Abbott, B.P.; Abbott, R.; Adhikari, R.; Ajith, P.; Allen, B.; Allen, G.; Amin, R.S.; Anderson, S.B.; Anderson, W.G.; Arain, M.A.; Araya, M.; Armandula, H.; Armor, P.; Aso, Y.; Aston, S.; Aufmuth, P.; Aulbert, C.; Babak, S.; Baker, P.; Ballmer, S.; Barker, C.; Barker, D.; Barr, B.; Barriga, P.; Barsotti, L.; Barton, M.A.; Bartos, I.; Bassiri, R.; Bastarrika, M.; Behnke, B.; Benacquista, M.; Betzwieser, J.; Beyersdorf, P.T.; Bilenko, I.A.; Billingsley, G.; Biswas, R.; Black, E.; Blackburn, J.K.; Blackburn, L.; Blair, D.; Bland, B.; Bodiya, T.P.; Bogue, L.; Bork, R.; Boschi, V.; Bose, S.; Brady, P.R.; Braginsky, V.B.; Brau, J.E.; Bridges, D.O.; Brinkmann, M.; Brooks, A.F.; Brown, D.A.; Brummit, A.; Brunet, G.; Bullington, A.; Buonanno, A.; Burmeister, O.; Byer, R.L.; Cadonati, L.; Camp, J.B.; Cannizzo, J.; Cannon, K.C.; Cao, J.; Cardenas, L.; Caride, S.; Castaldi, G.; Caudill, S.; Cavaglia, M.; Cepeda, C.; Chalermsongsak, T.; Chalkley, E.; Charlton, P.; Chatterji, S.; Chelkowski, S.; Chen, Y.; Christensen, N.; Chung, C.T.Y.; Clark, D.; Clark, J.; Clayton, J.H.; Cokelaer, T.; Colacino, C.N.; Conte, R.; Cook, D.; Corbitt, T.R.C.; Cornish, N.; Coward, D.; Coyne, D.C.; Creighton, J.D.E.; Creighton, T.D.; Cruise, A.M.; Culter, R.M.; Cumming, A.; Cunningham, L.; Danilishin, S.L.; Danzmann, K.; Daudert, B.; Davies, G.; Daw, E.J.; DeBra, D.; Degallaix, J.; Dergachev, V.; Desai, S.; DeSalvo, R.; Dhurandhar, S.; Diaz, M.; Dietz, A.; Donovan, F.; Dooley, K.L.; Doomes, E.E.; Drever, R.W.P.; Dueck, J.; Duke, I.; Dumas, J.C.; Dwyer, J.G.; Echols, C.; Edgar, M.; Effler, A.; Ehrens, P.; Espinoza, E.; Etzel, T.; Evans, M.; Evans, T.; Fairhurst, S.; Faltas, Y.; Fan, Y.; Fazi, D.; Fehrmann, H.; Finn, L.S.; Flasch, K.; Foley, S.; Forrest, C.; Fotopoulos, N.; Franzen, A.; Frede, M.; Frei, M.; Frei, Z.; Freise, A.; Frey, R.; Fricke, T.; Fritschel, P.; Frolov, V.V.; Fyffe, M.; Galdi, V.; Garofoli, J.A.; Gholami, I.; Giaime, J.A.; Giampanis, S.; Giardina, K.D.; Goda, K.; Goetz, E.; Goggin, L.M.; Gonzalez, G.; Gorodetsky, M.L.; Goßler, S.; Gouaty, R.; Grant, A.; Gras, S.; Gray, C.; Gray, M.; Greenhalgh, R.J.S.; Gretarsson, A.M.; Grimaldi, F.; Grosso, R.; Grote, H.; Grunewald, S.; Guenther, M.; Gustafson, E.K.; Gustafson, R.; Hage, B.; Hallam, J.M.; Hammer, D.; Hammond, G.D.; Hanna, C.; Hanson, J.; Harms, J.; Harry, G.M.; Harry, I.W.; Harstad, E.D.; Haughian, K.; Hayama, K.; Heefner, J.; Heng, I.S.; Heptonstall, A.; Hewitson, M.; Hild, S.; Hirose, E.; Hoak, D.; Hodge, K.A.; Holt, K.; Hosken, D.J.; Hough, J.; Hoyland, D.; Hughey, B.; Huttner, S.H.; Ingram, D.R.; Isogai, T.; Ito, M.; Ivanov, A.; Johnson, B.; Johnson, W.W.; Jones, D.I.; Jones, G.; Jones, R.; Ju, L.; Kalmus, P.; Kalogera, V.; Kandhasamy, S.; Kanner, J.; Kasprzyk, D.; Katsavounidis, E.; Kawabe, K.; Kawamura, S.; Kawazoe, F.; Kells, W.; Keppel, D.G.; Khalaidovski, A.; Khalili, F.Y.; Khan, R.; Khazanov, E.; King, P.; Kissel, J.S.; Klimenko, S.; Kokeyama, K.; Kondrashov, V.; Kopparapu, R.; Koranda, S.; Kozak, D.; Krishnan, B.; Kumar, R.; Kwee, P.; Lam, P.K.; Landry, M.; Lantz, B.; Lazzarini, A.; Lei, H.; Lei, M.; Leindecker, N.; Leonor, I.; Li, C.; Lin, H.; Lindquist, P.E.; Littenberg, T.B.; Lockerbie, N.A.; Lodhia, D.; Longo, M.; Lormand, M.; Lu, P.; Lubinski, M.; Lucianetti, A.; Lueck, H.; Machenschalk, B.; MacInnis, M.; Mageswaran, M.; Mailand, K.; Mandel, I.; Mandic, V.; Márka, S.; Márka, Z.; Markosyan, A.; Markowitz, J.; Maros, E.; Martin, I.W.; Martin, R.M.; Marx, J.N.; Mason, K.; Matichard, F.; Matone, L.; Matzner, R.A.; Mavalvala, N.; McCarthy, R.; McClclland, D.E.; McGuire, S.C.; McHugh, M.; McIntyre, G.; McKechan, D.J.A.; McKenzie, K.; Mehmet, M.; Melatos, A.; Melissinos, A.C.; Menéndez, D.F.; Mendell, G.; Mercer, R.A.; Meshkov, S.; Messenger, C.; Meyer, M.S.; Miller, J.; Minelli, J.; Mino, Y.; Mitrofanov, V.P.; Mitselmakher, G.; Mittleman, R.; Miyakawa, O.; Moe, B.; Mohanty, S.D.; Mohapatra, S.R.P.; Moreno, G.; Morioka, T.; Mors, K.; Mossavi, K.; MowLowry, C.; Mueller, G.; Müller-Ebhardt, H.; Muhammad, D.; Mukherjee, S.; Mukhopadhyay, H.; Mullavey, A.; Munch, J.; Murray, P.G.; Myers, E.; Myers, J.; Nash, T.; Nelson, J.; Newton, G.; Nishizawa, A.; Numata, K.; ODell, J.; OReilly, B.; OShaughnessy, R.; Ochsner, E.; Ogin, G.H.; Ottaway, D.J.; Ottens, R.S.; Overmier, H.; Owen, B.J.; Pan, Y.; Pankow, C.; Papa, M.A.; Parameshwaraiah, V.; Patel, P.; Pedraza, M.; Penn, S.; Perreca, A.; Pierro, V.; Pinto, I.M.; Pitkin, M.; Pletsch, H.J.; Plissi, M.V.; Postiglione, F.; Principe, M.; Prix, R.; Prokhorov, L.; Punken, O.; Quetschke, V.; Raab, F.J.; Rabeling, D.S.; Radkins, H.; Raffai, P.; Raics, Z.; Rainer, N.; Rakhmanov, M.; Raymond, V.; Reed, C.M.; Reed, T.; Rehbein, H.; Reid, S.; Reitze, D.H.; Riesen, R.; Riles, K.; Rivera, B.; Roberts, P.; Robertson, N.A.; Robinson, C.; Robinson, E.L.; Roddy, S.; Röver, C.; Rollins, J.; Romano, J.D.; Romie, J.H.; Rowan, S.; Rüdiger, A.; Russell, P.; Ryan, K.; Sakata, S.; de la Jordana, L.S.; Sandberg, V.; Sannibale, V.; Santamaría, L.; Saraf, S.; Sarin, P.; Sathyaprakash, B.S.; Sato, S.; Satterthwaite, M.; Saulson, P.R.; Savage, R.; Savov, P.; Scanlan, M.; Schilling, R.; Schnabel, R.; Schofield, R.; Schulz, B.; Schutz, B.F.; Schwinberg, P.; Scott, J.; Scott, S.M.; Searle, A.C.; Sears, B.; Seifert, F.; Sellers, D.; Sengupta, A.S.; Sergeev, A.; Shapiro, B.; Shawhan, P.; Shoemaker, D.H.; Sibley, A.; Siemens, X.; Sigg, D.; Sinha, S.; Sintes, A.M.; Slagmolen, B.J.J.; Slutsky, J.; Smith, J.R.; Smith, M.R.; Smith, N.D.; Somiya, K.; Sorazu, B.; Stein, A.; Stein, L.C.; Steplewski, S.; Stochino, A.; Stone, R.; Strain, K.A.; Strigin, S.; Stroeer, A.; Stuver, A.L.; Summerscales, T.Z.; Sun, K.X.; Sung, M.; Sutton, P.J.; Szokoly, G.P.; Talukder, D.; Tang, L.; Tanner, D.B.; Tarabrin, S.P.; Taylor, J.R.; Taylor, R.; Thacker, J.; Thorne, K.A.; Thorne, K.S.; Thüring, A.; Tokmakov, K.V.; Torres, C.; Torrie, C.; Traylor, G.; Trias, M.; Ugolini, D.; Ulmen, J.; Urbanek, K.; Vahlbruch, H.; Vallisneri, M.; Van den Broeck, C.; van der Sluys, M.V.; van Veggel, A.A.; Vass, S.; Vaulin, R.; Vecchio, A.; Veitch, J.; Veitch, P.; Veltkamp, C.; Villar, A.; Vorvick, C.; Vyachanin, S.P.; Waldman, S.J.; Wallace, L.; Ward, R.L.; Weidner, A.; Weinert, M.; Weinstein, A.J.; Weiss, R.; Wen, L.; Wen, S.; Wette, K.; Whelan, J.T.; Whitcomb, S.E.; Whiting, B.F.; Wilkinson, C.; Willems, P.A.; Williams, H.R.; Williams, L.; Willke, B.; Wilmut, I.; Winkelmann, L.; Winkler, W.; Wipf, C.C.; Wiseman, A.G.; Woan, G.; Wooley, R.; Worden, J.; Wu, W.; Yakushin, I.; Yamamoto, H.; Yan, Z.; Yoshida, S.; Zanolin, M.; Zhang, J.; Zhang, L.; Zhao, C.; Zotov, N.; Zucker, M.E.; zur Mühlen, H.; Zweizig, J.; Collaboration, the L.I.G.O.S. |
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Title |
First LIGO search for gravitational wave bursts from cosmic (super)strings |
Type |
Journal Article |
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Year |
2009 |
Publication |
Physical Review D |
Abbreviated Journal |
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80 |
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6 |
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062002 |
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One Physics Ellipse, College Pk, Md 20740-3844 Usa |
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1550-7998 |
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refbase @ admin @ Abbott2009f |
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12845 |
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Abbott, B.P.; Abbott, R.; Adhikari, R.; Ajith, P.; Allen, B.; Allen, G.; Amin, R.S.; Anderson, S.B.; Anderson, W.G.; Arain, M.A.; Araya, M.; Armandula, H.; Armor, P.; Aso, Y.; Aston, S.; Aufmuth, P.; Aulbert, C.; Babak, S.; Baker, P.; Ballmer, S.; Barker, C.; Barker, D.; Barr, B.; Barriga, P.; Barsotti, L.; Barton, M.A.; Bartos, I.; Bassiri, R.; Bastarrika, M.; Behnke, B.; Benacquista, M.; Betzwieser, J.; Beyersdorf, P.T.; Bilenko, I.A.; Billingsley, G.; Biswas, R.; Black, E.; Blackburn, J.K.; Blackburn, L.; Blair, D.; Bland, B.; Bodiya, T.P.; Bogue, L.; Bork, R.; Boschi, V.; Bose, S.; Brady, P.R.; Braginsky, V.B.; Brau, J.E.; Bridges, D.O.; Brinkmann, M.; Brooks, A.F.; Brown, D.A.; Brummit, A.; Brunet, G.; Bullington, A.; Buonanno, A.; Burmeister, O.; Byer, R.L.; Cadonati, L.; Camp, J.B.; Cannizzo, J.; Cannon, K.C.; Cao, J.; Cardenas, L.; Cardoso, V.; Caride, S.; Castaldi, G.; Caudill, S.; Cavaglia, M.; Cepeda, C.; Chalermsongsak, T.; Chalkley, E.; Charlton, P.; Chatterji, S.; Chelkowski, S.; Chen, Y.; Christensen, N.; Chung, C.T.Y.; Clark, D.; Clark, J.; Clayton, J.H.; Cokelaer, T.; Colacino, C.N.; Conte, R.; Cook, D.; Corbitt, T.R.C.; Cornish, N.; Coward, D.; Coyne, D.C.; Creighton, J.D.E.; Creighton, T.D.; Cruise, A.M.; Culter, R.M.; Cumming, A.; Cunningham, L.; Danilishin, S.L.; Danzmann, K.; Daudert, B.; Davies, G.; Daw, E.J.; DeBra, D.; Degallaix, J.; Dergachev, V.; Desai, S.; DeSalvo, R.; Dhurandhar, S.; Diaz, M.; Dietz, A.; Donovan, F.; Dooley, K.L.; Doomes, E.E.; Drever, R.W.P.; Dueck, J.; Duke, I.; Dumas, J.C.; Dwyer, J.G.; Echols, C.; Edgar, M.; Effler, A.; Ehrens, P.; Espinoza, E.; Etzel, T.; Evans, M.; Evans, T.; Fairhurst, S.; Faltas, Y.; Fan, Y.; Fazi, D.; Fehrmann, H.; Finn, L.S.; Flasch, K.; Foley, S.; Forrest, C.; Fotopoulos, N.; Franzen, A.; Frede, M.; Frei, M.; Frei, Z.; Freise, A.; Frey, R.; Fricke, T.; Fritschel, P.; Frolov, V.V.; Fyffe, M.; Galdi, V.; Garofoli, J.A.; Gholami, I.; Giaime, J.A.; Giampanis, S.; Giardina, K.D.; Goda, K.; Goetz, E.; Goggin, L.M.; Gonzalez, G.; Gorodetsky, M.L.; Goßler, S.; Gouaty, R.; Grant, A.; Gras, S.; Gray, C.; Gray, M.; Greenhalgh, R.J.S.; Gretarsson, A.M.; Grimaldi, F.; Grosso, R.; Grote, H.; Grunewald, S.; Guenther, M.; Gustafson, E.K.; Gustafson, R.; Hage, B.; Hallam, J.M.; Hammer, D.; Hammond, G.D.; Hanna, C.; Hanson, J.; Harms, J.; Harry, G.M.; Harry, I.W.; Harstad, E.D.; Haughian, K.; Hayama, K.; Heefner, J.; Heng, I.S.; Heptonstall, A.; Hewitson, M.; Hild, S.; Hirose, E.; Hoak, D.; Hodge, K.A.; Holt, K.; Hosken, D.J.; Hough, J.; Hoyland, D.; Hughey, B.; Huttner, S.H.; Ingram, D.R.; Isogai, T.; Ito, M.; Ivanov, A.; Johnson, B.; Johnson, W.W.; Jones, D.I.; Jones, G.; Jones, R.; Ju, L.; Kalmus, P.; Kalogera, V.; Kandhasamy, S.; Kanner, J.; Kasprzyk, D.; Katsavounidis, E.; Kawabe, K.; Kawamura, S.; Kawazoe, F.; Kells, W.; Keppel, D.G.; Khalaidovski, A.; Khalili, F.Y.; Khan, R.; Khazanov, E.; King, P.; Kissel, J.S.; Klimenko, S.; Kokeyama, K.; Kondrashov, V.; Kopparapu, R.; Koranda, S.; Kozak, D.; Krishnan, B.; Kumar, R.; Kwee, P.; Lam, P.K.; Landry, M.; Lantz, B.; Lazzarini, A.; Lei, H.; Lei, M.; Leindecker, N.; Leonor, I.; Li, C.; Lin, H.; Lindquist, P.E.; Littenberg, T.B.; Lockerbie, N.A.; Lodhia, D.; Longo, M.; Lormand, M.; Lu, P.; Lubinski, M.; Lucianetti, A.; Lueck, H.; Machenschalk, B.; MacInnis, M.; Mageswaran, M.; Mailand, K.; Mandel, I.; Mandic, V.; Márka, S.; Márka, Z.; Markosyan, A.; Markowitz, J.; Maros, E.; Martin, I.W.; Martin, R.M.; Marx, J.N.; Mason, K.; Matichard, F.; Matone, L.; Matzner, R.A.; Mavalvala, N.; McCarthy, R.; McClelland, D.E.; McGuire, S.C.; McHugh, M.; McIntyre, G.; McKechan, D.J.A.; McKenzie, K.; Mehmet, M.; Melatos, A.; Melissinos, A.C.; Menéndez, D.F.; Mendell, G.; Mercer, R.A.; Meshkov, S.; Messenger, C.; Meyer, M.S.; Miller, J.; Minelli, J.; Mino, Y.; Mitrofanov, V.P.; Mitselmakher, G.; Mittleman, R.; Miyakawa, O.; Moe, B.; Mohanty, S.D.; Mohapatra, S.R.P.; Moreno, G.; Morioka, T.; Mors, K.; Mossavi, K.; MowLowry, C.; Mueller, G.; Müller-Ebhardt, H.; Muhammad, D.; Mukherjee, S.; Mukhopadhyay, H.; Mullavey, A.; Munch, J.; Murray, P.G.; Myers, E.; Myers, J.; Nash, T.; Nelson, J.; Newton, G.; Nishizawa, A.; Numata, K.; ODell, J.; OReilly, B.; OShaughnessy, R.; Ochsner, E.; Ogin, G.H.; Ottaway, D.J.; Ottens, R.S.; Overmier, H.; Owen, B.J.; Pan, Y.; Pankow, C.; Papa, M.A.; Parameshwaraiah, V.; Patel, P.; Pedraza, M.; Penn, S.; Perraca, A.; Pierro, V.; Pinto, I.M.; Pitkin, M.; Pletsch, H.J.; Plissi, M.V.; Postiglione, F.; Principe, M.; Prix, R.; Prokhorov, L.; Punken, O.; Quetschke, V.; Raab, F.J.; Rabeling, D.S.; Radkins, H.; Raffai, P.; Raics, Z.; Rainer, N.; Rakhmanov, M.; Raymond, V.; Reed, C.M.; Reed, T.; Rehbein, H.; Reid, S.; Reitze, D.H.; Riesen, R.; Riles, K.; Rivera, B.; Roberts, P.; Robertson, N.A.; Robinson, C.; Robinson, E.L.; Roddy, S.; Röver, C.; Rollins, J.; Romano, J.D.; Romie, J.H.; Rowan, S.; Rüdiger, A.; Russell, P.; Ryan, K.; Sakata, S.; de la Jordana, L.S.; Sandberg, V.; Sannibale, V.; Santamaría, L.; Saraf, S.; Sarin, P.; Sathyaprakash, B.S.; Sato, S.; Satterthwaite, M.; Saulson, P.R.; Savage, R.; Savov, P.; Scanlan, M.; Schilling, R.; Schnabel, R.; Schofield, R.; Schulz, B.; Schutz, B.F.; Schwinberg, P.; Scott, J.; Scott, S.M.; Searle, A.C.; Sears, B.; Seifert, F.; Sellers, D.; Sengupta, A.S.; Sergeev, A.; Shapiro, B.; Shawhan, P.; Shoemaker, D.H.; Sibley, A.; Siemens, X.; Sigg, D.; Sinha, S.; Sintes, A.M.; Slagmolen, B.J.J.; Slutsky, J.; Smith, J.R.; Smith, M.R.; Smith, N.D.; Somiya, K.; Sorazu, B.; Stein, A.; Stein, L.C.; Steplewski, S.; Stochino, A.; Stone, R.; Strain, K.A.; Strigin, S.; Stroeer, A.; Stuver, A.L.; Summerscales, T.Z.; Sun, K.X.; Sung, M.; Sutton, P.J.; Szokoly, G.P.; Talukder, D.; Tang, L.; Tanner, D.B.; Tarabrin, S.P.; Taylor, J.R.; Taylor, R.; Thacker, J.; Thorne, K.A.; Thorne, K.S.; Thüring, A.; Tokmakov, K.V.; Torres, C.; Torrie, C.; Traylor, G.; Trias, M.; Ugolini, D.; Ulmen, J.; Urbanek, K.; Vahlbruch, H.; Vallisneri, M.; Van den Broeck, C.; van der Sluys, M.V.; van Veggel, A.A.; Vass, S.; Vaulin, R.; Vecchio, A.; Veitch, J.; Veitch, P.; Veltkamp, C.; Villar, A.; Vorvick, C.; Vyachanin, S.P.; Waldman, S.J.; Wallace, L.; Ward, R.L.; Weidner, A.; Weinert, M.; Weinstein, A.J.; Weiss, R.; Wen, L.; Wen, S.; Wette, K.; Whelan, J.T.; Whitcomb, S.E.; Whiting, B.F.; Wilkinson, C.; Willems, P.A.; Williams, H.R.; Williams, L.; Willke, B.; Wilmut, I.; Winkelmann, L.; Winkler, W.; Wipf, C.C.; Wiseman, A.G.; Woan, G.; Wooley, R.; Worden, J.; Wu, W.; Yakushin, I.; Yamamoto, H.; Yan, Z.; Yoshida, S.; Zanolin, M.; Zhang, J.; Zhang, L.; Zhao, C.; Zotov, N.; Zucker, M.E.; zur Mühlen, H.; Zweizig, J.; Collaboration, the L.I.G.O.S. |
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Title |
Search for gravitational wave ringdowns from perturbed black holes in LIGO S4 data |
Type |
Journal Article |
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Year |
2009 |
Publication |
Physical Review D |
Abbreviated Journal |
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80 |
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6 |
Pages |
062001 |
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One Physics Ellipse, College Pk, Md 20740-3844 Usa |
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1550-7998 |
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refbase @ admin @ Abbott2009e |
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12844 |
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Author |
Zeng, L.; Zhang, P.; Shi, L.; Yamamoto, V.; Lu, W.; Wang, K. |
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Functional impacts of NRXN1 knockdown on neurodevelopment in stem cell models |
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Journal Article |
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2013 |
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PloS one |
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PLoS One |
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8 |
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3 |
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e59685 |
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Astrocytes/cytology/metabolism; Cell Adhesion Molecules, Neuronal/*genetics/*metabolism; Cell Differentiation/genetics; DNA Transposable Elements; Developmental Disabilities/genetics/metabolism; Gene Expression Regulation; Gene Knockdown Techniques; Humans; Induced Pluripotent Stem Cells/cytology/metabolism; Nerve Tissue Proteins/*genetics/*metabolism; Neural Stem Cells/cytology/metabolism; Neurons/cytology/metabolism; Protein Interaction Maps; Signal Transduction; Stem Cells/*cytology/*metabolism |
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Abstract |
Exonic deletions in NRXN1 have been associated with several neurodevelopmental disorders, including autism, schizophrenia and developmental delay. However, the molecular mechanism by which NRXN1 deletions impact neurodevelopment remains unclear. Here we used human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs) as models to investigate the functional impacts of NRXN1 knockdown. We first generated hiPSCs from skin fibroblasts and differentiated them into neural stem cells (NSCs). We reduced NRXN1 expression in NSCs via a controlled shRNAmir-based knockdown system during differentiation, and monitored the transcriptome alteration by RNA-Seq and quantitative PCR at several time points. Interestingly, half reduction of NRXN1 expression resulted in changes of expression levels for the cell adhesion pathway (20 genes, P = 2.8x10(-6)) and neuron differentiation pathway (13 genes, P = 2.1x10(-4)), implicating that single-gene perturbation can impact biological networks important for neurodevelopment. Furthermore, astrocyte marker GFAP was significantly reduced in a time dependent manner that correlated with NRXN1 reduction. This observation was reproduced in both hiPSCs and hESCs. In summary, based on in vitro models, NRXN1 deletions impact several biological processes during neurodevelopment, including synaptic adhesion and neuron differentiation. Our study highlights the utility of stem cell models in understanding the functional roles of copy number variations (CNVs) in conferring susceptibility to neurodevelopmental diseases. |
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Zilhka Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America |
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English |
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1932-6203 |
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PMID:23536886; PMCID:PMC3607566 |
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16899 |
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