121 results on '"Rosoklija G"'
Search Results
2. Genetic architecture of the human tryptophan hydroxylase 2 Gene: existence of neural isoforms and relevance for major depression
- Author
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Haghighi, F, Bach-Mizrachi, H, Huang, Y Y, Arango, V, Shi, S, Dwork, A J, Rosoklija, G, Sheng, H T, Morozova, I, Ju, J, Russo, J J, and Mann, J J
- Published
- 2008
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3. Local activation of the complement system in endoneurial microvessels of diabetic neuropathy
- Author
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Rosoklija, G. B., Dwork, A. J., Younger, D. S., Karlikaya, G., Latov, N., and Hays, A. P.
- Published
- 2000
- Full Text
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4. Fourth meeting of the European Neurological Society 25–29 June 1994 Barcelona, Spain: Abstracts of Symposia and free communications
- Author
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Harms, L., Bock, A., JÄnisch, W., Valdueza, J., Weber, J., Link, I., De Keyser, J., Goossens, A., Wilczak, N., Vedeler, C., Bjorge, L., Uvestad, E., Conti, G., Williams, K., Ginsberg, L., Rafique, S., Rapoport, S. I., Gershfeld, N. L., De La Meilleure, G., Crevits, L., Faiss, J. H., Heye, N., Blanke, J., Sackmann, A., Kastrup, O., Doornbos, R., van der Worp, H. B., Kappelle, L. J., Bar, P. R., Davie, C. A., Barker, G. J., Brenton, D., Miller, D. H., Thompson, A. J., Block, F., Schwarz, M., Delodovici, L., Baruzzi, F., Bonaldi, G., Dario, A., Marra, A., Mercuri, A., Dworzak, F., Cavallari, P., Confalonieri, P., Zuffi, M., Antozzi, C., Cornelio, F., Baldissera, F., Chassande, B., Ameri, A., Eymard, B., Poisson, M., Vérier, A., Brunet, P., Congia, S., Murgia, P. L., Cannas, A., Borghero, G., Uselli, S., Mellino, G., Ferrai, R., Lampis, R., Massa, R., Muzzetto, B., Giannini, F., Rossi, S., Cioni, R., d'Aniello, C., Guarneri, A., Battistini, N., Ceriani, F., Del Santo, A., Poloni, M., Campo, J. F., Iglesias, F., Guitera, M. V., Farinas, C., Pascual, J., Leno, C., Berciano, J., Thorpe, I. W., Kendall, B. E., McDonald, W. I., Moulignier, A., Dromer, F., Baudrimont, M., Dupont, B., Gozlan, J., El Amrani, M., Petit, J. C., Roullet, E., Sterzi, R., Causaran, R., Protti, A., Riva, M., Erminio, F., Arena, O., Villa, F., Maccagnano, E., Miletta, M., Spinelli, F., Ben-Hur, T., Weidenfeldl, J., Rao, N. S., Chari, C. C., Laforet, P., Matheron, S., Adams, D., Chemouilli, Ph., Desi, M., Said, G., Davous, P., Lionnet, F., Pulik, M., Genet, P., Rozenberg, F., Cartier, L. M., Castillo, J. L., Cea, J. G., Villagra, R., de Saint Martin, L., Mahieux, F., Manifacier, M. J., Mattos, K., Queiros, C., Publio, L., Vinhas, V., PeÇanha-Martins, A. C., Melo, A., Liska, U., Zifko, U., Budka, H., Drlicek, M., Grisold, W., Kaufmann, R., Kaiser, R., Czygan, M., Gomes, I., Jones, N., Cunha, S., EmbiruÇu, E. Katiane, Vieira, V., Araujo, I., Alexandra, M., Ferreira, A., Goes, J., Chemouilli, P., Israel-Biet, Masson, H., Lacroix, C., Gasnault, J., Hildebrandt-Müller, B., Oschmann, P., Krack, P., Willems, W. R., Dorndorf, W., Freitas, V., Bittencourt, A., Fernandes, D., Nascimento, M. H., Severo, M., Moraes, D., Muller, M., Hasert, K., Merkelbach, S., Schimrigk, K., van Oosten, B. W., Lai, M., Polman, C. H., Bertelsmann, F. W., Hodgkinson, S., Cabre, P. H., Volpe, L., Smadja, D., Vernant, J. P., Villaroya, H., Violleau, K., Younes-Chennoufi, A. Ben, Baumann, N., Villanueva-Hemandez, P., Ballabriga, J., Basart, E., Arbizu, T. X., Perez-Serra, J., Vinuels, F., Giron, J. M., Castilla, J. M., Redondo, L., Izquierdo, G., Lauer, K., Henneberg, A., Bittmann, N., Link, D., Wollinsky, K. H., Mobner, R., Fassbender, K., Kuhnen, J., Schwartz, A., Hennerici, M., Miller, A., Lider, O., Abramsky, O., Weiner, H. L., Offner, H., Vanderbark, A. A., Paoino, E., Fainardi, E., Addonizio, M. C., Ruppi, P., Tola, M. R., Granieri, E., Carreras, M., Sazdovitch, V., Joutel, A., Verdier-taillefer, M. H., Heinzlef, O., Radder, C., Tournier-Lasserve, E., Brenner, R. E., Munro, P. M. G., Williams, S. C. R., Bell, J. D., Hawkins, C. P., Filippi, M., Campi, A., Dousset, V., Canal, N., Comi, G., Zhu, J., Weber, F., Retska, R., List, J., Zhang, L., Brock, M., Taphoorn, M. J. B., Heimans, J. J., van der Veen, E. A., Karim, A. B. M. F., Sarazin, M., Argentino, N., Delattre, J. Y., Derkinderen, P., Buchwald, B., Schroter, G., Serve, G., Franke, C. H., Conrad, B., Kitchen, N. D., Thomas, D. G. T., Forman, A. D., Ang, Kie- Kian, Price, R., Stephens, C., Salmaggi, A., Nermni, R., Silvani, A., Forno, M. G., Luksch, R., Boiardi, A., Grzelec, H., Fryze, C., Nowacki, P., Zdziarska, B., Sanson, M., Merel, P., Richard, S., Rouleau, G., Thomas, G., Olsen, N. K., Pfeiffer, P., Egund, N., Bentzen, S. M., Johannesen, L., Mondrup, K., Rose, C., Zyluk, B., Wondrusch, E., Berger, O., Fast, N., Jellinger, K., Lindner, K., Urman, A., Thibault, J. L., Duyckaerts, Ch., Strik, H., Muller, B., Richter, E., Krauseneck, P., Steinbrecher, A., Schabet, M., Hess, C., Bamberg, M., Dichgans, J., Counsell, C. E., McLeod, M., Grant, R., Creel, G. B., Claus, D., Sieber, E., Engelhardt, A., Rechlin, T., Thierauf, P., Neubauer, U., Peresson, M., Di Giovacchino, G., Romani, G. L., Di Silverio, F., Danek, A., Kuffner, M., Hoermann, R., Schopohl, J., Laska, M., Heye, B., Zangaladze, A. T., Valls-SoIè, J., Cammarota, A., Alvarez, R., Tolosa, E., Hallett, M., Ulbricht, D., Ganslandt, O., Kober, H., Vieth, J., Grummich, P., Pongratz, H., Brigel, C., Fahlbusch, R., Serra, F. P., Palma, V., Nolfe, G., Buscaino, G. A., Rothstein, T. L., Gibson J. M., Morrison P. M., Collins A. D., Eiselt, M., Wagnur, H., Zwiener, U., Schindler, T., Efendi, H., Ertekin, C., Erfas, M., Larsson, L. E., Sirin, H., AraÇ, N., Toygar, A., Demir, Y., Seddigh, S., Vogt, T. H., Hundemer, H., Visbeck, A., Pastena, L., Faralli, F., Mainardi, G., Gagliardi, R., Linden, D., Berlit, P., Lopez, O. L., Becker, J. T., Jungreis, C., Brenner, R., Rezek, D., Dekesky, S. T., Estol, C., Boller, F., Fernandez, J. M., Mederer, S., Batlle, J., Turon, A., Codina, A., Hitzenberger, P., Vila, N., Valls-SolÇ, J., Chamorro, A., Pouget, J., Schmied, A., Morin, D., Azulay, J. Ph., Vedel, J. P., Montalt, J., Escudero, J., Barona, R., Campos, A., Varli, K., Ertem, E., Uludag, B., Yagiz, A., Privorkin, Z., Steinvil, Y., Kott, E., Combarros, O., Sanchez-Pernaute, R., Orizaola, P., Mokrusch, Th., Kutluaye, E., Selcuki, D., Ertikin, C., Zettl, U., Gold, R., Harvey, G. K., Hartung, H. P., Toyka, K. V., Wokke, J. H. J., Oey, P. L., Ippel, P. F., Jansen, G. H., Franssen, H., Toyooka, K., Fujimura, H., Ueno, S., Yoshikawa, H., Yorifuji, S., Yanagihara, T., Talamon, C., Tzourio, C., Kiefer, R., Jung, S., Toyka, K., Ruolt, I., Tranchant, C., Mohr, M., Warter, J. M., Younger, D. S., Rosoklija, G., Hays, A. P., Kurita, R., Hasegawa, O., Matsumto, M., Komiyama, A., Nara, Y., Oueslati, S., Belal, S., Turki, I., Ben Hamida, C., Hentati, F., Ben Hamida, M., Kwiecinski, H., Krolicki, L., Domzal-Stryga, A., Dellemijn, P. L. I., van Deventer, P., van Moll, B., Drogendijk, T., Vecht, Ch. J., Nemni S., Amadio, Fazio, R., Galardin, G., Delodovici, M. L., Peghi, E., Monticelli, M. L., Sessa, A., Viguera, M. L., Palomar, M., Gamez, J., Cervera, C., Navarro, C., Serena, J., Duran, I., Fernandez, A. L., Comabella, M., Nos, C., Rio, J., Montalban, J., Navarro, X., Verdu, E., Darbra, S., Buti, M., Mrabet, A., Fredj, M., Gouider, R., Tounsi, H., Khalfallah, N., Haddad, A., Dbaiss, T., Ghnassia, R., Rouillet, E., Chedru, F., Porsche, H., Strenge, H., Li, S. W., Young, Y. P., Garcia, A. A., Baron, P., Scarpini, E., Bianchi, R., Conti, A., Livraghi, S., Rees, J. H., Gregson, N. A., Hughes, R. A. C., Sedano, M. J., Calleja, J., Canga, E., Bahou, Y., Biary, N., Al Deeb, S. M., Guern, E. L. E., Gugenheim, M., Tardieu, S., Aisonobe, T. M., Agid, Y., Bouche, P., Brice, A., Rautenstrauss, B., Nelis, E., Grehl, H., Van Broeckhoven, C., Pfeiffer, R. A., Liehr, T., Ganzmann, E., Gehring, C., Neundörfer, B., Geremia, L., Doronzo, R., Sacilotto, G., Sergi, P., Pastorino, G. C., Scarlato, G., Planté-Bordeneuve, V., Mantel, A., Baas, F., Moser, H., Antonini, A., Psylla, M., Günther, I., Vontobell, P., Beer, H. F., Leenders, K. L., Chaudhuri, K. Ray, Parker, J., Pye, I. F., Millac, P. A. H., Abbott, R. J., Sutter, M., Albani, C., de Rijk, M. C., Breteler, M. M. B., Graveland, G. A., van der Mechè, F. G. A., Hofman, A., Keipes, M., Hilger, Ch., Diederich, N., Metz, H., Hentges, F., Pollak, P., Benabid, A. L., Limousin, P., Hoffmann, D., Benazzouz, A., Perret, J., Laihinen, A., Rinne, J. O., Ruottinen, H., Nagren, K., Lehikoinen, P., Oikonen, V., Ruotsalainen, U., Rinne, U. K., Cocozza, S., Pizzuti, A., Cavalcanti, F., Monticelli, A., Pianese, L., Redolfi, E., Paiau, F., Di Donato, S., Pandolfo, M., Palau, F., Monros, E., De Michele, G., Smeyers, P., Lopez-ArLandis, J., Uilchez, J., Filla, A., Genis, D., Matilla, T., Volpini, V., Blanchs, M. I., Davalos, A., Molins, A., Rosell, J., Estivill, X., De Jonghe, P., Smeyers, G., Krols, L., Mercelis, R., Hazan, J., Weissenbach, J., Martin, J. J., Warner, T. A. T., Williams, L., Orb, A. S., Harding, A. E., Giunti, P., Sweeney, M. G., Spadaro, M., Jodice, C., Novelletto, A., Malaspina, P., Frontali, M., Salmon, E., Gregoire, Del Fiore, Comar, Franck, G., Scheltens, P. H., Siegfried, K., Dartigues, E., De Deyn, P., Horn, R., Nelson, I., Hanna, M. G., Morgan-Hughes, J. A., Collinge, J., Palmer, M. S., Campbell, T., Mahal, S., Sidle, K., Humphreys, C., Tavitian, B., Pappata, S., Jobert, A., Crouzel, A. M., DiGiamberardino, L., Steimetz, G., Barbanti, P., Fabbrini, G., Salvatore, M., Buzzi, M. G., Di Piero, V., Petraroli, R., Sbriccoli, A., Pocchiari, M., Macchi, G., Lenzi, G. L., Spiegel, R., Maguire, P., Schmid, W., Ott, A., Bots, M. L., Grobbe, D. E., Hofman, A., Howard, R. S., Russell, S., Losseff, N., Hirsch, N. P., Couderc, R., Bailleul, S., Nargeot, M. C., Touchon, J., Picot, M. C., Rizzo, M., Watson, G., McGehee, D., Dingus, T., Kappos, L., Radü, E. W., Haas, J., Hartard, C. H., Spuler, S., Yousry, T., Voltz, R., Scheller, A., Holler, E., Hohlfeld, R., Scolding, N. J., Sussman, J., Kolar, O. J., Farlow, M. R., Rice, P. H., Zipp, F., Sotgiu, S., Weiss, E. H., Wekerle, H., Chalmers, R., Robertson, N., Compston, D. A. S., Martino, G., Clementi, E., Brambilla, E., Moiola, L., Martinelli, V., Colombo, B., Poggi, A., Rovaris, M., Grimaldi, L. M. E., Roth, M. P., Descoins, P., Ballivet, S., Ruidavets, J. B., Waubant, E., Nogueira, L., Cambon-Thomsen, A., Clanet, M., Leppert, D., Hauser, S., Lugaresi, A., Tartaro, A., D'aurelio, P., Befalo, L. L. O., Thomas, A., Malatesta, G., Gambi, D., Benedikz, J. E. G., Magnusson, H., Poser, C. M., Guomundsson, G., Bates, T. E., Davies, S. E. C., Clark, J. B., Landon, D. N., ùther, J. R., Rautenberg, W., Overgaard, K., Sereghy, T., Pedersen, H., Boysen, G., Diez-Tejedor, E., Carceller, F., Gutierrez, M., Lopez-Pajares, R., Roda, J. M., Chandra, B., Ricart, W., Gonzalez-Huix, F., Molina, A., Rundek, T., Demarin, V., De Reuck, J., Boon, P., Decoq, D., Strijckmans, K., Goethals, P., Lemahieu, I., Nibbio, A., Chabriat, H., Vahedi, K., Nagy, T., Verin, M., Mas, J. L., Julien, J., Ducrocq, X., Iba-Zizen, M. T., Cabanis, E. A., Bousser, M. G., Rolland, Y., Landgraf, F., Bompais, B., Lemaitre, M. H., Edan, G., Vorstrup, S., Knudsen, L., Olsen, K. Skovgaard, Videbaek, C., Schroeder, T., van Gijn, J., Jansen, H. M. L., Pruim, J., Paans, A. M. J., Willemsen, A. T. M., Hew, J. M., vd Vliet, A. M., Haaxma, R., Vaalburg, W., Minderhoud, J. M., Korf, J., Soudain, S. E., Ho, T. W., Mishu, B., Li, C. Y., Nachainkin, I., Gao, C. Y., Cornblath, D. R., Griffin, J. W., Asbury, A. K., Blaser, M. J., McKhann, G. M., Ho, T., Macko, C., Xue, P., Stadlan, E. M., Ramos-Alvarez, M., Valenciano, L., Visser, L. H., van der Meché, F. G. A., van Darn, P. A., Meulstee, J., Schmitz, P. I. M., Jacobs, B., Oomes, P. G., Kleyweg, R. P., Jacobs, B. C., Endtz, H. P., van Doorn, P. A., van der Mech, F. G. A., Van den Berg, L. H., Mollee, I., Logtenberg, T., Thomas, P. K., Plant, G., Baxter, P. J., Luis, R. Santiago, Matsumoto, M., Notermans, N. C., Wokke, J. H. J., Lokhorst, H. M., van der Graaf, Y., Jennekens, F. G. I., Azulay, J. P., Bille-Turg, F., Valentin, P., Farnarier, G. G., Pellissier, J. F., Serratrice, G., Quasthoff, S., Schneider, U., Grafe, P., Hilkens, P. H. E., Moll, J. W. B., van der Burg, M. E. L., Planting, A. S. T., van Putten, W. L. J., van den Bent, M. J., Birklein, F., Spitzer, A., Lang, E., Neundorfer, B., Diehl, R. R., Lücke, D., Smith, G. D. P., Mathias, C. J., Serra, J., Campera, M., Ochoa, J. L., Ray Chaudhuri, K., Pavitt, D., Alam, M., Handwerker, H. O., Bleasdale-Barr, K., Smith, G., Murray, N. M. F., Hawkins, P., Pepys, M., Gellera, C., DiDonato, S., Taroni, F., Uncini, A., Di Muzio, A., Servidei, S., Silvestri, G., Lodi, R., Iotti, S., Barbiroli, B., Morrissey, S. P., Borruat, F. X., Francis, D., Mosely, I., Hansen, H. C., Helmke, K., Kunze, K., Sadzot, B., Maquet, P., Lemaire, Plenevaux, Damhaut, Sommer, C., Myers, R. R., Berta, E., Mantegazza, R., Argov, Z., Shapira, Y., Wirguin, I., Beuuer, J., Franke, C., Roberts, M., Willison, H., Vincent, A., Newsom-Davis, J., Morrison, K. E., Damels, R., Francis, M., Campbell, L., Davies, K. E., Kohler, W., Bucka, C., Hertel, G., Kanovsky, P., Auer, D., Ackermann, H., Klose, U., Naegele, Th., Bien, S., Voigt, K., Fink, G. R., Stephan, K. M., Wise, R. J. S., Mullatti, N., Hewer, L., Frackowiak, R. S. J., Weiller, C. S., Rijnites, M., Jueptner, M., Bauermann, T., Krams, M., Diener, H. C., van Walderveen, M. A. A., Barkhof, F., Hommes, O. R., Valk, J., Willmer, J. P., Guzman, D. A., Passingham, R. E., Silbersweig, D., Ceballos-Baumann, A., Frith, C. D., Frackowiak, R., Lucas, C. H., Goullard, L., Marchau, M. J., Godefroy, O., Rondepierre, P. H., Chamas, E., Mounier-Vehier, F., Leys, D., Renato, J., Verdugo, M. S. C., Campero, M., Jose, L., Ochoa, D. S. C., Vivancos, F., Tejedor, E. Diez, Martinez, N., Roda, J., Frank, A., Barreiro, P., Satoh, Y., Nagata, K., Maeda, T., Hirata, Y., YalÇinerner, B., Ozkara, C., Ozer, F., Ozer, S., Hanoglu, L., Zunker, P., Pozo, J. L., Oberwittler, C., Schick, A., Buschmann, H. -Ch., Ringelstein, E. Bernd, Lara, M., Anzola, G. P., Magoni, M., Volta, G. Dalla, Tarasov, A., Feigin, V., Beaudry, M. G., Carrier, S., Chicoutimi, Henriques, I. L., Bogoussslavsky, J., van Melle, G., Mathieu, J., Perusse, L., Allard, P., Prevost, C., Cantin, L., Bouchard, J. M., De Braekeleer, M., Agbo, C., Neau, J. P., Tantot, A. M., Dary-Auriol, M., Ingrand, P., Gil, R., Baltadjiev, D., Zekin, D., Sabey, K., Gennaula, C. P., Pope, B. A., Caparros-Lefebvre, D., Girard-Buttaz, I., Pruvo, J. P., Petit, H., Hipola, D., Martin, M., Giménez-Roldan, S., Ivanez, V., Japaridze, G., Carrasco, J. L., Picomell, I., Herranz, J. L., Macias, J. A., Nieto, M., Noya, M., Oller, L., Kiteva-Trencevska, G., Delgado, M. R., Liu, H., Luengo, A., Parra, J., Colas, J., Fernandez, M. J., Manzanares, R., Kornhuber, M. E., Malashkhia, V., Orkodashili, G., Martinez, M., Bonaventura, I., Porta, G., Martinez, I., Fernandez, A., Aguilar, M., Masnou, P., Drouet, A., Dreyfus, M., Cartron, J., Morel-Kopp, M. C., Tchernia, G., Kaplan, C., Lammers, M. W., Hekster, Y. A., Keyser, A., Meinardi, H., Renier, W. O., Boon, P. A. J. M., Have, M. D., Kint, B., Cruz, P., Cadilha, A., Almeida, R., Goncalves, M., Pimenta, M., Ramos, L. M. P., Polder, T. W., Broere, C. A., Polman, L., Rother, I., Rother, M., Schlaug, G., Arnold, S., Holthausen, H., Wunderlich, G., Ebner, A., Luders, H., Witte, O. W., Seitz, R. J., Serra, L. L., Gallicchio, B., Rotondi, F., Wieshmann, U., Meierkord, H., Sabev, K., Di Carlo, V., Gueguen, B., Derouesné, Ch., Ancri, D., Bourdel, M. C., Guillou, S., Aliaga, R., Chornet, M. A., Rodrigo, A., Pascual, A. Pascual -Leone, Catala, M. D., Pascual-Leone, A., Benbadis, S. R., Dinner, D. S., Chelune, G. J., Lüders, H. O., Piedmonte, M. R., Blanco, T., Lopez, M. P., Romero, B., Deltoro, A., Pascual, A., Pascual, Leone, Bolgert, F., Josse, M. O., Tassan, P., Touze, E., Laplane, D., Godenberg, F., Brizioli, E., Del Gobbo, M., Pelliccioni, G., Scarpino, O., Durak, H., Damlacik, G., Tunca, Z., Fidaner, H., Yurekli, Y., Yemez, B., Kaygisiz, A., Anllo, E. A., Esperet, E., Giovagnoli, A. R., Casazza, M., Spreafico, R., Avanzini, G., Mascheroni, S., Vecchio, I., Tornali, C., Antonuzzo, A., Grasso, A. A., Bella, R., Pennisi, G., Raffaele, R., Broeckx, J., Schildermans, F., Hospers, W., Deberdt, W., Carney, J. M., Aksenova, M., Chen, M. S., Juncadella, M., Busquets, N., De la Fuente, I., Rodriguez, A., Rubio, F., Soler, R., Khati, C., Pillon, B., Deweer, B., Malapani, C., Malichard, N., Dubois, B., Rancurel, G., Lopez, D. L., Jungreia, G., DeKosky, S. T., Boiler, F., Weiller, C., Rijntjes, M., Mueller, S. P., Maguire, E. A., Burke, E. T., Staunton, H., Phillips, J., Rousseaux, M., Pena, J., Bertran, I., Santacruz, P., Lopez, R., Catafau, A., Lomena, F., Blesa, R., Rampello, L., Nicoletti, A., Cabaret, M., Lesoin, F., Steinling, M., Tournev, I., Maier-Hauff, K., Schroeder, M., Wolf, A., Cochin, J. P., Noel, I., Augustin, P., Auzou, P., Hannequin, D., Maria, V., Lopez-Bresnahan, Danielle, D. M., Antin-Ozerkis B. A., Bartels, E., Rodiek, S. O., Flugel, K. A., Campos, D. M., Salas-Puig, J., Del Rio, J. Sanhez, Vidal, J. A., Lahoz, C. H., Eraksoy, M., Barlas, O., Barlas, M., Bayindir, C., Ozcan, H., Birbamer, G., Gerstenbrand, F., Felber, S., Luz, G., Aichner, F., Seidel, G., Kaps, M., Hutzelmann, A., Gerriets, T., Kruggel, F., Martin, P. J., Gaunt, M. E., Abbot, R. J., Naylor, A. R., Meary, E., Dilouya, A., Meder, J. F., De Recondo, J., Lebtahi, R., Neff, K. W., Meairs, S., Viola, S., Matta, E., Aquilone, L., Rise, I. R., Authier, F. J., Kondo, H., Ghnassia, R. T., Degos, J. D., Gherardi, R. 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- 1994
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5. COMPLEMENT PROTEINS IN SURAL NERVE BIOPSIES IN DIABETIC NEUROPATHY
- Author
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Hays, A. P., Rosoklija, G., and Younger, D. S.
- Published
- 1996
6. SUBICULAR MAP-2 IMMUNOREACTIVITY IS DIMINISHED IN A VARIETY OF PSYCHIATRIC DISORDERS
- Author
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Rosoklija, G., Hays, A. P., Latov, N., Sadiq, S. A., Kaufman, M., Waniek, C., Keilp, J., Prohovnik, I., and Dwork, A. J.
- Published
- 1996
7. ALTERED SUBICULAR MAP-2 IMMUNOREACTIVITY IN SCHIZOPHRENIA: 196
- Author
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Rosoklija, G., Hays, A. P., Lalov, N., Waniek, C., Keilp, J., Wu, A., Sadiq, S. A., Gorman, J., Prohovnik, I., and Dwork, AJ.
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- 1995
8. Brain microglia in psychiatric disorders
- Author
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Mondelli, Valeria, Vernon, Anthony C, Turkheimer, Federico, Dazzan, Paola, Pariante, Carmine M, Frost, JL, Schafer, DP, Banati, RB, Newcombe, J, Gunn, RN, al., et, Tang, Y, Le, W, Estes, ML, McAllister, AK, Ransohoff, RM, Davalos, D, Grutzendler, J, Yang, G, Peferoen, LA, Vogel, DY, Ummenthum, K, Norden, DM, Trojanowski, PJ, Villanueva, E, Navarro, E, Godbout, JP, Kreisel, T, Frank, MG, Licht, T, Wachholz, S, Eßlinger, M, Plümper, J, Manitz, MP, Juckel, G, Friebe, A, Trépanier, MO, Hopperton, KE, Mizrahi, R, Mechawar, N, Bazinet, RP, Torres-Platas, SG, Cruceanu, C, Chen, GG, Turecki, G, Steiner, J, Bielau, H, Brisch, R, Schnieder, TP, Trencevska, I, Rosoklija, G, Fillman, SG, Cloonan, N, Catts, VS, Rupprecht, R, Papadopoulos, V, Rammes, G, Qiu, ZK, Li, MS, He, JL, Hannestad, J, Gallezot, JD, Schafbauer, T, Israel, I, Ohsiek, A, Al-Momani, E, Mirzaei, N, Tang, SP, Ashworth, S, Gulyás, B, Makkai, B, Kása, P, Turkheimer, FE, Rizzo, G, Bloomfield, PS, Owen, DR, Yeo, AJ, DellaGioia, N, Setiawan, E, Wilson, AA, Su, L, Faluyi, YO, Hong, YT, Haarman, BC, Lek, RF Riemersma-Van der, Groot, JC de, Berckel, BN van, Bossong, MG, Boellaard, R, Doorduin, J, Vries, EF de, Willemsen, AT, Dierckx, RA, Klein, HC, Takano, A, Arakawa, R, Ito, H, Kenk, M, Selvanathan, T, Rao, N, Selvaraj, S, Veronese, M, Coughlin, JM, Wang, Y, Ambinder, EB, Doef, TF van der, Witte, LD de, Sutterland, AL, Hafizi, S, Tseng, HH, Holmes, SE, Hinz, R, Drake, RJ, Yaqub, M, Schuitemaker, A, Edison, P, Pavese, N, Lockhart, A, Davis, B, Matthews, JC, Quarantelli, M, Laule, C, Vavasour, IM, Kolind, SH, Pasternak, O, Sochen, N, Gur, Y, Intrator, N, Assaf, Y, Andreasen, NC, Ehrhardt, JC, Swayze, VW, Supprian, T, Hofmann, E, Warmuth-Metz, M, Franzek, E, Becker, T, Pfefferbaum, A, Sullivan, EV, Hedehus, M, Moseley, M, Lim, KO, Mandl, RC, Schnack, HG, Luigjes, J, Cahn, W, Bagary, MS, Symms, MR, Barker, GJ, Mutsatsa, SH, Joyce, EM, Ron, MA, Foong, J, Maier, M, Brocklehurst, S, Miller, DH, Kubicki, M, Park, H, Westin, CF, Bouix, S, Dahlben, B, Oestreich, LK, Shenton, ME, Amato, D, Beasley, CL, Hahn, MK, Vernon, AC, Natesan, S, Modo, M, Kapur, S, Mondelli, V, Reininghaus, U, Kempton, MJ, Valmaggia, L, Baumeister, D, Lightman, SL, Pariante, CM, Danese, A, Moffitt, TE, Ambler, A, Poulton, R, Caspi, A, Akhtar, R, Ciufolini, S, Meyer, U, So, PW, Lythgoe, DJ, Cotel, MC, Lenartowicz, EM, Anacker, C, Calcia, MA, Bonsall, DR, Barichello, T, Howes, OD, Burke, NN, Fan, CY, Trang, T, McMahon, SB, Russa, F La, Bennett, DL, Püntener, U, Booth, SG, Perry, VH, Teeling, JL, Hahn, YK, Podhaizer, EM, Farris, SP, Miles, MF, Hauser, KF, Knapp, PE, Notter, T, Gschwind, T, Varga, B, Markó, K, Hádinger, N, Cattaneo, A, Ferrari, C, Uher, R, Belvederi, Murri M, Sandiego, CM, Pittman, B, Weber, MD, Sheridan, JF, Raison, CL, Rutherford, RE, Woolwine, BJ, Möller, T, Boddeke, HW, O'Connor, JC, Lawson, MA, André, C, Hinwood, M, Morandini, J, Day, TA, Walker, FR, Bard, F, Bhattacharya, A, Pae, CU, Marks, DM, Han, C, Patkar, AA, Oya, K, Kishi, T, Iwata, N, Pathology, NCA - Neuroinflamation, Molecular cell biology and Immunology, Gastroenterology and hepatology, CCA - Disease profiling, ICaR - Heartfailure and pulmonary arterial hypertension, ICaR - Ischemia and repair, NCA - Brain imaging technology, Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, Otolaryngology / Head & Neck Surgery, EMGO - Quality of care, AII - Infectious diseases, CCA - Imaging, and Neurology
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0301 basic medicine ,medicine.medical_specialty ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Humans ,Psychology ,In patient ,Psychiatry ,Biological Psychiatry ,Neuroinflammation ,Inflammation ,Microglia ,business.industry ,Macrophages ,Mental Disorders ,Brain ,Magnetic Resonance Imaging ,Psychiatry and Mental health ,030104 developmental biology ,medicine.anatomical_structure ,Psychosocial stress ,Treatment strategy ,Autopsy ,business ,Neuroscience ,030217 neurology & neurosurgery ,Stress, Psychological ,Immune activation - Abstract
SummaryThe role of immune activation in psychiatric disorders has attracted considerable attention over the past two decades, contributing to the rise of a new era for psychiatry. Microglia, the macrophages of the brain, are progressively becoming the main focus of the research in this field. In this Review, we assess the literature on microglia activation across different psychiatric disorders, including post-mortem and in-vivo studies in humans and experimental studies in animals. Although microglia activation has been noted in all types of psychiatric disorder, no association was seen with specific diagnostic categories. Furthermore, the findings from these studies highlight that not all psychiatric patients have microglial activation. Therefore, the cause of the neuroinflammation in these cohorts and its implications are unclear. We discuss psychosocial stress as one of the main factors determining microglial activation in patients with psychiatric disorders, and explore the relevance of these findings for future treatment strategies.
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- 2016
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9. Whole-transcriptome brain expression and exon-usage profiling in major depression and suicide: evidence for altered glial, endothelial and ATPase activity
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Pantazatos, S P, primary, Huang, Y-Y, additional, Rosoklija, G B, additional, Dwork, A J, additional, Arango, V, additional, and Mann, J J, additional
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- 2016
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10. Postnatal Day 2 to 11 Constitutes a 5-HT-Sensitive Period Impacting Adult mPFC Function
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Rebello, T. J., primary, Yu, Q., additional, Goodfellow, N. M., additional, Caffrey Cagliostro, M. K., additional, Teissier, A., additional, Morelli, E., additional, Demireva, E. Y., additional, Chemiakine, A., additional, Rosoklija, G. B., additional, Dwork, A. J., additional, Lambe, E. K., additional, Gingrich, J. A., additional, and Ansorge, M. S., additional
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- 2014
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11. P.2.d.027 Necessity of hippocampal neurogenesis for the therapeutic action of antidepressants in adult nonhuman primates
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Anderson, L.B., primary, Dwork, A.J., additional, Keegan, K.A., additional, Thirumangalakudi, L., additional, Lipira, C.M., additional, Lange, C.M., additional, Higley, J.D., additional, Rosoklija, G., additional, Coplan, J.D., additional, and Perera, T.D., additional
- Published
- 2011
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12. Type III Neuregulin-1 Is Required for Normal Sensorimotor Gating, Memory-Related Behaviors, and Corticostriatal Circuit Components
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Chen, Y.-J. J., primary, Johnson, M. A., additional, Lieberman, M. D., additional, Goodchild, R. E., additional, Schobel, S., additional, Lewandowski, N., additional, Rosoklija, G., additional, Liu, R.-C., additional, Gingrich, J. A., additional, Small, S., additional, Moore, H., additional, Dwork, A. J., additional, Talmage, D. A., additional, and Role, L. W., additional
- Published
- 2008
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13. Hemispheric asymmetry of the superior temporal cortex in postmortem schizophrenic and control brains
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Smiley, J.F., primary, Dwork, A.J., additional, Davceva, N., additional, Mancevski, B., additional, Duma, A., additional, Rosoklija, G., additional, and Javitt, D.C., additional
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- 2003
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14. Comparison of Golgi stains of human and non-human primates
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Dwork, A.J., primary, Perera, T., additional, Lisanby, S.H., additional, Aluwihare, P., additional, Coplan, J., additional, and Rosoklija, G., additional
- Published
- 2003
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15. Letters to the editor
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Marques, Wilson, primary, Barreira, Auilton Artunes, additional, Oh, Shin J., additional, Claussen, Gwendolyn C., additional, Wondrusch, Elizabeth, additional, Zifko, Udo, additional, Grisold, Wolfgang, additional, Drlicek, Markus, additional, Setinek, Ulrike, additional, St�bgen, Joerg-Patrick, additional, Venkatesh, Swamy, additional, Rao, Ambika, additional, Gupta, Ravinder, additional, Younger, David S., additional, Rosoklija, G., additional, Neinstedt, L. J., additional, Latov, N., additional, Jaffe, I. A., additional, and Hays, A. P., additional
- Published
- 1996
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16. Diabetic peripheral neuropathy: A clinicopathologic and immunohistochemical analysis of sural nerve biopsies
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Younger, D. S., primary, Rosoklija, G., additional, Hays, A.P., additional, Trojaborg, W., additional, and Latov, N., additional
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- 1996
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17. Peripheral Nerve Immunohistochemistry in Diabetic Neuropathy
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Younger, D.S., primary, Rosoklija, G., additional, and Hays, A., additional
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- 1996
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18. Conduction block associated with axonal degeneration in an experimental model
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Wirguin, I., primary, Rosoklija, G., additional, Trojaborg, W., additional, Hays, A.P., additional, and Latov, N., additional
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- 1995
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19. Axonal degeneration accompanied by conduction block induced by toxin mediated immune reactivity to GM1 ganglioside in rat nerves
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Wirguin, I., primary, Rosoklija, G., additional, Trojaborg, W., additional, Hays, A.P., additional, and Latov, N., additional
- Published
- 1995
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20. Letter to the editor
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Younger, D. S., primary, Rosoklija, G., additional, Hays, A. P., additional, Gilchrist, James M., additional, Pascoe, Melinda K., additional, Silbert, Peter L., additional, and Hermann, Robert C., additional
- Published
- 1995
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21. Diabetic muscle infarction
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Bodner, R. A., primary, Younger, David S., additional, and Rosoklija, G., additional
- Published
- 1994
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22. PSYCHIATRIC BRAIN COLLECTION IN MACEDONIA: GENERAL LESSONS FOR SCIENTIFIC COLLABORATION AMONG COUNTRIES OF DIFFERING WEALTH.
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Rosoklija G., Duma A., and Dwork A. J.
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- *
MEDICAL research , *BRAIN , *PSYCHIATRY , *MENTAL health , *FOREIGN partnerships - Abstract
Macedonia is a small country, and the current state has been independent for only 22 years. Medical research, which requires an extensive infrastructure, has been limited. We describe our experience in developing Macedonian research through a mutually beneficial collaboration between institutions in Macedonia and the United States. [ABSTRACT FROM AUTHOR]
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- 2013
23. Imbalances in T-cell subpopulations and survival in human gliomas
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Rosoklija, G., primary, Dzonov, I., additional, Kolevski, P., additional, Kuzmanovski, T., additional, and Mirčevski, M., additional
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- 1991
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24. Correlation between 5-HT1A mRNA expression and number of mitotic and progenitor cells in the human hippocampus
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Santiago, A. N., Kassir, S. A., Migliarini, S., Bakalian, M. J., Burke, K. M., Musolino, G., Palavicino-Maggio, C. B., Rosoklija, G. B., Dwork, A. J., Mann, J. J., Pasqualetti, M., Hen, R., Victoria Arango, and Boldrini, M.
25. Lithium increases neural progenitor cells and vascularization in the dentate gyrus of subjects with bipolar disorder
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Boldrini, M., Burke, K. M., Underwood, M. D., Rosoklija, G. B., Dwork, A. J., Mann, J. J., and Victoria Arango
26. Antidepressant treatment increases neural progenitor cells in the dentate gyrus of the hippocampus of patients with Major Depressive Disorder
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Maura Boldrini, Underwood, M. D., Hen, R., Lau, J., Palavicino-Maggio, C., Bakalian, M. J., Rosoklija, G. B., Dwork, A. J., Mann, J. J., and Arango, V.
27. Does increased superoxide dismutase activity really cause muscular dystrophy?
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Almer, Gabriele, Rosoklija, Gorazd, Hirano, Michio, Hays, Arthur P., Przedborski, Serge, Almer, G, Rosoklija, G, Hirano, M, Hays, A P, and Przedborski, S
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- 1999
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28. Immunolocalization of heat shock proteins in ragged-red fibers of patients with mitochondrial encephalomyopathies
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Sparaco, M., Rosoklija, G., Tanji, K., and Sciacco, M.
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- 1993
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29. Late-stage borreliosis and substance abuse.
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Bransfield RC, Goud Gadila SK, Kursawe LJ, Dwork AJ, Rosoklija G, Horn EJ, Cook MJ, and Embers ME
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Background: Infectious diseases can contribute to substance abuse. Here, a fatal case of borreliosis and substance abuse is reported. This patient had a history of multiple tick bites and increasing multisystem symptoms, yet diagnosis and treatment were delayed. He experimented with multiple substances including phencyclidine (PCP), an N-methyl-d-aspartate (NMDA) receptor antagonist that opposes NMDA agonism caused by Borrelia infection. During PCP withdrawal, he committed one homicide, two assaults, and suicide., Methods: Brain tissue was obtained from autopsy and stained for microglial activation and quinolinic acid (QA). Immunoflouresence (IFA) and fluorescence in situ hybridization (FISH) were used to identify the presence of pathogens in autopsy tissue., Results: Autopsy tissue evaluation demonstrated Borrelia in the pancreas by IFA and heart by IFA and FISH. Activated microglia and QA were found in the brain, indicating neuroinflammation. It is postulated that PCP withdrawal may exacerbate symptoms produced by Borrelia -induced biochemical imbalances in the brain. This combination may have greatly increased his acute homicidal and suicidal risk. Patient databases also demonstrated the risk of homicide or suicide in patients diagnosed with borreliosis and confirmed multiple symptoms in these patients, including chronic pain, anxiety, and anhedonia., Conclusions: Late-stage borreliosis is associated with multiple symptoms that may contribute to an increased risk of substance abuse and addictive disorders. More effective diagnosis and treatment of borreliosis, and attention to substance abuse potential may help reduce associated morbidity and mortality in patients with borreliosis, particularly in endemic areas., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Monica E. Embers, Liz Horn reports financial support was provided by Bay Area Lyme Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)
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- 2024
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30. Brain and blood transcriptome profiles delineate common genetic pathways across suicidal ideation and suicide.
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Sun S, Liu Q, Wang Z, Huang YY, Sublette ME, Dwork AJ, Rosoklija G, Ge Y, Galfalvy H, Mann JJ, and Haghighi F
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- Humans, Female, Male, Adult, Middle Aged, Gene Regulatory Networks genetics, Depression genetics, Depression blood, Inflammation genetics, Inflammation blood, Suicidal Ideation, Transcriptome genetics, Suicide psychology, Brain metabolism
- Abstract
Human genetic studies indicate that suicidal ideation and behavior are both heritable. Most studies have examined associations between aberrant gene expression and suicide behavior, but behavior risk is linked to the severity of suicidal ideation. Through a gene network approach, this study investigates how gene co-expression patterns are associated with suicidal ideation and severity using RNA-seq data in peripheral blood from 46 live participants with elevated suicidal ideation and 46 with no ideation. Associations with the presence of suicidal ideation were found within 18 co-expressed modules (p < 0.05), as well as in 3 co-expressed modules associated with suicidal ideation severity (p < 0.05, not explained by severity of depression). Suicidal ideation presence and severity-related gene modules with enrichment of genes involved in defense against microbial infection, inflammation, and adaptive immune response were identified and investigated using RNA-seq data from postmortem brain that revealed gene expression differences with moderate effect sizes in suicide decedents vs. non-suicides in white matter, but not gray matter. Findings support a role of brain and peripheral blood inflammation in suicide risk, showing that suicidal ideation presence and severity are associated with an inflammatory signature detectable in blood and brain, indicating a biological continuity between ideation and suicidal behavior that may underlie a common heritability., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
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- 2024
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31. Functional Architecture of Brain and Blood Transcriptome Delineate Biological Continuity Between Suicidal Ideation and Suicide.
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Sun S, Liu Q, Wang Z, Huang YY, Sublette M, Dwork A, Rosoklija G, Ge Y, Galfalvy H, Mann JJ, and Haghighi F
- Abstract
Human genetic studies indicate that suicidal ideation and behavior are both heritable. Most studies have examined associations between aberrant gene expression and suicide behavior, but behavior risk is linked to severity of suicidal ideation. Through a gene network approach, this study investigates how gene co-expression patterns are associated with suicidal ideation and severity using RNA-seq data in peripheral blood from 46 live participants with elevated suicidal ideation and 46 with no ideation. Associations with presence and severity of suicidal ideation were found within 18 and 3 co-expressed modules respectively (p < 0.05), not explained by severity of depression. Suicidal ideation presence and severity-related gene modules with enrichment of genes involved in defense against microbial infection, inflammation, and adaptive immune response were identified, and tested using RNA-seq data from postmortem brain that revealed gene expression differences in suicide decedents vs. non-suicides in white matter, but not gray matter. Findings support a role of brain and peripheral blood inflammation in suicide risk, showing that suicidal ideation presence and severity is associated with an inflammatory signature detectable in blood and brain, indicating a biological continuity between ideation and suicidal behavior that may underlie a common heritability., Competing Interests: Conflict of Interest: The authors declare no conflict of interest.
- Published
- 2023
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32. Comparison of sodium fluorescein and intraoperative ultrasonography in brain tumor resection.
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Sweeney JF, Rosoklija G, Sheldon BL, Bondoc M, Bandlamuri S, and Adamo MA
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- Adult, Humans, Fluorescein, Neoplasm, Residual, Retrospective Studies, Cohort Studies, Ultrasonography, Magnetic Resonance Imaging, Brain Neoplasms diagnostic imaging, Brain Neoplasms surgery, Brain Neoplasms pathology, Glioma pathology
- Abstract
Various intraoperative neuroimaging modalities are available to the neurosurgeon during brain tumor surgery. There remains no consensus on which modalities are superior. This retrospective, single-center cohort study directly compares sodium fluorescein (SF) and intraoperative ultrasonography (IOUS) as intraoperative imaging modalities in a sample of patients with glioblastoma isocitrate dehydrogenase 1 wildtype (GBM). Adult patients with GBM who underwent surgical resection using SF or IOUS guidance between 2010 and 2020 were included. Primary outcomes included extent of resection (EOR), post-operative residual tumor volume, gross total resection (GTR) rate, false negative assessments, and the incidence of new post-operative neurologic deficits. Additionally, pre-and post-test probabilities were calculated to assess each modality's ability to identify residual tumor. 98 patients met inclusion criteria (34 SF and 64 IOUS). Mean EOR was significantly higher for SF (94 ± 11 %) when compared to IOUS (87 ± 20 %; p = 0.032). Mean post-operative residual tumor was significantly higher for IOUS (197 ± 358 mm2) when compared to SF (81 ± 161mm
2 ; p = 0.038). GTR was more frequent with SF (62 % vs 46 %, p = 0.12). False negative assessments for residual tumor were more common with IOUS (22 % vs 15 %, p = 0.53). One patient in each group suffered a new neurologic deficit post-operatively (p = 0.58). Sensitivity, specificity, positive predictive value, and negative predictive value were 62 %, 100 %, 100 %, and 81 % for SF and 59 %, 100 %, 100 %, and 67 % for IOUS, respectively. Taken together, SF may be superior to IOUS in maximizing EOR in patients with GBM, however, both modalities appear to have good efficacy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)- Published
- 2022
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33. COVID-19 induces neuroinflammation and loss of hippocampal neurogenesis.
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Klein R, Soung A, Sissoko C, Nordvig A, Canoll P, Mariani M, Jiang X, Bricker T, Goldman J, Rosoklija G, Arango V, Underwood M, Mann JJ, Boon A, Dowrk A, and Boldrini M
- Abstract
Infection with the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is associated with onset of neurological and psychiatric symptoms during and after the acute phase of illness
1-4 . Acute SARS-CoV-2 disease (COVID-19) presents with deficits of memory, attention, movement coordination, and mood. The mechanisms of these central nervous system symptoms remain largely unknown.In an established hamster model of intranasal infection with SARS-CoV-25 , and patients deceased from COVID-19, we report a lack of viral neuroinvasion despite aberrant BBB permeability, microglial activation, and brain expression of interleukin (IL)-1β and IL-6, especially within the hippocampus and the inferior olivary nucleus of the medulla, when compared with non-COVID control hamsters and humans who died from other infections, cardiovascular disease, uremia or trauma. In the hippocampus dentate gyrus of both COVID-19 hamsters and humans, fewer cells expressed doublecortin, a marker of neuroblasts and immature neurons.Despite absence of viral neurotropism, we find SARS-CoV-2-induced inflammation, and hypoxia in humans, affect brain regions essential for fine motor function, learning, memory, and emotional responses, and result in loss of adult hippocampal neurogenesis. Neuroinflammation could affect cognition and behaviour via disruption of brain vasculature integrity, neurotransmission, and neurogenesis, acute effects that may persist in COVID-19 survivors with long-COVID symptoms.- Published
- 2021
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34. Detecting Borrelia Spirochetes: A Case Study With Validation Among Autopsy Specimens.
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Gadila SKG, Rosoklija G, Dwork AJ, Fallon BA, and Embers ME
- Abstract
The complex etiology of neurodegenerative disease has prompted studies on multiple mechanisms including genetic predisposition, brain biochemistry, immunological responses, and microbial insult. In particular, Lyme disease is often associated with neurocognitive impairment with variable manifestations between patients. We sought to develop methods to reliably detect Borrelia burgdorferi , the spirochete bacteria responsible for Lyme disease, in autopsy specimens of patients with a history of neurocognitive disease. In this report, we describe the use of multiple molecular detection techniques for this pathogen and its application to a case study of a Lyme disease patient. The patient had a history of Lyme disease, was treated with antibiotics, and years later developed chronic symptoms including dementia. The patient's pathology and clinical case description was consistent with Lewy body dementia. B. burgdorferi was identified by PCR in several CNS tissues and by immunofluorescent staining in the spinal cord. These studies offer proof of the principle that persistent infection with the Lyme disease spirochete may have lingering consequences on the CNS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gadila, Rosoklija, Dwork, Fallon and Embers.)
- Published
- 2021
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35. Comparative evaluation of two methods for LC-MS/MS proteomic analysis of formalin fixed and paraffin embedded tissues.
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Davalieva K, Kiprijanovska S, Dimovski A, Rosoklija G, and Dwork AJ
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- Chromatography, Liquid, Humans, Male, Paraffin Embedding, Reproducibility of Results, Tandem Mass Spectrometry, Tissue Fixation, Formaldehyde, Proteomics
- Abstract
The proteomics of formalin-fixed, paraffin-embedded (FFPE) samples has advanced significantly during the last two decades, but there are many protocols and few studies comparing them directly. There is no consensus on the most effective protocol for shotgun proteomic analysis. We compared the in-solution digestion with RapiGest and Filter Aided Sample Preparation (FASP) of FFPE prostate tissues stored 7 years and mirroring fresh frozen samples, using two label-free data-independent LC-MS/MS acquisitions. RapiGest identified more proteins than FASP, with almost identical numbers of proteins from fresh and FFPE tissues and 69% overlap, good preservation of high-MW proteins, no bias regarding isoelectric point, and greater technical reproducibility. On the other hand, FASP yielded 20% fewer protein identifications in FFPE than in fresh tissue, with 64-69% overlap, depletion of proteins >70 kDa, lower efficiency in acidic and neutral range, and lower technical reproducibility. Both protocols showed highly similar subcellular compartments distribution, highly similar percentages of extracted unique peptides from FFPE and fresh tissues and high positive correlation between the absolute quantitation values of fresh and FFPE proteins. In conclusion, RapiGest extraction of FFPE tissues delivers a proteome that closely resembles the fresh frozen proteome and should be preferred over FASP in biomarker and quantification studies. SIGNIFICANCE: Here we analyzed the performance of two sample preparation methods for shotgun proteomic analysis of FFPE tissues to give a comprehensive overview of the obtained proteomes and the resemblance to its matching fresh frozen counterparts. These findings give us better understanding towards competent proteomics analysis of FFPE tissues. It is hoped that it will encourage further assessments of available protocols before establishing the most effective protocol for shotgun proteomic FFPE tissue analysis., (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Published
- 2021
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36. Correlation Between Aspects of Perceived Patient Loneliness and Spinal Cord Stimulation Outcomes.
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Khazen O, Rosoklija G, Custozzo A, Gillogly M, Bridger C, Hobson E, Feustel P, Lambiase L, DiMarzio M, and Pilitsis JG
- Subjects
- Follow-Up Studies, Humans, Loneliness, Prospective Studies, Treatment Outcome, Spinal Cord Stimulation
- Abstract
Objectives: Loneliness as a whole has been characterized as a health-related risk factor and is associated with worse outcomes after cardiac procedures. Evidence suggests that chronic pain patients are particularly vulnerable to feeling lonely. We examined the relationship between different aspects of loneliness and one-year postoperative outcomes after spinal cord stimulation (SCS) for chronic pain., Materials and Methods: We contacted 69 patients with thoracic SCS who had participated in our prospective outcomes database with one-year follow-up to complete the validated, abbreviated UCLA Loneliness Scale (UCLA-3). We examined responses on question 9 of the Oswestry Disability Index (ODI), question 12 of the Beck Depression Inventory (BDI), and UCLA-3 due to their relevance to different aspects of loneliness. We conducted regression analyses to determine the relationship between aspects of loneliness and pain outcomes., Results: We identified that loss of interest in people, companionship, and feeling excluded were associated with pain outcomes. Loss of interest in people was associated with improvement in pain (NRS worst p = 0.021, r = 0.32, NRS least p = 0.004, r = 0.4; NRS right now p = 0.016, r = 0.33). Companionship and feeling excluded were also associated with pain. We examined the interface between depression and total loneliness and found that while both were related to each other, depression was not associated with pain outcomes., Conclusions: This study demonstrates an association between loss of interest in people, companionship, and feeling excluded and worse postoperative pain outcomes after receiving SCS. It identifies aspects of loneliness as important factors to consider when predicting the outcomes of SCS therapy for chronic pain control., (© 2020 International Neuromodulation Society.)
- Published
- 2021
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37. Correlations Between Family History of Psychiatric Illnesses and Outcomes of Spinal Cord Stimulation.
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Sheldon BL, Khazen O, Feustel PJ, Gechtman G, Rosoklija G, Patel S, DiMarzio M, Bridger C, Dentinger R, Slyer J, and Pilitsis JG
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- Family Health, Humans, Retrospective Studies, Treatment Outcome, Chronic Pain therapy, Mental Disorders therapy, Spinal Cord Stimulation
- Abstract
Objectives: Spinal cord stimulation (SCS) is a well-established procedure for chronic neuropathic pain. Research has established patients with personal psychiatric history do not fare as well as their correspondents following SCS surgery. We explored whether a documented psychiatric family history (PFH) correlated with worse outcomes following SCS surgery., Materials and Methods: We retrospectively reviewed our single-center, prospectively collected database of patients who received permanent SCS implants over the past eight years. Subjects were separated into those with documented PFH and those without. Subjects completed validated scales at preoperative, 6 ± 2 postoperative, and 12 ± 3 months postoperative visits. The percent change in scores from preoperative to postoperative timepoints was compared between subjects with PFH vs. controls., Results: SCS subjects reporting a PFH demonstrated significantly worse 6-month outcomes on Pain Catastrophizing Scale-rumination subscale (p = 0.02), numeric rating scale (NRS) scores on "pain at its least" (p = 0.04) and NRS "pain right now" (p = 0.02). This group also endorsed greater disability as measured by the Oswestry Disability Index (ODI) throughout the follow-up period (p = 0.04 at 6 ± 2 months, p = 0.001 at 12 ± 3 months)., Conclusions: Subjects with PFH may experience less improvement in disability following SCS as compared to subjects without PFH. They may take longer to achieve the same outcomes, including pain relief and decrease in pain rumination. Our findings show that improvements in the PFH cohort are equivalent to that of the no PFH cohort on all measures except ODI at 12-month follow-up. Thus obtaining a detailed PFH prior to performing SCS is important in order to implement pre-operative coping training for PFH patients, rather than exclusion from SCS., (© 2020 International Neuromodulation Society.)
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- 2020
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38. The SNAP25 Interactome in Ventromedial Caudate in Schizophrenia Includes the Mitochondrial Protein ARF1.
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Ramos-Miguel A, Barakauskas V, Alamri J, Miyauchi M, Barr AM, Beasley CL, Rosoklija G, Mann JJ, Dwork AJ, Moradian A, Morin GB, and Honer WG
- Subjects
- Adult, Aged, Caudate Nucleus physiopathology, Female, Humans, Male, Middle Aged, ADP-Ribosylation Factor 1 metabolism, Caudate Nucleus metabolism, Schizophrenia metabolism, Schizophrenia physiopathology, Synaptosomal-Associated Protein 25 metabolism
- Abstract
Abnormalities of SNAP25 (synaptosome-associated protein 25) amount and protein-protein interactions occur in schizophrenia, and may contribute to abnormalities of neurotransmitter release in patients. However, presynaptic terminal function depends on multiple subcellular mechanisms, including energy provided by mitochondria. To explore the SNAP25 interactome in schizophrenia, we immunoprecipitated SNAP25 along with interacting proteins from the ventromedial caudate of 15 cases of schizophrenia and 13 controls. Proteins were identified with mass spectrometry-based proteomics. As well as 15 SNARE- (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) associated proteins, we identified 17 mitochondria-associated and four other proteins. The mitochondrial small GTPase ARF1 (ADP-ribosylation factor 1) was identified in eight schizophrenia SNAP25 immunoprecipitates and none from controls (P = 0.004). Although the ARF1-SNAP25 interaction may be increased, immunoblotting demonstrated 21% lower ARF1-21 (21 kiloDaltons) in schizophrenia samples (P = 0.04). In contrast, the mitochondrial protein UQCRC1 (ubiquinol-cytochrome c reductase core protein 1) did not differ. Lower ARF1-21 levels were associated with the previously reported increased SNAP25-syntaxin interaction in schizophrenia (r = -0.39, P = 0.04). Additional immunoprecipitation studies confirmed the ARF1-21-SNAP25 interaction, independent of UQCRC1. Both ARF1 and SNAP25 were localized to synaptosomes. Confocal microscopy demonstrated co-localization of ARF1 and SNAP25, and further suggested fivefold enrichment of ARF1 in synaptosomes containing an excitatory marker (vesicular glutamate transporter) compared with synaptosomes containing an inhibitory marker (vesicular GABA transporter). The present findings suggest an association between abnormalities of SNARE proteins involved with vesicular neurotransmission and the mitochondrial protein ARF1 that may contribute to the pathophysiology of schizophrenia., (Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2019
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39. Reduced SNAP25 Protein Fragmentation Contributes to SNARE Complex Dysregulation in Schizophrenia Postmortem Brain.
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Ramos-Miguel A, Gicas K, Alamri J, Beasley CL, Dwork AJ, Mann JJ, Rosoklija G, Cai F, Song W, Barr AM, and Honer WG
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- Adult, Aged, Aged, 80 and over, Animals, Autopsy, Humans, Male, Middle Aged, Proteolysis, Rats, Rats, Sprague-Dawley, SNARE Proteins metabolism, Brain metabolism, Peptide Fragments metabolism, Schizophrenia metabolism, Synaptosomal-Associated Protein 25 metabolism
- Abstract
Recent studies associated schizophrenia with enhanced functionality of the presynaptic SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complex. Altered degradation pathways of the three core SNARE proteins: synaptosomal-associated protein 25 (SNAP25), syntaxin-1 and vesicle-associated membrane protein (VAMP) could contribute to enhanced complex function. To investigate these pathways, we first identified a 15-kDa SNAP25 fragment (f-S25) in human and rat brains, highly enriched in synaptosomal extractions, and mainly attached to cytosolic membranes with low hydrophobicity. The presence of f-S25 is consistent with reports of calpain-mediated SNAP25 cleavage. Co-immunoprecipitation assays showed that f-S25 retains the ability to bind syntaxin-1, which might prevent VAMP and/or Munc18-1 assembly into the complex. Quantitative analyses in postmortem human orbitofrontal cortex (OFC) revealed that schizophrenia (n = 35), but not major depression (n = 15), is associated with lower amounts of f-S25 (-37%, P = 0.027), and greater SNARE protein-protein interactions (35%, P < 0.001), compared with healthy matched controls (n = 28). Enhanced SNARE complex formation was strongly correlated with lower SNAP25 fragmentation rates (R = 0.563, P < 0.001). Statistical mediation analyses supported the hypothesis that reduced f-S25 density could upregulate SNARE fusion events in schizophrenia. Cortical calpain activity in schizophrenia did not differ from controls. f-S25 levels did not correlate with total calpain activity, indicating that if present, schizophrenia-related calpain dysfunction might occur locally at the presynaptic terminals. Overall, the present findings suggest the existence of an endogenous SNARE complex inhibitor related to SNAP25 proteolysis, associated with enhanced SNARE activity in schizophrenia., (Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2019
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40. Measurement-oriented deep-learning workflow for improved segmentation of myelin and axons in high-resolution images of human cerebral white matter.
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Janjic P, Petrovski K, Dolgoski B, Smiley J, Zdravkovski P, Pavlovski G, Jakjovski Z, Davceva N, Poposka V, Stankov A, Rosoklija G, Petrushevska G, Kocarev L, and Dwork AJ
- Subjects
- Autopsy, Humans, Workflow, Axons, Cerebrum diagnostic imaging, Deep Learning, Image Interpretation, Computer-Assisted methods, Microscopy, Electron methods, Myelin Sheath, White Matter diagnostic imaging
- Abstract
Background: Standard segmentation of high-contrast electron micrographs (EM) identifies myelin accurately but does not translate easily into measurements of individual axons and their myelin, even in cross-sections of parallel fibers. We describe automated segmentation and measurement of each myelinated axon and its sheath in EMs of arbitrarily oriented human white matter from autopsies., New Methods: Preliminary segmentation of myelin, axons and background by machine learning, using selected filters, precedes automated correction of systematic errors. Final segmentation is done by a deep neural network (DNN). Automated measurement of each putative fiber rejects measures encountering pre-defined artifacts and excludes fibers failing to satisfy pre-defined conditions., Results: Improved segmentation of three sets of 30 annotated images each (two sets from human prefrontal white matter and one from human optic nerve) is achieved with a DNN trained only with a subset of the first set from prefrontal white matter. Total number of myelinated axons identified by the DNN differed from expert segmentation by 0.2%, 2.9%, and -5.1%, respectively. G-ratios differed by 2.96%, 0.74% and 2.83%. Intraclass correlation coefficients between DNN and annotated segmentation were mostly >0.9, indicating nearly interchangeable performance., Comparison With Existing Method(s): Measurement-oriented studies of arbitrarily oriented fibers from central white matter are rare. Published methods are typically applied to cross-sections of fascicles and measure aggregated areas of myelin sheaths and axons, allowing estimation only of average g-ratio., Conclusions: Automated segmentation and measurement of axons and myelin is complex. We report a feasible approach that has so far proven comparable to manual segmentation., (Copyright © 2019 Elsevier B.V. All rights reserved.)
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- 2019
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41. Quantifying the relationship between symptoms at presentation and the prognosis of sarcoidosis.
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Judson MA, Preston S, Hu K, Zhang R, Jou S, Modi A, Sukhu I, Ilyas F, Rosoklija G, and Yucel R
- Subjects
- Adrenal Cortex Hormones therapeutic use, Adult, Aged, Case-Control Studies, Female, Follow-Up Studies, Humans, Incidental Findings, Male, Middle Aged, Prognosis, Quality of Life psychology, Radiography, Thoracic methods, Respiratory Function Tests methods, Retrospective Studies, Sarcoidosis drug therapy, Sarcoidosis, Pulmonary diagnostic imaging, Sarcoidosis, Pulmonary physiopathology, Spirometry methods, Sarcoidosis diagnosis, Sarcoidosis epidemiology, Sarcoidosis pathology, Sarcoidosis, Pulmonary pathology
- Abstract
Background: Although it is the general consensus that sarcoidosis patients who present with sarcoidosis-related symptoms have a worse outcome than patients whose disease is detected incidentally without symptoms, this premise has not been rigorously examined., Methods: Consecutive patients followed longitudinally at one US university sarcoidosis clinic were questioned concerning the onset and description of sarcoidosis-related symptoms at disease presentation. The patients were classified into those with no sarcoidosis-related symptoms at presentation (NSP group) and those with symptoms at presentation (SP group). The following outcomes were examined in the NSP and SP groups: most recent spirometry, organ involvement, need for sarcoidosis therapy, most recent health related quality of life (HRQOL) as measured by the Sarcoidosis Assessment Tool (SAT), most recent chest imaging Scadding stage results., Results: 660 sarcoidosis patients were analyzed, with 175 in the NSP group and 485 in the SP group. Compared to the NSP group, the SP group had a more frequent requirement for any sarcoidosis treatment, corticosteroid treatment, and non-corticosteroid treatment at some time and within the most recent year of follow up (at least 50% more than the NP group with strong statistical differences with p values all 0.01 or less). In addition, the SP group had significantly more organ involvement (p < 0.001) and several worse SAT domains (p < 0.022) than the NP group. There were no differences between the groups in terms of final spirometry or development of Scadding stage 4 chest radiographs. These findings held even after adjusting for age, sex, race, and time between presentation and the most recent follow-up visit using a multivariable logistic regression framework., Conclusions: In our sarcoidosis cohort, compared to the absence of symptoms at presentation, the presence of symptoms was associated with a greater need for treatment, more organ involvement, and worse HRQOL., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2019
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42. Blood Vessels and Perivascular Phagocytes of Prefrontal White and Gray Matter in Suicide.
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Schnieder TP, Zhou Qin ID, Trencevska-Ivanovska I, Rosoklija G, Stankov A, Pavlovski G, Mann JJ, and Dwork AJ
- Subjects
- Adult, Blood Vessels pathology, Female, Humans, Male, Middle Aged, Gray Matter pathology, Phagocytes pathology, Prefrontal Cortex pathology, Suicide, White Matter pathology
- Abstract
Inflammatory processes may contribute to psychiatric disorders and suicide. Earlier, we reported greater densities of perivascular phagocytes in dorsal prefrontal white matter (DPFWM) in suicide than in non-suicide deaths. To distinguish between greater vascularity and greater coverage of vessels by perivascular phagocytes, and to determine whether the excess of perivascular phagocytes is derived from microglia or from non-parenchymal immune cells, we made stereological estimates of vascular surface area density (AVTOTAL) by staining for glucose transporter Glut-1, and the fraction of vascular surface area (AF) immunoreactive (IR) for CD163 (CD163 AF) in dorsal and ventral prefrontal white and gray matter. Manner of death or psychiatric diagnosis showed no association with CD163 AF in any region. Suicide was associated with a lower AVTOTAL compared with non-suicides in DPFWM (p = 0.018) but not with AVTOTAL in the 3 other regions of interest. Thus, the earlier observation of increased density of perivascular phagocytes in DPFWM after suicide cannot be attributed to infiltration by peripheral monocytes or to increased vascularity. Greater AVTOTAL ventrally than dorsally (p = 0.002) was unique to suicide and white matter.
- Published
- 2019
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43. Publisher Correction: Mutations in Vps15 perturb neuronal migration in mice and are associated with neurodevelopmental disease in humans.
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Gstrein T, Edwards A, Přistoupilová A, Leca I, Breuss M, Pilat-Carotta S, Hansen AH, Tripathy R, Traunbauer AK, Hochstoeger T, Rosoklija G, Repic M, Landler L, Stránecký V, Dürnberger G, Keane TM, Zuber J, Adams DJ, Flint J, Honzik T, Gut M, Beltran S, Mechtler K, Sherr E, Kmoch S, Gut I, and Keays DA
- Abstract
In the supplementary information PDF originally posted, there were discrepancies from the integrated supplementary information that appeared in the HTML; the former has been corrected as follows. In the legend to Supplementary Fig. 2c, "major organs of the mouse" has been changed to "major organs of the adult mouse." In the legend to Supplementary Fig. 6d,h, "At E14.5 Mbe/Mbe mutants have a smaller percentage of Brdu positive cells in bin 3" has been changed to "At E14.5 Mbe/Mbe mutants have a higher percentage of Brdu positive cells in bin 3."
- Published
- 2018
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44. Mutations in Vps15 perturb neuronal migration in mice and are associated with neurodevelopmental disease in humans.
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Gstrein T, Edwards A, Přistoupilová A, Leca I, Breuss M, Pilat-Carotta S, Hansen AH, Tripathy R, Traunbauer AK, Hochstoeger T, Rosoklija G, Repic M, Landler L, Stránecký V, Dürnberger G, Keane TM, Zuber J, Adams DJ, Flint J, Honzik T, Gut M, Beltran S, Mechtler K, Sherr E, Kmoch S, Gut I, and Keays DA
- Subjects
- Alkylating Agents toxicity, Animals, Animals, Newborn, Atrophy chemically induced, Atrophy genetics, Atrophy pathology, Autophagy drug effects, Autophagy genetics, Brain drug effects, Brain pathology, Cell Movement drug effects, Disease Models, Animal, Embryo, Mammalian, Ethylnitrosourea toxicity, Female, Gene Expression Regulation, Developmental genetics, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neurons drug effects, Neurons ultrastructure, Signal Transduction drug effects, Signal Transduction genetics, Vacuolar Proton-Translocating ATPases drug effects, Cell Movement genetics, Gene Expression Regulation, Developmental drug effects, Mutation drug effects, Neurodevelopmental Disorders chemically induced, Neurodevelopmental Disorders diagnostic imaging, Neurodevelopmental Disorders genetics, Neurodevelopmental Disorders pathology, Neurons pathology, Vacuolar Proton-Translocating ATPases genetics
- Abstract
The formation of the vertebrate brain requires the generation, migration, differentiation and survival of neurons. Genetic mutations that perturb these critical cellular events can result in malformations of the telencephalon, providing a molecular window into brain development. Here we report the identification of an N-ethyl-N-nitrosourea-induced mouse mutant characterized by a fractured hippocampal pyramidal cell layer, attributable to defects in neuronal migration. We show that this is caused by a hypomorphic mutation in Vps15 that perturbs endosomal-lysosomal trafficking and autophagy, resulting in an upregulation of Nischarin, which inhibits Pak1 signaling. The complete ablation of Vps15 results in the accumulation of autophagic substrates, the induction of apoptosis and severe cortical atrophy. Finally, we report that mutations in VPS15 are associated with cortical atrophy and epilepsy in humans. These data highlight the importance of the Vps15-Vps34 complex and the Nischarin-Pak1 signaling hub in the development of the telencephalon.
- Published
- 2018
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45. In utero exposure to maternal smoking is associated with DNA methylation alterations and reduced neuronal content in the developing fetal brain.
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Chatterton Z, Hartley BJ, Seok MH, Mendelev N, Chen S, Milekic M, Rosoklija G, Stankov A, Trencevsja-Ivanovska I, Brennand K, Ge Y, Dwork AJ, and Haghighi F
- Subjects
- Brain pathology, Female, Fetal Development genetics, Fetus metabolism, GTP-Binding Protein alpha Subunits, Gq-G11 genetics, Gestational Age, Humans, Immunohistochemistry, Induced Pluripotent Stem Cells metabolism, Male, Neural Stem Cells cytology, Neural Stem Cells metabolism, Neurons metabolism, Pregnancy, Pregnancy Trimester, Second, Promoter Regions, Genetic, Succinate Dehydrogenase genetics, Tubulin genetics, Tubulin metabolism, Brain metabolism, DNA Methylation, Maternal Exposure, Smoking
- Abstract
Background: Intrauterine exposure to maternal smoking is linked to impaired executive function and behavioral problems in the offspring. Maternal smoking is associated with reduced fetal brain growth and smaller volume of cortical gray matter in childhood, indicating that prenatal exposure to tobacco may impact cortical development and manifest as behavioral problems. Cellular development is mediated by changes in epigenetic modifications such as DNA methylation, which can be affected by exposure to tobacco., Results: In this study, we sought to ascertain how maternal smoking during pregnancy affects global DNA methylation profiles of the developing dorsolateral prefrontal cortex (DLPFC) during the second trimester of gestation. When DLPFC methylation profiles (assayed via Illumina, HM450) of smoking-exposed and unexposed fetuses were compared, no differentially methylated regions (DMRs) passed the false discovery correction (FDR ≤ 0.05). However, the most significant DMRs were hypomethylated CpG Islands within the promoter regions of GNA15 and SDHAP3 of smoking-exposed fetuses. Interestingly, the developmental up-regulation of SDHAP3 mRNA was delayed in smoking-exposed fetuses. Interaction analysis between gestational age and smoking exposure identified significant DMRs annotated to SYCE3 , C21orf56 / LSS, SPAG1 and RNU12 / POLDIP3 that passed FDR. Furthermore, utilizing established methods to estimate cell proportions by DNA methylation, we found that exposed DLPFC samples contained a lower proportion of neurons in samples from fetuses exposed to maternal smoking. We also show through in vitro experiments that nicotine impedes the differentiation of neurons independent of cell death., Conclusions: We found evidence that intrauterine smoking exposure alters the developmental patterning of DNA methylation and gene expression and is associated with reduced mature neuronal content, effects that are likely driven by nicotine.
- Published
- 2017
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46. Quantitative mass spectrometry reveals changes in SNAP-25 isoforms in schizophrenia.
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Barakauskas VE, Moradian A, Barr AM, Beasley CL, Rosoklija G, Mann JJ, Ilievski B, Stankov A, Dwork AJ, Falkai P, Morin GB, and Honer WG
- Subjects
- Animals, Antipsychotic Agents pharmacology, Clozapine pharmacology, Female, Haloperidol pharmacology, Humans, Immunoprecipitation, Male, Mass Spectrometry, Middle Aged, Protein Isoforms, Rats, Sprague-Dawley, Schizophrenia drug therapy, Corpus Striatum metabolism, Schizophrenia metabolism, Synaptosomal-Associated Protein 25 metabolism
- Abstract
SNAP-25 and syntaxin are presynaptic terminal SNARE proteins altered in amount and function in schizophrenia. In the ventral caudate, we observed 32% lower SNAP-25 and 26% lower syntaxin, but greater interaction between the two proteins using an in vitro assay. SNAP-25 has two isoforms, SNAP-25A and B, differing by only 9 amino acids, but with different effects on neurotransmission. A quantitative mass spectrometry assay was developed to measure total SNAP-25, and proportions of SNAP-25A and B. The assay had a good linear range (50- to 150-fold) and coefficient of variation (4.5%). We studied ventral caudate samples from patients with schizophrenia (n=15) previously reported to have lower total SNAP-25 than controls (n=13). We confirmed 27% lower total SNAP-25 in schizophrenia, and observed 31% lower SNAP-25A (P=0.002) with 20% lower SNAP-25B amounts (P=0.10). Lower SNAP-25A amount correlated with greater SNAP-25-syntaxin protein-protein interactions (r=-0.41, P=0.03); the level of SNAP-25B did not. Administration of haloperidol or clozapine to rats did not mimic the changes found in schizophrenia. The findings suggest that lower levels of SNAP-25 in schizophrenia may represent a greater effect of the illness on the SNAP-25A isoform. This in turn could contribute to the greater interaction between SNAP25 and syntaxin, and possibly disturb neurotransmission in the illness., Competing Interests: None of the authors have a conflict of interest relevant to the subject of this paper. In addition to their primary employers: Dr. Clare Beasley received an honorarium from the Ontario Mental Health Foundation. Dr Alasdair Barr has acted as a consultant to Eli Lilly Canada. Dr J John Mann received grants from GlaxoSmithKline and Novartis. Dr Peter Falkai received fees for professional services from Astra Zeneca, BMS, Eisai, Eli Lilly, Lundbeck, Wyeth, and Jansen-Cilag. Dr William Honer has received consulting fees or sat on paid advisory boards for: MDH Consulting, In Silico, Novartis, Lundbeck and Roche; received honoraria from Rush University, the Korean Society for Schizophrenia Research, the Centre for Addiction and Mental Health (Toronto), the BC Schizophrenia Society, the Fraser, Vancouver Coastal and the Providence Health Authorities, and the Canadian Agency for Drugs and Technology in Health; and received grants from the Canadian Institutes of Health Research (CIHR). Drs. Barakauskas, Rosoklija, Ilievski, Stankov, Dwork, Moradian and Morin declare that, except for income received from their primary employers, no financial support or compensation was received from any individual or corporate entity over the past three years for research or professional service and there are no personal financial holdings that could be perceived as constituting a potential conflict of interest., (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Published
- 2016
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47. An objective measure combining physical and cognitive fatigability: Correlation with subjective fatigue in Parkinson's disease.
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Martino D, Tamburini T, Zis P, Rosoklija G, Abbruzzese G, Ray-Chaudhuri K, Pelosin E, and Avanzino L
- Subjects
- Adult, Aged, Aged, 80 and over, Analysis of Variance, Attention Deficit Disorder with Hyperactivity diagnosis, Attention Deficit Disorder with Hyperactivity etiology, Cues, Female, Fingers physiopathology, Humans, Male, Middle Aged, Motor Activity physiology, Movement physiology, Parkinson Disease psychology, Physical Examination, Cognition Disorders diagnosis, Cognition Disorders etiology, Fatigue diagnosis, Fatigue etiology, Parkinson Disease complications
- Abstract
Background: Objective measures of physical and cognitive fatigability do not correlate with subjective Parkinson's disease (PD)-related fatigue. The relationship of subjective PD-related fatigue to tasks combining cognitive and motor effort has never been explored., Methods: Forty-four right-handed, non-demented PD patients, 22 with (PD-F) and 22 without (PD-NF) fatigue, were tested using a sensor-engineered glove on their more affected hand. Patients performed sequential opposition finger movements following a metronome at 2 Hz for 5 min (cued task), and for another minute following a 2-min rest. The same task was repeated without sustained auditory cueing. Movement time (inter-tapping interval, ITI) and rate, touch duration, percentage of correct sequences and clinical measures (motor and fatigue severity, depression, sleep impairment and apathy) were analysed., Results: In the cued task, motor performance worsened over time (significantly increased ITI and decreased movement rate on the third to fifth minute) in PD-F patients only. In the uncued task, motor performance deteriorated similarly in the two groups. PD-F and PD-NF patients differed in ITI and movement rate deterioration over time only in the cued task, independently from motor severity, depression and sleep impairment. The severity of subjective fatigue complaints significantly correlated with motor performance deterioration in the cued task., Conclusions: PD-related fatigue is associated with performance on an externally cued, attention-controlled motor task, but not with an uncued version of the same task. The finding supports a link between PD-related fatigue and attention-demanding motor tasks, proposing a model of inducible fatigue applicable to future clinical and neuroimaging research., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2016
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48. Reduced GABA neuron density in auditory cerebral cortex of subjects with major depressive disorder.
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Smiley JF, Hackett TA, Bleiwas C, Petkova E, Stankov A, Mann JJ, Rosoklija G, and Dwork AJ
- Abstract
Although major depressive disorder (MDD) and schizophrenia (SZ) are closely associated with disrupted functions in frontal and limbic areas of cerebral cortex, cellular pathology has also been found in other brain areas, including primary sensory cortex. Auditory cortex is of particular interest, given the prominence of auditory hallucinations in SZ, and sensory deficits in MDD. We used stereological sampling methods in auditory cortex to look for cellular differences between MDD, SZ and non-psychiatric subjects. Additionally, as all of our MDD subjects died of suicide, we evaluated the association of suicide with our measurements by selecting a SZ sample that was divided between suicide and non-suicide subjects. Measurements were done in primary auditory cortex (area A1) and auditory association cortex (area Tpt), two areas with distinct roles in sensory processing and obvious differences in neuron density and size. In MDD, densities of GABAergic interneurons immunolabeled for calretinin (CR) and calbindin (CB) were 23-29% lower than non-psychiatric controls in both areas. Parvalbumin (PV) interneurons (counted only in area Tpt) showed a nominally smaller (16%) reduction that was not statistically significant. Total neuron and glia densities measured in Nissl stained sections did not show corresponding reductions. Analysis of suicide in the SZ sample indicated that reduced CR cell density was associated with suicide, whereas the densities of CB and other cells were not. Our results are consistent with previous studies in MDD that found altered GABA-associated markers throughout the cerebral cortex including primary sensory areas., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2016
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49. Increased SNARE Protein-Protein Interactions in Orbitofrontal and Anterior Cingulate Cortices in Schizophrenia.
- Author
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Ramos-Miguel A, Beasley CL, Dwork AJ, Mann JJ, Rosoklija G, Barr AM, and Honer WG
- Subjects
- Humans, Multiprotein Complexes metabolism, Presynaptic Terminals metabolism, Prospective Studies, Protein Binding, Gyrus Cinguli metabolism, Prefrontal Cortex metabolism, SNARE Proteins metabolism, Schizophrenia metabolism
- Abstract
Background: Synaptic dysfunction in schizophrenia may be associated with abnormal expression or function of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins (syntaxin, synaptosomal-associated protein 25 [SNAP25], vesicle-associated membrane protein [VAMP]) forming the molecular complex underlying neurosecretion. The impact of such abnormalities on efficient SNARE heterotrimer formation is poorly understood. We investigated putative SNARE dysfunction, along with possible roles for the SNARE binding partners Munc18-1, complexins (Cplx) 1/2, and synaptotagmin in brains from autopsies of individuals with and without schizophrenia., Methods: Postmortem samples were obtained from orbitofrontal cortex (OFC) and/or anterior cingulate cortex from two separate cohorts (n = 15 + 15 schizophrenia cases, n = 13 + 15 control subjects). SNARE interactions were studied by immunoprecipitation and one- or two-dimensional blue native polyacrylamide gel electrophoresis (BN-PAGE)., Results: In the first cohort, syntaxin, Munc18-1, and Cplx1, but not VAMP, Cplx2, or synaptotagmin, were twofold enriched in SNAP25 immunoprecipitated products from schizophrenia OFC in the absence of any alterations in total tissue homogenate levels of these proteins. In BN-PAGE, the SNARE heterotrimer was identified as a 150-kDa complex, increased in schizophrenia samples from cohort 1 (OFC: +45%; anterior cingulate cortex: +44%) and cohort 2 (OFC: +40%), with lower 70-kDa SNAP25-VAMP dimer (-37%) in the OFC. Upregulated 200-kDa SNARE-Cplx1 (+65%) and downregulated 550-kDa Cplx1-containing oligomers (-24%) in schizophrenia OFC were identified by BN-PAGE. These findings were not explained by postmortem interval, antipsychotic medication, or other potentially confounding variables., Conclusions: The findings support the hypothesis of upregulated SNARE complex formation in schizophrenia OFC, possibly favored by enhanced affinity for Munc18-1 and/or Cplx1. These alterations offer new therapeutic targets for schizophrenia., (Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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50. Visualisation of Microglia with the use of Immunohistochemical Double Staining Method for CD-68 and Iba-1 of Cerebral Tissue Samples in Cases of Brain Contusions.
- Author
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Stankov A, Belakaposka-Srpanova V, Bitoljanu N, Cakar L, Cakar Z, and Rosoklija G
- Subjects
- Biomarkers analysis, Brain pathology, Brain Injuries mortality, Brain Injuries pathology, Calcium-Binding Proteins, Case-Control Studies, Cell Shape, Humans, Microfilament Proteins, Microglia pathology, Predictive Value of Tests, Antigens, CD analysis, Antigens, Differentiation, Myelomonocytic analysis, Brain metabolism, Brain Injuries metabolism, DNA-Binding Proteins analysis, Immunohistochemistry, Microglia chemistry
- Abstract
In the recent years it has been confirmed that the main component of the immune response in an injury of the nerve cell comes from microglia and macrophages. The main challenge in the field of microglia research is to detect the different stages of cellular activation by visualization of the cell morphology. The existing visualization techniques are based on surface molecules expression in resting and activated microglia cells. For visualization of the microglial cells and their functional state we used double labeling method for cd-68 and iba1 in brain contusions with different survival time. Microglia are stained brown with Iba-1, whereas microglia impregnated with black, grainy color, represents activated microglia stained with CD 68. We had significantly positive results, and we were able to observe changes in the morphology of the microglia that correlated with the survival time. Using double labeling with Iba-1 and cd68 we were able to determine their physiological state based on the morphology and immunoreactivity.
- Published
- 2015
- Full Text
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