Atividade antiplasmodial e citotóxica in vitro da entrecasca do caule de Maytenus guianensis Klotzsch Ex Reissek

Species of the Maytenus genus (Celastraceae) are commonly used in folk medicine in the Amazon region against cancer and as an anti-inflammatory agent. Maytenus guianensis, popularly known as “chichuá” or “xixuá”, is a widespread tree in the Amazon rainforest. In this study, we investigated the acetone extract of the inner bark of this species regarding its cytotoxic activity against HepG2 cells and its antiplasmodial activity against the 3D7 strain of Plasmodium falciparum. Cytotoxicity was determined by the colorimetric method (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and the anti-P. falciparum activity was tested using anti-HRPII antibodies in an enzyme-linked immunosorbent assay. In the cytotoxicity assay, no cytotoxic activity was detected in any tested sample, according to the National Institute of Cancer standards. The results of the anti-P. falciparum  test, on the other hand, were promising (values expressed as IC50, in ng.mL-1): 253.02 ± 0.56 for the acetone extract of the inner bark, 292.23 ± 0.83 for the hexane fraction, 292.76 ± 0.51 for the chloroform fraction, 188.37 ± 0.74 for the acetone fraction, 837.04 ± 0.23 for friedelinol, and 950.25 ± 0.46 for 16 β-hydroxyfriedelin. Our results contributed with the chemotaxonomy of the Celastraceae and showed that M. guianensis may be an alternative source of compounds that could be used in prototypes of anti-malaria drugs.Espécies pertencentes ao gênero Maytenus (Celastraceae) são utilizadas na medicina tradicional na região Amazônica contra câncer, como anti-inflamatório. M. guianensis, popularmente conhecida como “chichuá e xixuá” é uma árvore muito difundida na floresta Amazônica. No presente estudo o extrato acetônico da entrecasca do caule desta espécie foi investigada acerca de sua atividade citotóxica nas células HepG2 e antiplasmodial no Plasmodium falciparum cepa 3D7. A citotoxicidade foi determinada através do método colorimétrico do (3-(4,5-dimetiltiazol-2-il)-2,5-difenil tetrazólio) e o teste anti-P. falciparum através do ensaio imunoenzimático anti-HRPII. Para o teste de atividade citotóxica nenhuma amostra testada apresentou citotoxicidade de acordo com o National Institute of Cancer. No teste anti-P. falciparum os resultados foram promissores e expressos em termos de IC50 (ng.mL-1), respectivamente: extrato acetônico da entrecasca do caule com 253,02 ± 0,56, fração hexânica com 292,23 ± 0,83, fração clorofórmica com 292,76 ± 0,01, fração acetônica com 188,37, friedelinol com 837,04 ± 0,05 e 16 β-hidroxifridelina com 950,25 ± 0,46. Os resultados obtidos contribuíram para o estudo quimiotaxonômico da família Celastraceae e mostrou que M. guianensis pode vir a ser uma fonte alternativa de compostos que poderão ser protótipos de drogas que atuarão frente à malária

In Vitro Antiplasmodial Activity of Flower Extracts from combretum leprosum mart (mofumbo)

Malaria is the cause of hundreds of deaths per year , besides putting billions of people at risk of developing disease. When it comes to its therapy, the drugs used currently are losing its efficacy due to increase inn the frequency of resistant strains of the parasite, highlight the importance for the serach of new classes of molecules prsentign antiplasmodial activity. In the present work, the antiplasmodial activities of five extracts from the flowers of Comretum leprosum are described. The method employed for obtaingine the extracts was silica gel column chromatography, and the techniques used for the analysis of antiplasmodial activity and citotoxicity were ELISA and MTT respectively, were a selectivitu index was calculated after the obtainign of these two values. The extract presenting the highest antiplasmodial activity was the chloroform extract, however, this extrac also presented the higther cytotoxicity and therefore the extract presenting the best overall activity was the hexane extract. The study deminstrated the plant Combretum leprosum has active substances against P. falciparum and therefore is a potential to be expored in funther pharmacological studies

Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign

Abstract: In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M ⊙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87’s spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded

Antimalarial ethnopharmacology in the Brazilian Amazon

The preoccupation to find new drugs for the treatment of malaria is increasing steadily due to the resistance of the parasite, which is a threat to disease control, The present study describes a literature review on the antimalarial ethnopharmacology (Anti-Plasmodium falciparum - in vitro) of the Brazilian Amazon plants, It was found a great diversity of plant species in the Brazilian Amazon with potential for research of new herbal and secondary metabolites with antiplasmodial action, in addition to treating other neglected parasitic diseases, However, for these studies is needed in addition to financial support, the interaction between different laboratories and research groups for the formation of multidisciplinary and interdisciplinary teams, which will enhance the research level in the region and increase the likelihood of new antimalarial drugs discovery

Antiplasmodial and antileishmanial activities of compounds from Piper tuberculatum Jacq fruits

Submitted by EMERSON LEAL ([email protected]) on 2019-08-23T20:27:45Z No. of bitstreams: 1 Antiplasmodial and antileishmanial activities of compounds from Piper tuberculatum Jacq fruit.pdf: 895929 bytes, checksum: a9023ba4e6b21258c8e08d5dad647429 (MD5)Approved for entry into archive by EMERSON LEAL ([email protected]) on 2019-08-23T20:41:30Z (GMT) No. of bitstreams: 1 Antiplasmodial and antileishmanial activities of compounds from Piper tuberculatum Jacq fruit.pdf: 895929 bytes, checksum: a9023ba4e6b21258c8e08d5dad647429 (MD5)Made available in DSpace on 2019-08-23T20:41:30Z (GMT). No. of bitstreams: 1 Antiplasmodial and antileishmanial activities of compounds from Piper tuberculatum Jacq fruit.pdf: 895929 bytes, checksum: a9023ba4e6b21258c8e08d5dad647429 (MD5) Previous issue date: 2018Faculdade de Educação e Cultura de Vilhena. Departamento de Biomedicina. Vilhena, RO, Brasil.Fundação Oswaldo Cruz. Plataforma de Bioensaios em Malária e Leishmaniose. Porto Velho, RO, Brasil.Fundação Oswaldo Cruz. Plataforma de Bioensaios em Malária e Leishmaniose. Porto Velho, RO, Brasil.Fundação Oswaldo Cruz. Plataforma de Bioensaios em Malária e Leishmaniose. Porto Velho, RO, Brasil.Fundação Oswaldo Cruz. Plataforma de Bioensaios em Malária e Leishmaniose. Porto Velho, RO, Brasil.Fundação Oswaldo Cruz. Plataforma de Bioensaios em Malária e Leishmaniose. Porto Velho, RO, Brasil.Fundação Oswaldo Cruz. Plataforma de Bioensaios em Malária e Leishmaniose. Porto Velho, RO, Brasil.Fundação Oswaldo Cruz. Plataforma de Bioensaios em Malária e Leishmaniose. Porto Velho, RO, Brasil.Fundação Universidade Federal de Rondônia. Departamento de Ciências Biológicas. Porto Velho, RO, Brasil.Fundação Oswaldo Cruz. Plataforma de Bioensaios em Malária e Leishmaniose. Porto Velho, RO, Brasil. / Centro Universitário São Lucas. Departamento de Ciências Biológicas. Porto Velho, RO, Brasil. / Instituto Nacional de Epidemiologia na Amazônia Ocidental. Porto Velho, RO, Brasil.Fundação Universidade Federal de Rondônia. Departamento de Química. Porto Velho, RO, Brasil.Introduction: This study assessed the activity of compounds from Piper tuberculatum against Plasmodium falciparum and Leishmania guyanensis. Methods: The effects of compounds from P. tuberculatum fruits on P. falciparum and L. guyanensis promastigote growth in vitro were determined. Hemolytic action and cytotoxicity in HepG2 and J774 cells were measured. Results: Three compounds showed strong antiplasmodial activity and one compound showed strong antileishmanial activity. Two compounds were non-toxic to HepG2 cells and all were toxic to J774 cells. The compounds showed no hemolytic activity. Conclusions: The tested compounds from P. tuberculatum exhibited antiparasitic and cytotoxic effects

Antiprotozoal action of synthetic cinnamic acid analogs

Submitted by EMERSON LEAL ([email protected]) on 2019-09-13T15:06:29Z No. of bitstreams: 1 Antiprotozoal action of synthetic cinnamic acid analogs.pdf: 1282999 bytes, checksum: 9055bccde66932ebd2ae36450ab4d6f5 (MD5)Approved for entry into archive by EMERSON LEAL ([email protected]) on 2019-09-13T15:27:30Z (GMT) No. of bitstreams: 1 Antiprotozoal action of synthetic cinnamic acid analogs.pdf: 1282999 bytes, checksum: 9055bccde66932ebd2ae36450ab4d6f5 (MD5)Made available in DSpace on 2019-09-13T15:27:30Z (GMT). No. of bitstreams: 1 Antiprotozoal action of synthetic cinnamic acid analogs.pdf: 1282999 bytes, checksum: 9055bccde66932ebd2ae36450ab4d6f5 (MD5) Previous issue date: 2018Fundação Oswaldo Cruz. Plataforma de Bioensaios em Malária e Leishmaniose. Porto Velho, RO, Brasil. / Universidade Federal de Rondônia. Programa de Pós-graduação em Biologia Experimental. Porto Velho, RO, Brasil. / Universidade Federal de Rondônia. Centro de Estudos de Biomoléculas Aplicadas à Saúde. Porto Velho, RO, Brasil.Fundação Oswaldo Cruz. Plataforma de Bioensaios em Malária e Leishmaniose. Porto Velho, RO, Brasil. / Centro Universitário São Lucas. Porto Velho, RO, Brasil.Fundação Oswaldo Cruz. Plataforma de Bioensaios em Malária e Leishmaniose. Porto Velho, RO, Brasil. / Universidade Federal de Rondônia. Programa de Pós-graduação em Biologia Experimental. Porto Velho, RO, Brasil. / Universidade Federal de Rondônia. Centro de Estudos de Biomoléculas Aplicadas à Saúde. Porto Velho, RO, Brasil.Universidade Federal de Rondônia. Programa de Pós-graduação em Biologia Experimental. Porto Velho, RO, Brasil. / Universidade Federal de Rondônia. Centro de Estudos de Biomoléculas Aplicadas à Saúde. Porto Velho, RO, Brasil. / Centro para el Desarrollo de Investigación Científica. Asunción, Paraguay.Universidade Federal de Rondônia. Programa de Pós-graduação em Biologia Experimental. Porto Velho, RO, Brasil. / Universidade Federal de Rondônia. Centro de Estudos de Biomoléculas Aplicadas à Saúde. Porto Velho, RO, Brasil. / Centro para el Desarrollo de Investigación Científica. Asunción, Paraguay.Centro para el Desarrollo de Investigación Científica. Asunción, Paraguay.Fundação Oswaldo Cruz. Plataforma de Bioensaios em Malária e Leishmaniose. Porto Velho, RO, Brasil. / Universidade Federal de Rondônia. Programa de Pós-graduação em Biologia Experimental. Porto Velho, RO, Brasil. / Centro Universitário São Lucas. Porto Velho, RO, Brasil. / Instituto Nacional de Epidemiologia na Amazônia Ocidental. Porto Velho, RO, Brasil.Fundação Oswaldo Cruz. Plataforma de Bioensaios em Malária e Leishmaniose. Porto Velho, RO, Brasil. / Universidade Federal de Rondônia. Programa de Pós-graduação em Biologia Experimental. Porto Velho, RO, Brasil. / Universidade Federal de Rondônia. Centro de Estudos de Biomoléculas Aplicadas à Saúde. Porto Velho, RO, Brasil.Introduction: Leishmaniasis, Chagas disease, and malaria cause morbidity globally. The drugs currently used for treatment have limitations. Activity of cinnamic acid analogs against Leishmania spp., Trypanosoma cruzi, and Plasmodium falciparum was evaluated in the interest of identifying new antiprotozoal compounds. Methods: In vitro effects of analogs against L. braziliensis, L. infantum chagasi, T. cruzi, and P. falciparum, and hemolytic and cytotoxic activities on NCTC 929 were determined. Results: Three analogs showed leishmanicidal and tripanocidal activity. No antiplasmodial, hemolytic, or cytotoxic activity was observed. Conclusions: Antiprotozoal activity of analogs against L. infantum braziliensis, L. infantum chagasi, and T. cruzi was demonstrated

In vitro and ex vivo antiplasmodial activity of 1-(3-benzyloxy-4-methoxy-phenyl)-3-(3,4,5-trimethoxy-phenyl)-propan-1-one) against circulating strains of Plasmodium spp. in the state of Rondônia, Brazil

Malaria is a disease caused by Plasmodium spp. protozoa. The ability of Plasmodium to develop resistance to current antimalarial drugs makes the study of chemotherapeutic alternatives extremely important. This study aimed to evaluate the antimalarial activity of compound 3286938 (1-(3-benzyloxy-4-methoxy-phenyl)-3-(3,4,5-trimethoxy-phenyl)-propan-1-one), which presents in its structure a 3,4,5-trimethoxyphenyl group, in vitro, using the W2 strain of P. falciparum and against circulating strains of P. vivax and P. falciparum from the state of Rondônia. The compound 3286938 obtained an IC50 of 24.4 µM against the W2 strain of P. falciparum, and against the circulating strains, it presented a median (MD)=38.7 µM for P. vivax and MD=6.7 µM for P. falciparum. As for toxicity, 3286938 showed CC50 > 500 µM for VERO and HepG2 strains with a selectivity index greater than 12.9, a ratio calculated for P. falciparum and P. vivax regarding Vero and HepG2 cells. The compound was not considered hemolytic in in vitro assays, thus indicating the specificity of its antiplasmodial action. Based on the results presented, and considering the unprecedented character of the compound, it can be concluded that 3286938 was shown to be promising for complementary in vitro and in vivo studies aiming to produce effective antiplasmodial action

Synergism of in vitro plasmodicidal activity of phospholipase A2 isoforms isolated from panamanian Bothrops asper venom

Bothrops asper is one of the most important snake species in Central America, mainly because of its medical importance in countries like Ecuador, Panama and Costa Rica, where this species causes a high number of snakebite accidents. Several basic phospholipases A2 (PLA2s) have been previously characterized from B. asper venom, but few studies have been carried out with its acidic isoforms. In addition, since snake venom is a rich source of bioactive substances, it is necessary to investigate the biotechnological potential of its components. In this context, this study aimed to carry out the biochemical characterization of PLA2 isoforms isolated from B. asper venom and to evaluate the antiparasitic potential of these toxins. The venom and key fractions were subjected to different chromatographic steps, obtaining nine PLA2s, four acidic ones (BaspAc-I, BaspAc-II, BaspAc-III and BaspAc-IV) and five basic ones (BaspB-I, BaspB-II, BaspB-III, BaspB-IV and BaspB-V). The isoelectric points of the acidic PLA2s were also determined, which presented values ranging between 4.5 and 5. The findings indicated the isolation of five unpublished isoforms, four Asp49-PLA, corresponding to the group of acidic isoforms, and one Lys49-PLA2-like. Acidic PLA2s catalyzed the degradation of all substrates evaluated; however, for the basic PLA2s, there was a preference for phosphatidylglycerol and phosphatidic acid. The antiparasitic potential of the toxins was evaluated, and the acidic PLA2s demonstrated action against the epimastigote forms of T. cruzi and promastigote forms of L. infantum, while the basic PLA2s BaspB-II and BaspB-IV showed activity against P. falciparum. The results indicated an increase of up to 10 times in antiplasmodial activity, when the Asp49-PLA2 and Lys49-PLA2 were associated with one another, denoting synergistic action between these PLA2 isoforms. These findings correspond to the first report of synergistic antiplasmodial action for svPLA2s, demonstrating that these molecules may be important targets in the search for new antiparasitic agent

Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign

746sireservedIn 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ~6.5 × 109M⊙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87's spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded.mixedAlgaba, J.C. and Anczarski, J. and Asada, K. and Baloković, M. and Chandra, S. and Cui, Y.-Z. and Falcone, A.D. and Giroletti, M. and Goddi, C. and Hada, K. and Haggard, D. and Jorstad, S. and Kaur, A. and Kawashima, T. and Keating, G. and Kim, J.-Y. and Kino, M. and Komossa, S. and Kravchenko, E.V. and Krichbaum, T.P. and Lee, S.-S. and Lu, R.-S. and Lucchini, M. and Markoff, S. and Neilsen, J. and Nowak, M.A. and Park, J. and Principe, G. and Ramakrishnan, V. and Reynolds, M.T. and Sasada, M. and Savchenko, S.S. and Williamson, K.E. and Akiyama, K. and Alberdi, A. and Alef, W. and Anantua, R. and Azulay, R. and Baczko, A.-K. and Ball, D. and Barrett, J. and Bintley, D. and Benson, B.A. and Blackburn, L. and Blundell, R. and Boland, W. and Bouman, K.L. and Bower, G.C. and Boyce, H. and Bremer, M. and Brinkerink, C.D. and Brissenden, R. and Britzen, S. and Broderick, A.E. and Broguiere, D. and Bronzwaer, T. and Byun, D.-Y. and Carlstrom, J.E. and Chael, A. and Chan, C.-K. and Chatterjee, S. and Chatterjee, K. and Chen, M.-T. and Chen, Y. and Chesler, P.M. and Cho, I. and Christian, P. and Conway, J.E. and Cordes, J.M. and Crawford, T.M. and Crew, G.B. and Cruz-Osorio, A. and Davelaar, J. and De Laurentis, M. and Deane, R. and Dempsey, J. and Desvignes, G. and Dexter, J. and Doeleman, S.S. and Eatough, R.P. and Falcke, H. and Farah, J. and Fish, V.L. and Fomalont, E. and Ford, H.A. and Fraga-Encinas, R. and Friberg, P. and Fromm, C.M. and Fuentes, A. and Galison, P. and Gammie, C.F. and García, R. and Gentaz, O. and Georgiev, B. and Gold, R. and Gómez, J.L. and Gómez-Ruiz, A.I. and Gu, M. and Gurwell, M. and Hecht, M.H. and Hesper, R. and Ho, L.C. and Ho, P. and Honma, M. and Huang, C.-W.L. and Huang, L. and Hughes, D.H. and Ikeda, S. and Inoue, M. and Issaoun, S. and James, D.J. and Jannuzi, B.T. and Janssen, M. and Jeter, B. and Jiang, W. and Jiménez-Rosales, A. and Johnson, M.D. and Jung, T. and Karami, M. and Karuppusamy, R. and Kettenis, M. and Kim, D.-J. and Kim, J. and Kim, J. and Koay, J.Y. and Kofuji, Y. and Koch, P.M. and Koyama, S. and Kramer, M. and Kramer, C. and Kuo, C.-Y. and Lauer, T.R. and Levis, A. and Li, Y.-R. and Li, Z. and Lindqvist, M. and Lico, R. and Lindahl, G. and Liu, J. and Liu, K. and Liuzzo, E. and Lo, W.-P. and Lobanov, A.P. and Loinard, L. and Lonsdale, C. and Macdonald, N.R. and Mao, J. and Marchili, N. and Marrone, D.P. and Marscher, A.P. and Martí-Vidal, I. and Matsushita, S. and Matthews, L.D. and Medeiros, L. and Menten, K.M. and Mizuno, I. and Mizuno, Y. and Moran, J.M. and Moriyama, K. and Moscibrodzka, M. and Müller, C. and Musoke, G. and Mejías, A.M. and Nagai, H. and Nagar, N.M. and Nakamura, M. and Narayan, R. and Narayanan, G. and Natarajan, I. and Nathanail, A. and Neri, R. and Ni, C. and Noutsos, A. and Okino, H. and Olivares, H. and Ortiz-León, G.N. and Oyama, T. and Ozel, F. and Palumbo, D.C.M. and Patel, N. and Pen, U.-L. and Pesce, D.W. and Piétu, V. and Plambeck, R. and Popstefanija, A. and Porth, O. and Pötzl, F.M. and Prather, B. and Preciado-López, J.A. and Psaltis, D. and Pu, H.-Y. and Rao, R. and Rawlings, M.G. and Raymond, A.W. and Rezzolla, L. and Ricarte, A. and Ripperda, B. and Roelofs, F. and Rogers, A. and Ros, E. and Rose, M. and Roshanineshat, A. and Rottmann, H. and Roy, A.L. and Ruszczyk, C. and Rygl, K.L.J. and Sánchez, S. and Sánchez-Arguelles, D. and Savolainen, T. and Schloerb, F.P. and Schuster, K.-F. and Shao, L. and Shen, Z. and Small, D. and Sohn, B.W. and Soohoo, J. and Sun, H. and Tazaki, F. and Tetarenko, A.J. and Tiede, P. and Tilanus, R.P.J. and Titus, M. and Toma, K. and Torne, P. and Trent, T. and Traianou, E. and Trippe, S. and Van Bemmel, I. and Van Langevelde, H.J. and Van Rossum, D.R. and Wagner, J. and Ward-Thompson, D. and Wardle, J. and Weintroub, J. and Wex, N. and Wharton, R. and Wielgus, M. and Wong, G.N. and Wu, Q. and Yoon, D. and Young, A. and Young, K. and Younsi, Z. and Yuan, F. and Yuan, Y.-F. and Zensus, J.A. and Zhao, G.-Y. and Zhao, S.-S. and Principe, G. and Giroletti, M. and D'Ammando, F. and Orienti, M. and Abdalla, H. and Adam, R. and Aharonian, F. and Benkhali, F.A. and Angüner, E.O. and Arcaro, C. and Armand, C. and Armstrong, T. and Ashkar, H. and Backes, M. and Baghmanyan, V. and Barbosa Martins, V. and Barnacka, A. and Barnard, M. and Becherini, Y. and Berge, D. and Bernlöhr, K. and Bi, B. and Böttcher, M. and Boisson, C. and Bolmont, J. and De Bony De Lavergne, M. and Breuhaus, M. and Brun, F. and Brun, P. and Bryan, M. and Büchele, M. and Bulik, T. and Bylund, T. and Caroff, S. and Carosi, A. and Casanova, S. and Chand, T. and Chen, A. and Cotter, G. and Curyło, M. and Damascene Mbarubucyeye, J. and Davids, I.D. and Davies, J. and Deil, C. and Devin, J. and Dewilt, P. and Dirson, L. and Djannati-Ataï, A. and Dmytriiev, A. and Donath, A. and Doroshenko, V. and Duffy, C. and Dyks, J. and Egberts, K. and Eichhorn, F. and Einecke, S. and Emery, G. and Ernenwein, J.-P. and Feijen, K. and Fegan, S. and Fiasson, A. and De Clairfontaine, G.F. and Fontaine, G. and Funk, S. and Füßling, M. and Gabici, S. and Gallant, Y.A. and Giavitto, G. and Giunti, L. and Glawion, D. and Glicenstein, J.F. and Gottschall, D. and Grondin, M.-H. and Hahn, J. and Haupt, M. and Hermann, G. and Hinton, J.A. and Hofmann, W. and Hoischen, C. and Holch, T.L. and Holler, M. and Hörbe, M. and Horns, D. and Huber, D. and Jamrozy, M. and Jankowsky, D. and Jankowsky, F. and Jardin-Blicq, A. and Joshi, V. and Jung-Richardt, I. and Kasai, E. and Kastendieck, M.A. and Katarzyński, K. and Katz, U. and Khangulyan, D. and Khélifi, B. and Klepser, S. and Kluźniak, W. and Komin, N. and Konno, R. and Kosack, K. and Kostunin, D. and Kreter, M. and Lamanna, G. and Lemiere, A. and Lemoine-Goumard, M. and Lenain, J.-P. and Levy, C. and Lohse, T. and Lypova, I. and Mackey, J. and Majumdar, J. and Malyshev, D. and Malyshev, D. and Marandon, V. and Marchegiani, P. and Marcowith, A. and Mares, A. and Martí-Devesa, G. and Marx, R. and Maurin, G. and Meintjes, P.J. and Meyer, M. and Moderski, R. and Mohamed, M. and Mohrmann, L. and Montanari, A. and Moore, C. and Morris, P. and Moulin, E. and Muller, J. and Murach, T. and Nakashima, K. and Nayerhoda, A. and De Naurois, M. and Ndiyavala, H. and Niederwanger, F. and Niemiec, J. and Oakes, L. and O'Brien, P. and Odaka, H. and Ohm, S. and Olivera-Nieto, L. and De Ona Wilhelmi, E. and Ostrowski, M. and Panter, M. and Panny, S. and Parsons, R.D. and Peron, G. and Peyaud, B. and Piel, Q. and Pita, S. and Poireau, V. and Noel, A.P. and Prokhorov, D.A. and Prokoph, H. and Pühlhofer, G. and Punch, M. and Quirrenbach, A. and Rauth, R. and Reichherzer, P. and Reimer, A. and Reimer, O. and Remy, Q. and Renaud, M. and Rieger, F. and Rinchiuso, L. and Romoli, C. and Rowell, G. and Rudak, B. and Ruiz-Velasco, E. and Sahakian, V. and Sailer, S. and Sanchez, D.A. and Santangelo, A. and Sasaki, M. and Scalici, M. and Schutte, H.M. and Schwanke, U. and Schwemmer, S. and Seglar-Arroyo, M. and Senniappan, M. and Seyffert, A.S. and Shafi, N. and Shiningayamwe, K. and Simoni, R. and Sinha, A. and Sol, H. and Specovius, A. and Spencer, S. and Spir-Jacob, M. and Stawarz, Ł. and Sun, L. and Steenkamp, R. and Stegmann, C. and Steinmassl, S. and Steppa, C. and Takahashi, T. and Tavernier, T. and Taylor, A.M. and Terrier, R. and Tiziani, D. and Tluczykont, M. and Tomankova, L. and Trichard, C. and Tsirou, M. and Tuffs, R. and Uchiyama, Y. and Van Der Walt, D.J. and Van Eldik, C. and Van Rensburg, C. and Van Soelen, B. and Vasileiadis, G. and Veh, J. and Venter, C. and Vincent, P. and Vink, J. and Völk, H.J. and Vuillaume, T. and Wadiasingh, Z. and Wagner, S.J. and Watson, J. and Werner, F. and White, R. and Wierzcholska, A. and Wong, Y.W. and Yusafzai, A. and Zacharias, M. and Zanin, R. and Zargaryan, D. and Zdziarski, A.A. and Zech, A. and Zhu, S.J. and Zorn, J. and Zouari, S. and Żywucka, N. and Acciari, V.A. and Ansoldi, S. and Antonelli, L.A. and Engels, A.A. and Artero, M. and Asano, K. and Baack, D. and Babić, A. and Baquero, A. and De Almeida, U.B. and Barrio, J.A. and Becerra González, J. and Bednarek, W. and Bellizzi, L. and Bernardini, E. and Bernardos, M. and Berti, A. and Besenrieder, J. and Bhattacharyya, W. and Bigongiari, C. and Biland, A. and Blanch, O. and Bonnoli, G. and Bošnjak, Ž. and Busetto, G. and Carosi, R. and Ceribella, G. and Cerruti, M. and Chai, Y. and Chilingarian, A. and Cikota, S. and Colak, S.M. and Colombo, E. and Contreras, J.L. and Cortina, J. and Covino, S. and D'Amico, G. and D'Elia, V. and Da Vela, P. and Dazzi, F. and De Angelis, A. and De Lotto, B. and Delfino, M. and Delgado, J. and Delgado Mendez, C. and Depaoli, D. and Di Pierro, F. and Di Venere, L. and Do Souto Espineira, E. and Dominis Prester, D. and Donini, A. and Dorner, D. and Doro, M. and Elsaesser, D. and Fallah Ramazani, V. and Fattorini, A. and Ferrara, G. and Fonseca, M.V. and Font, L. and Fruck, C. and Fukami, S. and García López, R.J. and Garczarczyk, M. and Gasparyan, S. and Gaug, M. and Giglietto, N. and Giordano, F. and Gliwny, P. and Godinović, N. and Green, J.G. and Green, D. and Hadasch, D. and Hahn, A. and Heckmann, L. and Herrera, J. and Hoang, J. and Hrupec, D. and Hütten, M. and Inada, T. and Inoue, S. and Ishio, K. and Iwamura, Y. and Jiménez, I. and Jormanainen, J. and Jouvin, L. and Kajiwara, Y. and Karjalainen, M. and Kerszberg, D. and Kobayashi, Y. and Kubo, H. and Kushida, J. and Lamastra, A. and Lelas, D. and Leone, F. and Lindfors, E. and Lombardi, S. and Longo, F. and López-Coto, R. and López-Moya, M. and López-Oramas, A. and Loporchio, S. and Machado De Oliveira Fraga, B. and Maggio, C. and Majumdar, P. and Makariev, M. and Mallamaci, M. and Maneva, G. and Manganaro, M. and Mannheim, K. and Maraschi, L. and Mariotti, M. and Martínez, M. and Mazin, D. and Menchiari, S. and Mender, S. and Mićanović, S. and Miceli, D. and Miener, T. and Minev, M. and Miranda, J.M. and Mirzoyan, R. and Molina, E. and Moralejo, A. and Morcuende, D. and Moreno, V. and Moretti, E. and Neustroev, V. and Nigro, C. and Nilsson, K. and Nishijima, K. and Noda, K. and Nozaki, S. and Ohtani, Y. and Oka, T. and Otero-Santos, J. and Paiano, S. and Palatiello, M. and Paneque, D. and Paoletti, R. and Paredes, J.M. and Pavletić, L. and Penil, P. and Perennes, C. and Persic, M. and Moroni, P.G.P. and Prandini, E. and Priyadarshi, C. and Puljak, I. and Rhode, W. and Ribó, M. and Rico, J. and Righi, C. and Rugliancich, A. and Saha, L. and Sahakyan, N. and Saito, T. and Sakurai, S. and Satalecka, K. and Saturni, F.G. and Schleicher, B. and Schmidt, K. and Schweizer, T. and Sitarek, J. and Šnidarić, I. and Sobczynska, D. and Spolon, A. and Stamerra, A. and Strom, D. and Strzys, M. and Suda, Y. and Surić, T. and Takahashi, M. and Tavecchio, F. and Temnikov, P. and Terzić, T. and Teshima, M. and Tosti, L. and Truzzi, S. and Tutone, A. and Ubach, S. and Van Scherpenberg, J. and Vanzo, G. and Vazquez Acosta, M. and Ventura, S. and Verguilov, V. and Vigorito, C.F. and Vitale, V. and Vovk, I. and Will, M. and Wunderlich, C. and Zarić, D. and Adams, C.B. and Benbow, W. and Brill, A. and Capasso, M. and Christiansen, J.L. and Chromey, A.J. and Daniel, M.K. and Errando, M. and Farrell, K.A. and Feng, Q. and Finley, J.P. and Fortson, L. and Furniss, A. and Gent, A. and Giuri, C. and Hassan, T. and Hervet, O. and Holder, J. and Hughes, G. and Humensky, T.B. and Jin, W. and Kaaret, P. and Kertzman, M. and Kieda, D. and Kumar, S. and Lang, M.J. and Lundy, M. and Maier, G. and Moriarty, P. and Mukherjee, R. and Nieto, D. and Nievas-Rosillo, M. and O'Brien, S. and Ong, R.A. and Otte, A.N. and Patel, S. and Pfrang, K. and Pohl, M. and Prado, R.R. and Pueschel, E. and Quinn, J. and Ragan, K. and Reynolds, P.T. and Ribeiro, D. and Richards, G.T. and Roache, E. and Rulten, C. and Ryan, J.L. and Santander, M. and Sembroski, G.H. and Shang, R. and Weinstein, A. and Williams, D.A. and Williamson, T.J. and Hirota, T. and Cui, L. and Niinuma, K. and Ro, H. and Sakai, N. and Sawada-Satoh, S. and Wajima, K. and Wang, N. and Liu, X. and Yonekura, Y.Algaba, J. C.; Anczarski, J.; Asada, K.; Baloković, M.; Ch, ; Ra, S.; Cui, Y. -Z.; Falcone, A. D.; Giroletti, M.; Goddi, C.; Hada, K.; Haggard, D.; Jorstad, S.; Kaur, A.; Kawashima, T.; Keating, G.; Kim, J. -Y.; Kino, M.; Komossa, S.; Kravchenko, E. V.; Krichbaum, T. P.; Lee, S. -S.; Lu, R. -S.; Lucchini, M.; Markoff, S.; Neilsen, J.; Nowak, M. A.; Park, J.; Principe, G.; Ramakrishnan, V.; Reynolds, M. T.; Sasada, M.; Savchenko, S. S.; Williamson, K. E.; Akiyama, K.; Alberdi, A.; Alef, W.; Anantua, R.; Azulay, R.; Baczko, A. -K.; Ball, D.; Barrett, J.; Bintley, D.; Benson, B. A.; Blackburn, L.; Blundell, R.; Bol, ; Bouman, K. L.; Bower, G. C.; Boyce, H.; Bremer, M.; Brinkerink, C. D.; Brissenden, R.; Britzen, S.; Broderick, A. E.; Broguiere, D.; Bronzwaer, T.; Byun, D. -Y.; Carlstrom, J. E.; Chael, A.; Chan, C. -K.; Chatterjee, S.; Chatterjee, K.; Chen, M. -T.; Chen, Y.; Chesler, P. M.; Cho, I.; Christian, P.; Conway, J. E.; Cordes, J. M.; Crawford, T. M.; Crew, G. B.; Cruz-Osorio, A.; Davelaar, J.; De Laurentis, M.; Deane, R.; Dempsey, J.; Desvignes, G.; Dexter, J.; Doeleman, S. S.; Eatough, R. P.; Falcke, H.; Farah, J.; Fish, V. L.; Fomalont, E.; Ford, H. A.; Fraga-Encinas, R.; Friberg, P.; Fromm, C. M.; Fuentes, A.; Galison, P.; Gammie, C. F.; García, R.; Gentaz, O.; Georgiev, B.; Gold, R.; Gómez, J. L.; Gómez-Ruiz, A. I.; Gu, M.; Gurwell, M.; Hecht, M. H.; Hesper, R.; Ho, L. C.; Ho, P.; Honma, M.; Huang, C. -W. L.; Huang, L.; Hughes, D. H.; Ikeda, S.; Inoue, M.; Issaoun, S.; James, D. J.; Jannuzi, B. T.; Janssen, M.; Jeter, B.; Jiang, W.; Jiménez-Rosales, A.; Johnson, M. D.; Jung, T.; Karami, M.; Karuppusamy, R.; Kettenis, M.; Kim, D. -J.; Kim, J.; Kim, J.; Koay, J. Y.; Kofuji, Y.; Koch, P. M.; Koyama, S.; Kramer, M.; Kramer, C.; Kuo, C. -Y.; Lauer, T. R.; Levis, A.; Li, Y. -R.; Li, Z.; Lindqvist, M.; Lico, R.; Lindahl, G.; Liu, J.; Liu, K.; Liuzzo, E.; Lo, W. -P.; Lobanov, A. P.; Loinard, L.; Lonsdale, C.; Macdonald, N. R.; Mao, J.; Marchili, N.; Marrone, D. P.; Marscher, A. P.; Martí-Vidal, I.; Matsushita, S.; Matthews, L. D.; Medeiros, L.; Menten, K. M.; Mizuno, I.; Mizuno, Y.; Moran, J. M.; Moriyama, K.; Moscibrodzka, M.; Müller, C.; Musoke, G.; Mejías, A. M.; Nagai, H.; Nagar, N. M.; Nakamura, M.; Narayan, R.; Narayanan, G.; Natarajan, I.; Nathanail, A.; Neri, R.; Ni, C.; Noutsos, A.; Okino, H.; Olivares, H.; Ortiz-León, G. N.; Oyama, T.; Ozel, F.; Palumbo, D. C. M.; Patel, N.; Pen, U. -L.; Pesce, D. W.; Piétu, V.; Plambeck, R.; Popstefanija, A.; Porth, O.; Pötzl, F. M.; Prather, B.; Preciado-López, J. A.; Psaltis, D.; Pu, H. -Y.; Rao, R.; Rawlings, M. G.; Raymond, A. W.; Rezzolla, L.; Ricarte, A.; Ripperda, B.; Roelofs, F.; Rogers, A.; Ros, E.; Rose, M.; Roshanineshat, A.; Rottmann, H.; Roy, A. L.; Ruszczyk, C.; Rygl, K. L. J.; Sánchez, S.; Sánchez-Arguelles, D.; Savolainen, T.; Schloerb, F. P.; Schuster, K. -F.; Shao, L.; Shen, Z.; Small, D.; Sohn, B. W.; Soohoo, J.; Sun, H.; Tazaki, F.; Tetarenko, A. J.; Tiede, P.; Tilanus, R. P. J.; Titus, M.; Toma, K.; Torne, P.; Trent, T.; Traianou, E.; Trippe, S.; Van Bemmel, I.; Van Langevelde, H. J.; Van Rossum, D. R.; Wagner, J.; Ward-Thompson, D.; Wardle, J.; Weintroub, J.; Wex, N.; Wharton, R.; Wielgus, M.; Wong, G. N.; Wu, Q.; Yoon, D.; Young, A.; Young, K.; Younsi, Z.; Yuan, F.; Yuan, Y. -F.; Zensus, J. A.; Zhao, G. -Y.; Zhao, S. -S.; Principe, G.; Giroletti, M.; D'Amm, ; O, F.; Orienti, M.; Abdalla, H.; Adam, R.; Aharonian, F.; Benkhali, F. A.; Angüner, E. O.; Arcaro, C.; Arm, ; Armstrong, T.; Ashkar, H.; Backes, M.; Baghmanyan, V.; Barbosa Martins, V.; Barnacka, A.; Barnard, M.; Becherini, Y.; Berge, D.; Bernlöhr, K.; Bi, B.; Böttcher, M.; Boisson, C.; Bolmont, J.; De Bony De Lavergne, M.; Breuhaus, M.; Brun, F.; Brun, P.; Bryan, M.; Büchele, M.; Bulik, T.; Bylund, T.; Caroff, S.; Carosi, A.; Casanova, S.; Ch, ; Chen, A.; Cotter, G.; Curyło, M.; Damascene Mbarubucyeye, J.; Davids, I. D.; Davies, J.; Deil, C.; Devin, J.; Dewilt, P.; Dirson, L.; Djannati-Ataï, A.; Dmytriiev, A.; Donath, A.; Doroshenko, V.; Duffy, C.; Dyks, J.; Egberts, K.; Eichhorn, F.; Einecke, S.; Emery, G.; Ernenwein, J. -P.; Feijen, K.; Fegan, S.; Fiasson, A.; De Clairfontaine, G. F.; Fontaine, G.; Funk, S.; Füßling, M.; Gabici, S.; Gallant, Y. A.; Giavitto, G.; Giunti, L.; Glawion, D.; Glicenstein, J. F.; Gottschall, D.; Grondin, M. -H.; Hahn, J.; Haupt, M.; Hermann, G.; Hinton, J. A.; Hofmann, W.; Hoischen, C.; Holch, T. L.; Holler, M.; Hörbe, M.; Horns, D.; Huber, D.; Jamrozy, M.; Jankowsky, D.; Jankowsky, F.; Jardin-Blicq, A.; Joshi, V.; Jung-Richardt, I.; Kasai, E.; Kastendieck, M. A.; Katarzyński, K.; Katz, U.; Khangulyan, D.; Khélifi, B.; Klepser, S.; Kluźniak, W.; Komin, N.; Konno, R.; Kosack, K.; Kostunin, D.; Kreter, M.; Lamanna, G.; Lemiere, A.; Lemoine-Goumard, M.; Lenain, J. -P.; Levy, C.; Lohse, T.; Lypova, I.; Mackey, J.; Majumdar, J.; Malyshev, D.; Malyshev, D.; Mar, ; On, V.; Marchegiani, P.; Marcowith, A.; Mares, A.; Martí-Devesa, G.; Marx, R.; Maurin, G.; Meintjes, P. J.; Meyer, M.; Moderski, R.; Mohamed, M.; Mohrmann, L.; Montanari, A.; Moore, C.; Morris, P.; Moulin, E.; Muller, J.; Murach, T.; Nakashima, K.; Nayerhoda, A.; De Naurois, M.; Ndiyavala, H.; Niederwanger, F.; Niemiec, J.; Oakes, L.; O'Brien, P.; Odaka, H.; Ohm, S.; Olivera-Nieto, L.; De Ona Wilhelmi, E.; Ostrowski, M.; Panter, M.; Panny, S.; Parsons, R. D.; Peron, G.; Peyaud, B.; Piel, Q.; Pita, S.; Poireau, V.; Noel, A. P.; Prokhorov, D. A.; Prokoph, H.; Pühlhofer, G.; Punch, M.; Quirrenbach, A.; Rauth, R.; Reichherzer, P.; Reimer, A.; Reimer, O.; Remy, Q.; Renaud, M.; Rieger, F.; Rinchiuso, L.; Romoli, C.; Rowell, G.; Rudak, B.; Ruiz-Velasco, E.; Sahakian, V.; Sailer, S.; Sanchez, D. A.; Santangelo, A.; Sasaki, M.; Scalici, M.; Schutte, H. M.; Schwanke, U.; Schwemmer, S.; Seglar-Arroyo, M.; Senniappan, M.; Seyffert, A. S.; Shafi, N.; Shiningayamwe, K.; Simoni, R.; Sinha, A.; Sol, H.; Specovius, A.; Spencer, S.; Spir-Jacob, M.; Stawarz, Ł.; Sun, L.; Steenkamp, R.; Stegmann, C.; Steinmassl, S.; Steppa, C.; Takahashi, T.; Tavernier, T.; Taylor, A. M.; Terrier, R.; Tiziani, D.; Tluczykont, M.; Tomankova, L.; Trichard, C.; Tsirou, M.; Tuffs, R.; Uchiyama, Y.; Van Der Walt, D. J.; Van Eldik, C.; Van Rensburg, C.; Van Soelen, B.; Vasileiadis, G.; Veh, J.; Venter, C.; Vincent, P.; Vink, J.; Völk, H. J.; Vuillaume, T.; Wadiasingh, Z.; Wagner, S. J.; Watson, J.; Werner, F.; White, R.; Wierzcholska, A.; Wong, Y. W.; Yusafzai, A.; Zacharias, M.; Zanin, R.; Zargaryan, D.; Zdziarski, A. A.; Zech, A.; Zhu, S. J.; Zorn, J.; Zouari, S.; Żywucka, N.; Acciari, V. A.; Ansoldi, S.; Antonelli, L. A.; Engels, A. A.; Artero, M.; Asano, K.; Baack, D.; Babić, A.; Baquero, A.; De Almeida, U. B.; Barrio, J. A.; Becerra González, J.; Bednarek, W.; Bellizzi, L.; Bernardini, E.; Bernardos, M.; Berti, A.; Besenrieder, J.; Bhattacharyya, W.; Bigongiari, C.; Bil, ; Blanch, O.; Bonnoli, G.; Bošnjak, Ž.; Busetto, G.; Carosi, R.; Ceribella, G.; Cerruti, M.; Chai, Y.; Chilingarian, A.; Cikota, S.; Colak, S. M.; Colombo, E.; Contreras, J. L.; Cortina, J.; Covino, S.; D'Amico, G.; D'Elia, V.; Da Vela, P.; Dazzi, F.; De Angelis, A.; De Lotto, B.; Delfino, M.; Delgado, J.; Delgado Mendez, C.; Depaoli, D.; Di Pierro, F.; Di Venere, L.; Do Souto Espineira, E.; Dominis Prester, D.; Donini, A.; Dorner, D.; Doro, M.; Elsaesser, D.; Fallah Ramazani, V.; Fattorini, A.; Ferrara, G.; Fonseca, M. V.; Font, L.; Fruck, C.; Fukami, S.; García López, R. J.; Garczarczyk, M.; Gasparyan, S.; Gaug, M.; Giglietto, N.; Giordano, F.; Gliwny, P.; Godinović, N.; Green, J. G.; Green, D.; Hadasch, D.; Hahn, A.; Heckmann, L.; Herrera, J.; Hoang, J.; Hrupec, D.; Hütten, M.; Inada, T.; Inoue, S.; Ishio, K.; Iwamura, Y.; Jiménez, I.; Jormanainen, J.; Jouvin, L.; Kajiwara, Y.; Karjalainen, M.; Kerszberg, D.; Kobayashi, Y.; Kubo, H.; Kushida, J.; Lamastra, A.; Lelas, D.; Leone, F.; Lindfors, E.; Lombardi, S.; Longo, F.; López-Coto, R.; López-Moya, M.; López-Oramas, A.; Loporchio, S.; Machado De Oliveira Fraga, B.; Maggio, C.; Majumdar, P.; Makariev, M.; Mallamaci, M.; Maneva, G.; Manganaro, M.; Mannheim, K.; Maraschi, L.;