2020 taxonomic update for phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales
Kuhn, Jens H. ; Adkins, Scott ; Alioto, Daniela ; Alkhovsky, Sergey V. ; Amarasinghe, Gaya K. ; Anthony, Simon J. ; Avšič-Županc, Tatjana ; Ayllón, María A. ; Bahl, Justin ; Balkema-Buschmann, Anne ; Ballinger, Matthew J. ; Bartonička, Tomáš ; Basler, Christopher ; Bavari, Sina ; Beer, Martin ; Bente, Dennis A. ; Bergeron, Éric ; Bird, Brian H. ; Blair, Carol ; Blasdell, Kim R. ; Bradfute, Steven B. ; Breyta, Rachel ; Briese, Thomas ; Brown, Paul A. ; Buchholz, Ursula J. ; Buchmeier, Michael J. ; Bukreyev, Alexander ; Burt, Felicity ; Buzkan, Nihal ; Calisher, Charles H. ; Cao, Mengji ; Casas, Inmaculada ; Chamberlain, John ; Chandran, Kartik ; Charrel, Rémi N. ; Chen, Biao ; Chiumenti, Michela ; Choi, Ryong ; Clegg, J.C.S. ; Crozier, Ian ; Graça, John V. da; Bó, Elena Dal; Dávila, Alberto M.R. ; Torre, Juan Carlos de la; Lamballerie, Xavier de; Swart, Rik L. de; Bello, Patrick L. Di; Paola, Nicholas Di; Serio, Francesco Di; Dietzgen, Ralf G. ; Digiaro, Michele ; Dolja, Valerian V. ; Dolnik, Olga ; Drebot, Michael A. ; Drexler, Jan Felix ; Dürrwald, Ralf ; Dufkova, Lucie ; Dundon, William G. ; Duprex, W.P. ; Dye, John M. ; Easton, Andrew J. ; Ebihara, Hideki ; Elbeaino, Toufic ; Ergünay, Koray ; Fernandes, Jorlan ; Fooks, Anthony R. ; Formenty, Pierre B.H. ; Forth, Leonie F. ; Fouchier, Ron A.M. ; Freitas-Astúa, Juliana ; Gago-Zachert, Selma ; Gāo, George Fú ; García, María Laura ; García-Sastre, Adolfo ; Garrison, Aura R. ; Gbakima, Aiah ; Goldstein, Tracey ; Gonzalez, Jean Paul J. ; Griffiths, Anthony ; Groschup, Martin H. ; Günther, Stephan ; Guterres, Alexandro ; Hall, Roy A. ; Hammond, John ; Hassan, Mohamed ; Hepojoki, Jussi ; Hepojoki, Satu ; Hetzel, Udo ; Hewson, Roger ; Hoffmann, Bernd ; Hongo, Seiji ; Höper, Dirk ; Horie, Masayuki ; Hughes, Holly R. ; Hyndman, Timothy H. ; Jambai, Amara ; Jardim, Rodrigo ; Jiāng, Dàohóng ; Jin, Qi ; Jonson, Gilda B. ; Junglen, Sandra ; Karadağ, Serpil ; Keller, Karen E. ; Klempa, Boris ; Klingström, Jonas ; Kobinger, Gary ; Kondō, Hideki ; Koonin, Eugene V. ; Krupovic, Mart ; Kurath, Gael ; Kuzmin, Ivan V. ; Laenen, Lies ; Lamb, Robert A. ; Lambert, Amy J. ; Langevin, Stanley L. ; Lee, Benhur ; Lemos, Elba R.S. ; Leroy, Eric M. ; Li, Dexin ; Lǐ, Jiànróng ; Liang, Mifang ; Liú, Wénwén ; Liú, Yàn ; Lukashevich, Igor S. ; Maes, Piet ; Marciel de Souza, William ; Marklewitz, Marco ; Marshall, Sergio H. ; Martelli, Giovanni P. ; Martin, Robert R. ; Marzano, Shin Yi L. ; Massart, Sébastien ; McCauley, John W. ; Mielke-Ehret, Nicole ; Minafra, Angelantonio ; Minutolo, Maria ; Mirazimi, Ali ; Mühlbach, Hans Peter ; Mühlberger, Elke ; Naidu, Rayapati ; Natsuaki, Tomohide ; Navarro, Beatriz ; Navarro, José A. ; Netesov, Sergey V. ; Neumann, Gabriele ; Nowotny, Norbert ; Nunes, Márcio R.T. ; Nylund, Are ; Økland, Arnfinn L. ; Oliveira, Renata C. ; Palacios, Gustavo ; Pallas, Vicente ; Pályi, Bernadett ; Papa, Anna ; Parrish, Colin R. ; Pauvolid-Corrêa, Alex ; Pawęska, Janusz T. ; Payne, Susan ; Pérez, Daniel R. ; Pfaff, Florian ; Radoshitzky, Sheli R. ; ul Rahman, Aziz ; Ramos-González, Pedro L. ; Resende, Renato O. ; Reyes, Carina A. ; Rima, Bertus K. ; Romanowski, Víctor ; Robles Luna, Gabriel ; Rota, Paul ; Rubbenstroth, Dennis ; Runstadler, Jonathan A. ; Ruzek, Daniel ; Sabanadzovic, Sead ; Salát, Jiří ; Sall, Amadou Alpha ; Salvato, Maria S. ; Sarpkaya, Kamil ; Sasaya, Takahide ; Schwemmle, Martin ; Shabbir, Muhammad Z. ; Shí, Xiǎohóng ; Shí, Zhènglì ; Shirako, Yukio ; Simmonds, Peter ; Širmarová, Jana ; Sironi, Manuela ; Smither, Sophie ; Smura, Teemu ; Song, Jin Won ; Spann, Kirsten M. ; Spengler, Jessica R. ; Stenglein, Mark D. ; Stone, David M. ; Straková, Petra ; Takada, Ayato ; Tesh, Robert B. ; Thornburg, Natalie J. ; Tomonaga, Keizō ; Tordo, Noël ; Towner, Jonathan S. ; Turina, Massimo ; Tzanetakis, Ioannis ; Ulrich, Rainer G. ; Vaira, Anna Maria ; Hoogen, Bernadette van den; Varsani, Arvind ; Vasilakis, Nikos ; Verbeek, Martin ; Wahl, Victoria ; Walker, Peter J. ; Wang, Hui ; Wang, Jianwei ; Wang, Xifeng ; Wang, Lin Fa ; Wèi, Tàiyún ; Wells, Heather ; Whitfield, Anna E. ; Williams, John V. ; Wolf, Yuri I. ; Wú, Zhìqiáng ; Yang, Xin ; Yáng, Xīnglóu ; Yu, Xuejie ; Yutin, Natalya ; Zerbini, Murilo ; Zhang, Tong ; Zhang, Yong Zhen ; Zhou, Guohui ; Zhou, Xueping - \ 2020
Archives of Virology 165 (2020). - ISSN 0304-8608 - p. 3023 - 3072.
In March 2020, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. At the genus rank, 20 new genera were added, two were deleted, one was moved, and three were renamed. At the species rank, 160 species were added, four were deleted, ten were moved and renamed, and 30 species were renamed. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.
The FLUXNET2015 dataset and the ONEFlux processing pipeline for eddy covariance data
Pastorello, Gilberto ; Trotta, Carlo ; Canfora, Eleonora ; Chu, Housen ; Christianson, Danielle ; Cheah, You Wei ; Poindexter, Cristina ; Chen, Jiquan ; Elbashandy, Abdelrahman ; Humphrey, Marty ; Isaac, Peter ; Polidori, Diego ; Ribeca, Alessio ; Ingen, Catharine van; Zhang, Leiming ; Amiro, Brian ; Ammann, Christof ; Arain, M.A. ; Ardö, Jonas ; Arkebauer, Timothy ; Arndt, Stefan K. ; Arriga, Nicola ; Aubinet, Marc ; Aurela, Mika ; Baldocchi, Dennis ; Barr, Alan ; Beamesderfer, Eric ; Marchesini, Luca Belelli ; Bergeron, Onil ; Beringer, Jason ; Bernhofer, Christian ; Berveiller, Daniel ; Billesbach, Dave ; Black, Thomas Andrew ; Blanken, Peter D. ; Bohrer, Gil ; Boike, Julia ; Bolstad, Paul V. ; Bonal, Damien ; Bonnefond, Jean Marc ; Bowling, David R. ; Bracho, Rosvel ; Brodeur, Jason ; Brümmer, Christian ; Buchmann, Nina ; Burban, Benoit ; Burns, Sean P. ; Buysse, Pauline ; Cale, Peter ; Cavagna, Mauro ; Cellier, Pierre ; Chen, Shiping ; Chini, Isaac ; Christensen, Torben R. ; Cleverly, James ; Collalti, Alessio ; Consalvo, Claudia ; Cook, Bruce D. ; Cook, David ; Coursolle, Carole ; Cremonese, Edoardo ; Curtis, Peter S. ; Andrea, Ettore D'; Rocha, Humberto da; Dai, Xiaoqin ; Davis, Kenneth J. ; Cinti, Bruno De; Grandcourt, Agnes de; Ligne, Anne De; Oliveira, Raimundo C. De; Delpierre, Nicolas ; Desai, Ankur R. ; Bella, Carlos Marcelo Di; Tommasi, Paul di; Dolman, Han ; Domingo, Francisco ; Dong, Gang ; Dore, Sabina ; Duce, Pierpaolo ; Dufrêne, Eric ; Dunn, Allison ; Dušek, Jiří ; Eamus, Derek ; Eichelmann, Uwe ; ElKhidir, Hatim Abdalla M. ; Eugster, Werner ; Ewenz, Cacilia M. ; Ewers, Brent ; Famulari, Daniela ; Fares, Silvano ; Feigenwinter, Iris ; Feitz, Andrew ; Fensholt, Rasmus ; Filippa, Gianluca ; Fischer, Marc ; Frank, John ; Galvagno, Marta ; Gharun, Mana ; Gianelle, Damiano ; Gielen, Bert ; Gioli, Beniamino ; Gitelson, Anatoly ; Goded, Ignacio ; Goeckede, Mathias ; Goldstein, Allen H. ; Gough, Christopher M. ; Goulden, Michael L. ; Graf, Alexander ; Griebel, Anne ; Gruening, Carsten ; Grünwald, Thomas ; Hammerle, Albin ; Han, Shijie ; Han, Xingguo ; Hansen, Birger Ulf ; Hanson, Chad ; Hatakka, Juha ; He, Yongtao ; Hehn, Markus ; Heinesch, Bernard ; Hinko-Najera, Nina ; Hörtnagl, Lukas ; Hutley, Lindsay ; Ibrom, Andreas ; Ikawa, Hiroki ; Jackowicz-Korczynski, Marcin ; Janouš, Dalibor ; Jans, Wilma ; Jassal, Rachhpal ; Jiang, Shicheng ; Kato, Tomomichi ; Khomik, Myroslava ; Klatt, Janina ; Knohl, Alexander ; Knox, Sara ; Kobayashi, Hideki ; Koerber, Georgia ; Kolle, Olaf ; Kosugi, Yoshiko ; Kotani, Ayumi ; Kowalski, Andrew ; Kruijt, Bart ; Kurbatova, Julia ; Kutsch, Werner L. ; Kwon, Hyojung ; Launiainen, Samuli ; Laurila, Tuomas ; Law, Bev ; Leuning, Ray ; Li, Yingnian ; Liddell, Michael ; Limousin, Jean Marc ; Lion, Marryanna ; Liska, Adam J. ; Lohila, Annalea ; López-Ballesteros, Ana ; López-Blanco, Efrén ; Loubet, Benjamin ; Loustau, Denis ; Lucas-Moffat, Antje ; Lüers, Johannes ; Ma, Siyan ; Macfarlane, Craig ; Magliulo, Vincenzo ; Maier, Regine ; Mammarella, Ivan ; Manca, Giovanni ; Marcolla, Barbara ; Margolis, Hank A. ; Marras, Serena ; Massman, William ; Mastepanov, Mikhail ; Matamala, Roser ; Matthes, Jaclyn Hatala ; Mazzenga, Francesco ; McCaughey, Harry ; McHugh, Ian ; McMillan, Andrew M.S. ; Merbold, Lutz ; Meyer, Wayne ; Meyers, Tilden ; Miller, Scott D. ; Minerbi, Stefano ; Moderow, Uta ; Monson, Russell K. ; Montagnani, Leonardo ; Moore, Caitlin E. ; Moors, Eddy ; Moreaux, Virginie ; Moureaux, Christine ; Munger, J.W. ; Nakai, Taro ; Neirynck, Johan ; Nesic, Zoran ; Nicolini, Giacomo ; Noormets, Asko ; Northwood, Matthew ; Nosetto, Marcelo ; Nouvellon, Yann ; Novick, Kimberly ; Oechel, Walter ; Olesen, Jørgen Eivind ; Ourcival, Jean Marc ; Papuga, Shirley A. ; Parmentier, Frans Jan ; Paul-Limoges, Eugenie ; Pavelka, Marian ; Peichl, Matthias ; Pendall, Elise ; Phillips, Richard P. ; Pilegaard, Kim ; Pirk, Norbert ; Posse, Gabriela ; Powell, Thomas ; Prasse, Heiko ; Prober, Suzanne M. ; Rambal, Serge ; Rannik, Üllar ; Raz-Yaseef, Naama ; Reed, David ; Dios, Victor Resco de; Restrepo-Coupe, Natalia ; Reverter, Borja R. ; Roland, Marilyn ; Sabbatini, Simone ; Sachs, Torsten ; Saleska, Scott R. ; Sánchez-Cañete, Enrique P. ; Sanchez-Mejia, Zulia M. ; Schmid, Hans Peter ; Schmidt, Marius ; Schneider, Karl ; Schrader, Frederik ; Schroder, Ivan ; Scott, Russell L. ; Sedlák, Pavel ; Serrano-Ortíz, Penélope ; Shao, Changliang ; Shi, Peili ; Shironya, Ivan ; Siebicke, Lukas ; Šigut, Ladislav ; Silberstein, Richard ; Sirca, Costantino ; Spano, Donatella ; Steinbrecher, Rainer ; Stevens, Robert M. ; Sturtevant, Cove ; Suyker, Andy ; Tagesson, Torbern ; Takanashi, Satoru ; Tang, Yanhong ; Tapper, Nigel ; Thom, Jonathan ; Tiedemann, Frank ; Tomassucci, Michele ; Tuovinen, Juha Pekka ; Urbanski, Shawn ; Valentini, Riccardo ; Molen, Michiel van der; Gorsel, Eva van; Huissteden, Ko van; Varlagin, Andrej ; Verfaillie, Joseph ; Vesala, Timo ; Vincke, Caroline ; Vitale, Domenico ; Vygodskaya, Natalia ; Walker, Jeffrey P. ; Walter-Shea, Elizabeth ; Wang, Huimin ; Weber, Robin ; Westermann, Sebastian ; Wille, Christian ; Wofsy, Steven ; Wohlfahrt, Georg ; Wolf, Sebastian ; Woodgate, William ; Li, Yuelin ; Zampedri, Roberto ; Zhang, Junhui ; Zhou, Guoyi ; Zona, Donatella ; Agarwal, Deb ; Biraud, Sebastien ; Torn, Margaret ; Papale, Dario - \ 2020
Scientific Data 7 (2020)1. - ISSN 2052-4463 - 1 p.
The FLUXNET2015 dataset provides ecosystem-scale data on CO2, water, and energy exchange between the biosphere and the atmosphere, and other meteorological and biological measurements, from 212 sites around the globe (over 1500 site-years, up to and including year 2014). These sites, independently managed and operated, voluntarily contributed their data to create global datasets. Data were quality controlled and processed using uniform methods, to improve consistency and intercomparability across sites. The dataset is already being used in a number of applications, including ecophysiology studies, remote sensing studies, and development of ecosystem and Earth system models. FLUXNET2015 includes derived-data products, such as gap-filled time series, ecosystem respiration and photosynthetic uptake estimates, estimation of uncertainties, and metadata about the measurements, presented for the first time in this paper. In addition, 206 of these sites are for the first time distributed under a Creative Commons (CC-BY 4.0) license. This paper details this enhanced dataset and the processing methods, now made available as open-source codes, making the dataset more accessible, transparent, and reproducible.
Antenatal multiple micronutrient supplementation: call to action for change in recommendation
Bourassa, Megan W. ; Osendarp, Saskia J.M. ; Adu‐Afarwuah, Seth ; Ahmed, Saima ; Ajello, Clayton ; Bergeron, Gilles ; Black, Robert ; Christian, Parul ; Cousens, Simon ; Pee, Saskia de; Dewey, Kathryn G. ; Arifeen, Shams El ; Engle‐Stone, Reina ; Fleet, Alison ; Gernand, Alison D. ; Hoddinott, John ; Klemm, Rolf ; Kraemer, Klaus ; Kupka, Roland ; McLean, Erin ; Moore, Sophie E. ; Neufeld, Lynnette M. ; Persson, L. ; Rasmussen, Kathleen M. ; Shankar, Anuraj H. ; Smith, Emily ; Sudfeld, Christopher R. ; Udomkesmalee, Emorn ; Vosti, Stephen A. - \ 2020
Annals of the New York Academy Of Sciences 1465 (2020)1. - ISSN 0077-8923 - p. 5 - 7.
Fostering the development of climate services through Copernicus Climate Change Service (C3S) for agriculture applications
Buontempo, Carlo ; Hutjes, Ronald ; Beavis, Philip ; Berckmans, Julie ; Cagnazzo, Chiara ; Vamborg, Freja ; Thépaut, Jean Noël ; Bergeron, Cedric ; Almond, Samuel ; Amici, Alessandro ; Ramasamy, Selvaraju ; Dee, Dick - \ 2020
Weather and Climate Extremes 27 (2020). - ISSN 2212-0947
Agriculture sector - Climate Data Store (CDS) - Copernicus Climate Change Services (C3S) - User-driven applications
To better understand and manage climate risks in climate-sensitive sectors such as agriculture, it is essential to have access to consistent and reliable data and information products. Tailoring these products to the needs of the users they want to serve facilitate informed decision-making and downstream applications. This requires an in-depth understanding of users' needs and the context in which these users operate. Considering the diversity of the economic sectors and their actors it is extremely challenging if not outright impossible to promote the emergence of climate services without empowering a plethora of intermediate users who can act as one of the steps in a potential long knowledge brokers chain that connect the climate data providers and the end-users. In this context, Copernicus Climate Change Service (C3S) has been designed around the Climate Data Store (CDS), a unique entry point to a huge variety of quality-controlled climate data and high-level utilities to process that data to develop user-driven applications. Through the Sectoral Information System, C3S has then developed a series of sector specific applications, which show how the infrastructure can be used to address specific users’ needs. This paper presents the key elements of the CDS and selected cases of sectoral application of C3S in agriculture.
Research agenda for preventing mosquito-transmitted diseases through improving the built environment in sub-Saharan Africa
Shenton, Fiona C. ; Addissie, Adamu ; Alabaster, Graham ; Baziwe, Dorothy ; Carrasco Tenezaca, Maria ; Chinula, Dingani ; Jatta, Ebrima ; Jawara, Musa ; Jones, Robert ; Knudsen, Jakob ; Krystosik, Amy R. ; Mccann, Robert ; Murima, N. ; Mutuku, Francis ; Nguela, Rachel Laure ; Nieto Sanchez, Claudia ; Nix, Emily ; Okumu, Fredros ; Ruel-bergeron, Sarah ; Spitzen, Jeroen ; Tusting, Lucy S. ; Wilson, Anne L. ; Wood, Hannah ; Zahouli Bi Zahouli, Julien ; Davies, Michael ; Lindsay, Steve W. - \ 2019
Cities & Health (2019). - ISSN 2374-8834 - 9 p.
Mosquito-transmitted diseases are a major threat to health in sub-Saharan Africa, but could be reduced through modifications to the built environment. Here we report findings from a major workshop held to identify the research gaps in this area, namely: (1) evidence of the health benefits to changes to the built environment, (2) understanding how mosquitoes enter buildings, (3) novel methods for reducing mosquito-house entry, (4) sustainable approaches for reducing mosquito habitats, (5) case studies of micro-financing for healthy homes and (6) methods for increasing scale-up. Multidisciplinary research is essential to build out mosquito-transmitted diseases, and not build them in.
Review of the evidence regarding the use of antenatal multiple micronutrient supplementation in low- and middle-income countries
Bourassa, Megan W. ; Osendarp, Saskia J.M. ; Adu-Afarwuah, Seth ; Ahmed, Saima ; Ajello, Clayton ; Bergeron, Gilles ; Black, Robert ; Christian, Parul ; Cousens, Simon ; Pee, Saskia de; Dewey, Kathryn G. ; Arifeen, Shams El ; Engle-Stone, Reina ; Fleet, Alison ; Gernand, Alison D. ; Hoddinott, John ; Klemm, Rolf ; Kraemer, Klaus ; Kupka, Roland ; McLean, Erin ; Moore, Sophie E. ; Neufeld, Lynnette M. ; Persson, Lars Åke ; Rasmussen, Kathleen M. ; Shankar, Anuraj H. ; Smith, Emily ; Sudfeld, Christopher R. ; Udomkesmalee, Emorn ; Vosti, Stephen A. - \ 2019
Annals of the New York Academy Of Sciences 1444 (2019)1. - ISSN 0077-8923 - p. 6 - 21.
LMICs - micronutrient - pregnancy - supplements
Inadequate micronutrient intakes are relatively common in low- and middle-income countries (LMICs), especially among pregnant women, who have increased micronutrient requirements. This can lead to an increase in adverse pregnancy and birth outcomes. This review presents the conclusions of a task force that set out to assess the prevalence of inadequate micronutrient intakes and adverse birth outcomes in LMICs; the data from trials comparing multiple micronutrient supplements (MMS) that contain iron and folic acid (IFA) with IFA supplements alone; the risks of reaching the upper intake levels with MMS; and the cost-effectiveness of MMS compared with IFA. Recent meta-analyses demonstrate that MMS can reduce the risks of preterm birth, low birth weight, and small for gestational age in comparison with IFA alone. An individual-participant data meta-analysis also revealed even greater benefits for anemic and underweight women and female infants. Importantly, there was no increased risk of harm for the pregnant women or their infants with MMS. These data suggest that countries with inadequate micronutrient intakes should consider supplementing pregnant women with MMS as a cost-effective method to reduce the risk of adverse birth outcomes.
sPlot – A new tool for global vegetation analyses
Bruelheide, Helge ; Dengler, Jürgen ; Jiménez-Alfaro, Borja ; Purschke, Oliver ; Hennekens, Stephan M. ; Chytrý, Milan ; Pillar, Valério D. ; Jansen, Florian ; Kattge, Jens ; Sandel, Brody ; Aubin, Isabelle ; Biurrun, Idoia ; Field, Richard ; Haider, Sylvia ; Jandt, Ute ; Lenoir, Jonathan ; Peet, Robert K. ; Peyre, Gwendolyn ; Sabatini, Francesco Maria ; Schmidt, Marco ; Schrodt, Franziska ; Winter, Marten ; Aćić, Svetlana ; Agrillo, Emiliano ; Alvarez, Miguel ; Ambarlı, Didem ; Angelini, Pierangela ; Apostolova, Iva ; Arfin Khan, Mohammed A.S. ; Arnst, Elise ; Attorre, Fabio ; Baraloto, Christopher ; Beckmann, Michael ; Berg, Christian ; Bergeron, Yves ; Bergmeier, Erwin ; Bjorkman, Anne D. ; Bondareva, Viktoria ; Borchardt, Peter ; Botta-Dukát, Zoltán ; Boyle, Brad ; Breen, Amy ; Brisse, Henry ; Byun, Chaeho ; Cabido, Marcelo R. ; Casella, Laura ; Cayuela, Luis ; Černý, Tomáš ; Chepinoga, Victor ; Csiky, János ; Curran, Michael ; Ćušterevska, Renata ; Dajić Stevanović, Zora ; Bie, Els De; Ruffray, Patrice de; Sanctis, Michele De; Dimopoulos, Panayotis ; Dressler, Stefan ; Ejrnæs, Rasmus ; El-Sheikh, Mohamed A.E.R.M. ; Enquist, Brian ; Ewald, Jörg ; Fagúndez, Jaime ; Finckh, Manfred ; Font, Xavier ; Forey, Estelle ; Fotiadis, Georgios ; García-Mijangos, Itziar ; Gasper, André Luis de; Golub, Valentin ; Gutierrez, Alvaro G. ; Hatim, Mohamed Z. ; He, Tianhua ; Higuchi, Pedro ; Holubová, Dana ; Hölzel, Norbert ; Homeier, Jürgen ; Indreica, Adrian ; Işık Gürsoy, Deniz ; Jansen, Steven ; Janssen, John ; Jedrzejek, Birgit ; Jiroušek, Martin ; Jürgens, Norbert ; Kącki, Zygmunt ; Kavgacı, Ali ; Kearsley, Elizabeth ; Kessler, Michael ; Knollová, Ilona ; Kolomiychuk, Vitaliy ; Korolyuk, Andrey ; Kozhevnikova, Maria ; Kozub, Łukasz ; Krstonošić, Daniel ; Kühl, Hjalmar ; Kühn, Ingolf ; Kuzemko, Anna ; Küzmič, Filip ; Landucci, Flavia ; Lee, Michael T. ; Levesley, Aurora ; Li, Ching Feng ; Liu, Hongyan ; Lopez-Gonzalez, Gabriela ; Lysenko, Tatiana ; Macanović, Armin ; Mahdavi, Parastoo ; Manning, Peter ; Marcenò, Corrado ; Martynenko, Vassiliy ; Mencuccini, Maurizio ; Minden, Vanessa ; Moeslund, Jesper Erenskjold ; Moretti, Marco ; Müller, Jonas V. ; Munzinger, Jérôme ; Niinemets, Ülo ; Nobis, Marcin ; Noroozi, Jalil ; Nowak, Arkadiusz ; Onyshchenko, Viktor ; Overbeck, Gerhard E. ; Ozinga, Wim A. ; Pauchard, Anibal ; Pedashenko, Hristo ; Peñuelas, Josep ; Pérez-Haase, Aaron ; Peterka, Tomáš ; Petřík, Petr ; Phillips, Oliver L. ; Prokhorov, Vadim ; Rašomavičius, Valerijus ; Revermann, Rasmus ; Rodwell, John ; Ruprecht, Eszter ; Rūsiņa, Solvita ; Samimi, Cyrus ; Schaminée, Joop H.J. ; Schmiedel, Ute ; Šibík, Jozef ; Šilc, Urban ; Škvorc, Željko ; Smyth, Anita ; Sop, Tenekwetche ; Sopotlieva, Desislava ; Sparrow, Ben ; Stančić, Zvjezdana ; Svenning, Jens Christian ; Swacha, Grzegorz ; Tang, Zhiyao ; Tsiripidis, Ioannis ; Turtureanu, Pavel Dan ; Uğurlu, Emin ; Uogintas, Domas ; Valachovič, Milan ; Vanselow, Kim André ; Vashenyak, Yulia ; Vassilev, Kiril ; Vélez-Martin, Eduardo ; Venanzoni, Roberto ; Vibrans, Alexander Christian ; Violle, Cyrille ; Virtanen, Risto ; Wehrden, Henrik von; Wagner, Viktoria ; Walker, Donald A. ; Wana, Desalegn ; Weiher, Evan ; Wesche, Karsten ; Whitfeld, Timothy ; Willner, Wolfgang ; Wiser, Susan ; Wohlgemuth, Thomas ; Yamalov, Sergey ; Zizka, Georg ; Zverev, Andrei - \ 2019
Journal of Vegetation Science 30 (2019)2. - ISSN 1100-9233 - p. 161 - 186.
biodiversity - community ecology - ecoinformatics - functional diversity - global scale - macroecology - phylogenetic diversity - plot database - sPlot - taxonomic diversity - vascular plant - vegetation relevé
Aims: Vegetation-plot records provide information on the presence and cover or abundance of plants co-occurring in the same community. Vegetation-plot data are spread across research groups, environmental agencies and biodiversity research centers and, thus, are rarely accessible at continental or global scales. Here we present the sPlot database, which collates vegetation plots worldwide to allow for the exploration of global patterns in taxonomic, functional and phylogenetic diversity at the plant community level. Results: sPlot version 2.1 contains records from 1,121,244 vegetation plots, which comprise 23,586,216 records of plant species and their relative cover or abundance in plots collected worldwide between 1885 and 2015. We complemented the information for each plot by retrieving climate and soil conditions and the biogeographic context (e.g., biomes) from external sources, and by calculating community-weighted means and variances of traits using gap-filled data from the global plant trait database TRY. Moreover, we created a phylogenetic tree for 50,167 out of the 54,519 species identified in the plots. We present the first maps of global patterns of community richness and community-weighted means of key traits. Conclusions: The availability of vegetation plot data in sPlot offers new avenues for vegetation analysis at the global scale.
Taxonomy of the order Bunyavirales : second update 2018
Maes, Piet ; Adkins, Scott ; Alkhovsky, Sergey V. ; Avšič-Županc, Tatjana ; Ballinger, Matthew J. ; Bente, Dennis A. ; Beer, Martin ; Bergeron, Éric ; Blair, Carol D. ; Briese, Thomas ; Buchmeier, Michael J. ; Burt, Felicity J. ; Calisher, Charles H. ; Charrel, Rémi N. ; Choi, Il Ryong ; Clegg, J.C.S. ; Torre, Juan Carlos de la; Lamballerie, Xavier de; DeRisi, Joseph L. ; Digiaro, Michele ; Drebot, Mike ; Ebihara, Hideki ; Elbeaino, Toufic ; Ergünay, Koray ; Fulhorst, Charles F. ; Garrison, Aura R. ; Gāo, George Fú ; Gonzalez, Jean Paul J. ; Groschup, Martin H. ; Günther, Stephan ; Haenni, Anne Lise ; Hall, Roy A. ; Hewson, Roger ; Hughes, Holly R. ; Jain, Rakesh K. ; Jonson, Miranda Gilda ; Junglen, Sandra ; Klempa, Boris ; Klingström, Jonas ; Kormelink, Richard ; Lambert, Amy J. ; Langevin, Stanley A. ; Lukashevich, Igor S. ; Marklewitz, Marco ; Martelli, Giovanni P. ; Mielke-Ehret, Nicole ; Mirazimi, Ali ; Mühlbach, Hans Peter ; Naidu, Rayapati ; Zhang, Yong Zhen - \ 2019
Archives of Virology 164 (2019)3. - ISSN 0304-8608 - p. 927 - 941.
In October 2018, the order Bunyavirales was amended by inclusion of the family Arenaviridae, abolishment of three families, creation of three new families, 19 new genera, and 14 new species, and renaming of three genera and 22 species. This article presents the updated taxonomy of the order Bunyavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV).
Precision phenotyping as a tool to automatically monitor health and welfare of individual animals housed in groups
Rodenburg, T.B. - \ 2018
In: Proceedings of the 52nd Congress of the International Society for Applied Ethology. - Wageningen, The Netherlands : Wageningen Academic Publishers - ISBN 9789086863228 - p. 134 - 134.
Farm animals are increasingly housed in large group housing systems. Monitoring health and welfare in these large groups can be challenging. In current welfare assessment schemes, attention for animal-based welfare indicators is increasing, resulting in a shi in focus from environment-based to animal-based indicators. However, in group settings monitoring these animal-based welfare indicators is challenging, especially at the level of the individual animal. Focusing on the individual level is relevant in many dierent settings, e.g. for precision feeding and management, or targeted veterinary care. Also, in the context of animal breeding, focus on the individual level is pivotal; this is frequently done by housing animals of potential interest for selection individually to measure (or evaluate) their phenotypes. In this way, however, no information about the performance of the individual in a group setting can be included in the breeding program, while social interactions can have profound eects on group performance. New genetic methodology now allows the modelling of these social interactions using direct and indirect genetic eects models. is type of methodology can for instance provide information on the propensity of an animal to become a victim of damaging behaviour (direct genetic eect), but also on the propensity to perform damaging behaviour (indirect genetic eect). To utilise this methodology, the ability to measure accurate individual phenotypes in a group setting becomes very important. Breeding companies currently have a strong interest in developing methods for precision phenotyping, relying on new technology that enables tracking of individuals using combinations of dierent sensors. is should allow the use of group housing in future breeding operations and should allow more accurate phenotyping. In the PhenoLab project, we investigated possibilities for tracking of location, activity and proximity of individual laying hens. To meet that aim, we tracked individual hens during a ve-minute Open Field test using two dierent tracking systems: Ultra-wideband tracking using TrackLab and automatic video tracking using EthoVision. Ultra-wideband tracking consists of an active RFID tag that is placed on the bird in a backpack. is tag is then located by triangulation by four beacons. Comparing distance moved between TrackLab and Ethovision yielded 96% similar results (sample of 24 hens). In a second step, the ultra-wideband tracking was also used to measure dierences in activity between high (HFP; n=45) and low (LFP; n=41) feather pecking lines of laying hens. e system was well able to detect the higher activity level in the HFP line compared with the LFP line (10 vs 5 m moving distance), that was also found in previous studies. Interestingly, within the HFP line, birds phenotyped as feather peckers using traditional video observations were found to be the most active individuals compared with the other phenotypes. Precision phenotyping technology could become an important tool to automatically monitor health and welfare of individual animals housed in groups.
Feather pecking phenotype affects behavioural responses of laying hens
Eijk, J.A.J. van der; Lammers, A. ; Rodenburg, T.B. - \ 2018
In: Proceedings of the 52nd Congress of the International Society for Applied Ethology. - Wageningen, The Netherlands : Wageningen Academic Publishers - ISBN 9789086863228 - p. 169 - 169.
Feather pecking (FP) is a major welfare and economic issue in the egg production industry. It involves hens pecking and pulling at feathers of conspecics, thereby negatively aecting welfare. Behavioural characteristics, such as fearfulness, have been related to FP. Although many studies have identied dierences in fearfulness between lines that dier in FP, the relationship between actual FP behaviour (i.e. FP phenotypes) and fearfulness is not well understood. erefore, we compared responses of birds with diering FP phenotypes to several behavioural tests at young and adult ages. We used birds from a genetic line selected for high feather pecking. FP phenotypes of individual birds were identied via FP observations at 3-4, 12-13, 15-16 and 28-29 weeks of age. e total number of severe feather pecks (SFP) given and received over two subsequent weeks was used to categorize birds as feather peckers (P, SFP given >1), feather pecker-victims (P-V, SFP given and received >1), victims (V, SFP received >1) or neutrals (N, SFP given and received 0 or 1) at each age point. Birds were tested individually in a novel environment (NE) test at 4 weeks of age, an open eld (OF) test at 15 weeks of age and a tonic immobility (TI) test at 13 and 28 weeks of age. Experimenters were blinded to the phenotypes. Data were analysed using linear mixed models, with phenotype and batch as xed factors and pen as a random factor. Test time was added as a xed eect for the NE and OF test. Experimenter was added as a xed eect for the NE and TI test. Testing order was included as a xed eect for the TI test. Phenotype eects were tested for each behavioural test and age separately using the most recent FP phenotype categorization. FP phenotype aected the number of ight attempts (F3, 119=3.18, P<0.05) during the NE test, where victims showed more ight attempts compared to neutrals (V=2.3 vs n=1.6; P<0.05) and tended to show fewer ight attempts compared to feather peckers (V=2.3 vs P=2.7; P<0.1). FP phenotype further tended to aect step frequency (F3, 75=2.64, P<0.1) during the OF test, where feather peckers tended to walk more compared to neutrals (P=24.6 vs n=15.7; P<0.1). No FP phenotype eects were found for the TI test. Feather peckers tended to show more active responses (i.e. tended to show more ight attempts compared to victims and tended to walk more compared to neutrals), which could suggest lower fearfulness, compared to victims at 4 weeks of age and compared to neutrals at 15 weeks of age. ese ndings give rst indications that FP phenotypes seem to dier in fearfulness. It should be noted that we only found dierences in the NE and OF test, where behavioural responses could also be related to activity or coping style. Further research is needed to identify whether FP phenotypes dier in activity and whether they can be classied into dierent coping styles.
Effects of (a switch in) enriched vs barren housing on the response to reward loss in pigs in a negative contrast test
Luo, Lu ; Reimert, I. ; Smeets, Sharine ; Haas, E.N. de; Parmentier, H.K. ; Kemp, B. ; Bolhuis, J.E. - \ 2018
In: Proceedings of the 52nd Congress of the International Society for Applied Ethology. - Wageningen, The Netherlands : Wageningen Academic Publishers - ISBN 9789086863228 - p. 233 - 233.
Several studies suggest that animals in a negative emotional state are more sensitive to reward losses as shown by behavioural and neurophysiological responses. In a successive negative contrast (SNC) test, reward losses are induced by decreasing the size of the reward for a task for which animals have been trained. is SNC paradigm has not been widely used in pigs. It is well known that environmental enrichment positively inuences the welfare of pigs, and may induce a more optimistic emotional state, which could reduce their sensitivity to reward losses. We studied pigs in barren (B) or enriched (E) housing, experiencing either a switch in housing conditions at 7 weeks of age or not (4 treatment groups: EE, EB, BE, BB, n=8 pens per group) in an SNC runway task. We hypothesized that B housed pigs, particularly those that changed from E to B housing, would show an enhanced sensitivity to reward losses. One pig per pen was trained to run a 24.6 m U-shaped runway for 6 pieces and one for 1 piece of apple. Each pig received 3 trials per day, with a maximum of 120 sec/trial. Latency to start eating the reward was recorded, and the average was calculated per day. Aer 11 days, all pigs received 1 piece of apple only for another 11 days (reward shi: 6-1 vs 1-1 reward group), i.e. the group originally receiving 6 pieces of apple experienced a reward loss. Eects of pre-housing, post-housing, (original) reward size, day and interactions were analysed using mixed models with a random eect of animal. Fiy-one pigs were successfully trained. Before the reward shi, over the rst 11 days, pre-housing × post-housing × reward size aected the average run-time (P<0.05). All BB pigs ran slower than other pigs (BB: 59.3±2.8; BE: 35.9±1.7; EB: 39.6±2.2; EE: 40.9±2.2, P<0.05), without any other signicant pairwise dierences. Analysis per treatment revealed, however, that EB 6-reward pigs were faster than the 1-reward pigs. Overall latency was higher on the last days (P<0.001). Aer the reward size shied to 1 on day 12, pre-housing × post-housing aected the latency (P<0.001). Post hoc analysis showed that again, BB pigs were slower than other pigs (BB: 88.2±2.7; BE 62.3±2.3; EB: 57.3±2.3; EE: 70.4±2.6, P<0.001), and EB pigs were faster than EE pigs (P<0.05). Pigs ran slower aer than before the reward shi (P<0.001). Nevertheless, pigs in the 6-1 group ran slower than pigs in the 1-1 group aer the reward shi (6-1: 73.9±2.0; 1-1: 66.4±1.8, P<0.05), suggesting that pigs are sensitive to a loss in reward size. is was, however, irrespective of housing given the lack of interactions with reward size. We conclude that housing aected the latency to run down a runway for a reward in pigs, which can indicate a lower motivation in the BB pigs, an eect that was absent in the B pigs that switched to enriched housing (BE pigs). We found, however, no evidence that housing or a switch in housing conditions aected the sensitivity to reward loss.
|Foams (chapter 7)
Bergeron, V. ; Walstra, P. - \ 2005
In: Fundamentals of interface and colloid science, volume V Soft Colloids Elsevier Academic Press - ISBN 9780124605299 - 38 p.
Adsorption of nonionic surfactants onto polystyrene : kinetics and reversibility
Geffroy, C. ; Cohen Stuart, M.A. ; Wong, K. ; Cabane, B. ; Bergeron, V. - \ 2000
Langmuir 16 (2000). - ISSN 0743-7463 - p. 6422 - 6430.
The reversible adsorption and desorption kinetics of nonionic surfactants at a hydrophobic surface have been studied by reflectometry. This enables the measurement of the adsorption isotherm with unprecedented accuracy. It is shown that the adsorption mechanism can be split into three processes. The surface is first covered by single monomers that experience a strong hydrophobic interaction. This is followed by a typically cooperative process leading to the formation of surface aggregates. At the saturation level, the surfactant molecules stagger in the interface such that there is a possible overlap of hydrophilic headgroups with hydrophobic tails. All this information comes directly out of the kinetics that can be modeled in terms of a local equilibrium.
Thyroid hormone binding proteins as novel targets for hydroxylated polyhalogenated aromatic hydrocarbons (PHAHs) : possible implications for toxicity
Lans, M.C. - \ 1995
Agricultural University. Promotor(en): J.H. Koeman; A. Brouwer. - S.l. : Lans - ISBN 9789054854302 - 152
polychloorbifenylen - dioxinen - pentachloorfenol - organische halogeenverbindingen - gehalogeneerde koolwaterstoffen - schildklierhormonen - polychlorinated biphenyls - dioxins - pentachlorophenol - organic halogen compounds - halogenated hydrocarbons - thyroid hormones
Some toxic effects caused by polyhalogenated aromatic hydrocarbons (PHAHs) develop through alterations in the reproductive and thyroid hormone regulatory systems, thereby affecting (brain) development, reproduction and behaviour of several species (Stone, 1995, Birnbaum, 1994, for review: Brouwer et al. , 1995, Peterson et al. , 1993). In this thesis we have focused on the effects of different classes of PHAHs, eg. polychlorinated biphenyls (PCBs), dibenzofurans (PCDFs) and dibenzo- p -dioxins (PCDDs) and their hydroxylated metabolites on thyroid hormone homeostasis. These changes seem to be partly caused by Ah-receptor mediated changes in thyroid hormone glucuronidation, and effects on the thyroid gland affecting hormone production and secretion. However, hydroxylated metabolites of PCBs, PCDFs and PCDDs may have an additional effect on thyroid hormone transport. Previous studies (Brouwer, 1987) have shown that exposure to 3,3',4,4'- tetrachlorobiphenyl (TCB) can disturb the plasma transport of thyroxine (T 4 ) and retinol in rats through specific competition of a hydroxylated metabolite, 4-OH-3,3',4',5-tetraCB, with T 4 for the thyroid hormone binding site of transthyretin (TTR), the major thyroid hormone transport protein in rodents. This observation raised the question if structurally related hydroxylated PHAH- metabolites could interact with TTR in the same way, as well as with other thyroxine binding proteins, like thyroxine binding globulin (TBG) and type-1-deiodinase (ID-1), subsequently disturbing thyroid hormone transport and metabolism. Special attention was also paid on the structure-activity relationships of hydroxylated PHAH metabolites for binding to TTR by using in vitro and in vivo studies and X-ray crystallographic structure analysis,
In vitro studies on interactions of hydroxylated PHAH metabolites with thyroxine binding proteins
In in vitro studies the interactions of several hydroxylated PHAH metabolites with 3 different T 4 binding proteins, eg. TTR, thyroxine binding globulin (TBG) and type-1-deiodinase (ID-1), were investigated (Chapter 2, 3 and 4). The inhibition of T 4 binding to TTR by hydroxylated PHAH metabolites was studied using in vitro T 4 -TTR bindingstudies. These studies revealed the structural requirements for competition of T 4 binding to TTR by hydroxylated PHAH metabolites: para- or meta-hydroxylation on one or both phenylrings, with one or more adjacent chlorine substitutions (Chapter 2). PHAH metabolites with these structural characteristics showed a remarkable resemblance to T 4 the natural ligand for TTR, consequently displacing T 4 from the T 4 binding site of TTR. Both non-planar, ortho-chlorinated hydroxylated PCB metabolites and rigid, planar hydroxylated PCDF or PCDD metabolites could inhibit T 4 -TTR binding. However, the ortho-hydroxylated PHAH metabolites and parent PHAH compounds, like TCDD, 2,3,3',4,4'-pentaCB and 3,3',4,4'-tetraCB could not inhibit T 4 -TTR binding in vitro.
In subsequent in vitro studies, a wide range of hydroxylated PHAH metabolites did not inhibit T 4 binding to TBG, the major plasma thyroid hormone transport protein in man (Chapter 3). This indicates that ligand interactions with TTR or TBG are clearly different. Additional studies with iodothyronine derivatives, showed that tri-iodophenol and to a lesser extent di-iodotyrosine could inhibit T 4 -TTR binding but not T 4 -TBG binding in vitro. Finally, the enzymatic activity of hepatic ID-1, which plays a role in the (in)activation of thyroid hormones, could be competitively inhibited mainly by di-para-hydroxylated, meta-halogenated PHAH metabolites while mono-hydroxylated PHAH metabolites were 10 to 100 times less potent (Chapter 4). The differences between the structural requirements of hydroxylated PHAH metabolites for interactions with TTR, TBG and ID-1, are in line with previous studies in which related hydroxylated PHAH compounds or iodothyronine derivatives were used. In conclusion, specific hydroxylated PHAH metabolites can disturb T4-TTR interactions, or inhibit ID-1 activity in vitro, indicating that hydroxylated PHAH metabolites may play an additional role in the observed disturbances in thyroid hormone transport and metabolism after PHAH exposure in vivo .
In vivo studies on effects of Aroclor 1254 and TCDD on thyroid hormone transport and metabolism
Two in vivo experiments were carried out to study role that both disturbances in plasma T 4 transport and hepatic T 4 metabolism caused by hydroxylated PHAH metabolites play in the observed decreases in plasma T 4 levels. Rats were exposed to Aroclor 1254, a commercial mixture containing persistent and metabolisable PCB congeners (Chapter 5) or the persistent 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) (Chapter 6).
In adult Wistar rats, that were exposed to a high dose of Aroclor 1254, plasma T 4 levels were decreased on day 3 and day 8 (Chapter 5). In addition, high levels of a single hydroxylated PCB metabolite, eg. 4-OH-2,3,3',4',5-pentaCB, were detected in plasma of the rats on day 8, while lower concentrations of this metabolite were present in the blood on day 3. However, the T 4 binding capacity in plasma was decreased only in the high dosed group on day 8 but not on day 3, indicating a threshold level for the hydroxylated PCB metabolite to disturb T 4 -TTR binding. On both day 3 and 8, hepatic cytochrome P450 1A1 levels and activity were induced, which is essential for the formation of hydroxylated metabolites. Hepatic T 4 glucuronidation was induced simultaneously. The decreased plasma T 4 levels found in all exposure groups could therefore be attributed to both disturbed plasma T 4 transport and/or induced T 4 glucuronidation. No significant changes in plasma T 3 levels were found following Aroclor 1254 treatment. In addition, hepatic ID-1 activity was not decreased, suggesting that the in vitro inhibition by hydroxylated PCB metabolites does not occur in vivo. However in an earlier study Adams et al. (1990), in vivo exposure to the easily metabolisable 3,3',4,4'-tetraCB or persistent TCDD could inhibit ID-1 activity. The levels of PCB metabolites with the required structure for inhibition of hepatic ID-1 activity were possibly too low (Chapter 4) liver after Aroclor 1254 exposure in vivo.
Another remarkable finding was the selective retention of a single specific hydroxylated PCB metabolite, 4-OH-2,3,3',4',5-pentaCB, in plasma of rats exposed to a complex mixture of PCB congeners (Fig. 1). This was the result of the presence of PCB-congeners that strongly induce cytochrome P4501AI activity and PCB-congeners that could easily form hydroxylated PCB metabolites in the Aroclor 1254 mixture, and the strict selectivity of the TTR present in plasma retaining only hydroxylated PCB metabolites that meet the structural requirements as described in Chapter 2. Surprisingly the 4-OH- 2,3,3',4',5-pentaCB metabolite which was formed and selectively retained in plasma, has a hydroxy group on the highest chlorinated ring, in contrast to the expected formation of mainly metabolites with a para - or meta -hydroxy group on the least chlorinated ring. However, the inhibition potencies of T 4 -TTR binding for the 4-OH-2,3,3',4',5-pentaCB metabolite (Chapter 5) and the structurally related 4'-OH-2,3,3',4,5'-pentaCB metabolite (Chapter 2) were almost similar. There is no clear indication yet on the mechanism of selective retention of the 4-OH-2,3,3',4',5-pentaCB in rat plasma, although pharmacokinetics and tissue levels of the presumed parent compounds 2,3,3',4,4'- pentaCB (CB 105) or 2,3',4,4',5-pentaCB (CB 118) may play a role.
No detectable levels of hydroxylated metabolites were found by GC-MS analysis of plasma extracts of rats at both day 3 and 8 following exposure to the persistent TCDD, although cytochrome P4501A1 levels and activity were markedly induced (Chapter 6). In addition no unequivocal decrease in T 4 -TTR binding in plasma of TCDD-exposed rats was observed. However, hepatic thyroid hormone metabolism was clearly altered: T 4 glucuronidation and brain type-2-deiodinase (ID-2) activity were increased and hepatic ID-1 activity was decreased, which may explain the observed plasma T4 reductions in the TCDD exposed rats. These changes in thyroid hormone homeostasis suggest a hypothyroxinemic state of the TCDD-exposed rats, although no decreased plasma T4 levels were found. The decrease in ID-1 activity after TCDD exposure was not likely to be caused by hydroxylated metabolites, as was described in Chapter 4, but may be caused by direct effects of TCDD on ID-1 activity or by the assumed hypothyroid state of the TCDD exposed rats.
While Aroclor 1254 exposure disturbed T4 plasma transport and increase T 4 glucuronidation (Chapter 5), TCDD exposure only enhanced the hepatic elimination of T4 (Chapter 6), leading to decreased plasma T 4 levels. Although the in vivo studies described in this thesis indicate two different mechanisms for decreases in plasma T 4 levels after PHAH exposure, we can not exclude a third possible mechanism since several studies described changes on thyroid gland histology and thyroid hormone secretion after exposure to Aroclor 1254, TCDD and related compounds.
Structural basis for interactions of hydroxy-PCB metabolites with TTR
The selective retention of a specific hydroxylated PCB metabolite in vivo (Chapter 5), inspired us to look into the interactions of hydroxylated PCB metabolites with TTR in more detail, and to try to find a structural basis for the structural requirements for TTR binding as described in Chapter 2. X-ray crystallographic analysis of a complex of TTR with a hydroxylated PCB metabolite, eg. 4,4'- (OH) 2 -3,3',5,5'-tetraCB, refined to a 2.7 A resolution, revealed a hydrogen bond formation between a para-hydroxy group of the metabolite with the paired Serine 117 amino acid residues, present in the centre of the TTR binding channel (Chapter 7). The location of this hydroxylated PCB metabolite, deep in the binding channel, and the hydrogen bond formation could explain the stronger TTR binding affinity of this metabolite than the natural ligand T 4 . The chlorine atoms present on the meta-positions of the 4,4'-(OH) 2 -3,3',5,5'-tetraCB, metabolite, fitted easily in the T 4 -iodine binding pockets present in the TTR binding channel. Additional computer-assisted graphics modelling studies on the interactions of several hydroxylated PCB metabolites with TTR, showed that hydroxy groups present on meta-positions could also form hydrogen bonds with the paired Serine 117 residues in the centre of the binding channel (Chapter 7). Furthermore, the modelling studies showed no significant differences between the interactions of hydroxylated PCB metabolites and the structurally related pentachlorophenol (PCP) with TTR, although in vivo studies by others indicated the disruption of the complex of retinol binding protein (RBP) and TTR after binding of a hydroxylated PCB metabolite but not by PCP in rodents. In conclusion, the detailed structural studies described in Chapter 7 confirmed the necessity of para- or meta- hydroxylation and adjacent chlorine substituents as structural elements of hydroxylated metabolites of PCBs and related compounds for interactions with TTR (Chapter 2), leading to selective retention of a specific hydroxylated PCB metabolite in plasma of rats exposed to a complex PCB mixture in vivo (Chapter 5).
The outcome of the present study clearly reveals the structural requirements that are essential for interactions of PHAH metabolites and other related chemicals for interactions with TTR. Hydroxylated PHAH metabolites can structurally resemble the thyroid hormone T 4 Overall the structural requirements for TTR interaction were hydroxysubstitution on the para - or meta positions of one or both of the phenyl rings, with adjacent chlorine substitutions, herewith confirming some of the suggestions for TTR interactions of related hydroxylated PHAH metabolites by Rickenbacher et al . (1986). Especially the observation by X-ray crystallographic structure analysis that a hydrogen bond could be formed in the TTR binding channel upon binding of a hydroxylated PCB metabolite, provides strong evidence that para - or meta -hydroxylation of the PHAH compound forms an essential prerequisite for binding to the T4 binding site of TTR. No interactions with TTR were found for the tested parent PHAH compounds, contradictory to earlier suggestions of McKinney et al. (1985) which were based mainly on computer modelling and few in vitro binding studies (Rickenbacher et al , 1986). It should be noted that graphics modelling may show that parent PHAH compounds may fit the TTR binding site, but gives little information on binding affinity to TTR. In an affirmative in vitro T 4 -TTR binding assay, several parent PCB congeners (3,3',4,4'-tetraCB, 3,3',4,4',5-pentaCB, 3,3',4,4',5,5'-hexaCB, 2,3,3',4,4'-pentaCB, 2,2',5,5'- tetraCB), TCDD and Aroclor 1254, a commercial PCB mixture, were tested at high concentrations and exhibited no inhibition of T 4 -TTR binding (unpublished data).
PHAH metabolites that are predicted to have high binding affinities for TTR are indeed detected in plasma of rodents experimentally exposed to PCBs or PCDFs (Morse et al ., 1995b, Koga et al ., 1990, Kuroki et al. , 1993). For instance, exposure to a complex mixture of PCBs, Aroclor 1254, led to the selective retention in blood of a single PCB metabolite, 4-OH-2,3,3',4',5- pentaCB, which met the structural requirements for TTR binding (Bergman et al ., 1994).
On the basis of the proposed structural requirements we can give an explanation for the interactions of related compounds with TTR as found by others, for instance pentachlorophenol (Van den Berg, 1990, Van Raay et al ., 1994, Den Besten et al ., 1991), natural compounds like flavones and halogenated aurones (Cody, 1989; Ciszak et al ., 1992) and certain drugs like milrinone (Wojtczak et al. , 1993). Moreover, these structural insights make it possible to predict whether other related classes of environmental contaminants can interact with TTR. In addition, due to combined exposure in the environment, one may expect additivity of binding to TTR of hydroxylated PHAH metabolites with other structurally related environmental or natural compounds.
An important question is whether these experimental data can be extrapolated to other species. Two factors are essential for the TTR mediated selective retention of hydroxylated PHAH metabolites namely the presence of TTR in blood and the formation of relevant PHAH metabolites. It is most likely that hydroxylated. metabolites can be formed in many species other than rodent. Recently hydroxylated PCB metabolites were identified in human and seal plasma, which were environmentally exposed to background PCB levels (Bergman et al. , 1994). The major metabolites were again the 4-OH-2,3,3',4',5-pentaCB metabolite and to a lesser extent 4-OH-2',3,3',4',5-pentaCB in seal and human plasma and 4-OH-2,2',3,4',5,5',6-heptaCB in human plasma. Thus the hydroxylated PCB metabolites detected in vivo completely matched the structural requirements for TTR binding. The PHAH metabolite patterns in plasma of both experimentally and environmentally exposed animals and humans are species specific and depend not only on the structural requirements for binding to TTR, but also on the exposure situation and the capacity of biotransformation of PHAHs of the species.
The species-specific metabolism of PHAHs decreases in the order: terrestrial mammals>aquatic mammals>birds>fish (Safe, 1989). Several mammalian and avian species, like rats, seals, porpoises and eiderducks could form hydroxylated metabolites in in vitro microsomal incubations with the model substrate 3,3',4,4'-tetraCB (TCB). However fish, like trout and flounder, could not metabolise TCB, although cytochrome P4501A-like activity, responsible for biotransformation of planar PHAHs, can be induced (Murk et al., 1994, Morse et al., 1995c, Ishida et al., 1991).
The selective retention of specific hydroxylated PHAH metabolites in plasma through binding to TTR is expected in species that both can metabolise PHAHs and posses TTR as a plasma thyroid hormone binding protein. TTR is a evolutionary conservative protein present in plasma of not only rodents but also other placental mammals, birds and to a lesser extent in reptiles. No TTR was detected in the lower species like fish and amphibians. In higher mammals like man, however, not only TTR but also thyroxine binding globulin (TBG), is present in blood as a primary thyroid hormone transport protein. In conclusion, hydroxylated PHAH metabolites can be formed and selectively retained by TTR in blood of a wide variety of species.
The toxicological consequences of the TTR mediated selective retention of hydroxylated PHAH metabolites in plasma are not yet fully understood. The TTR protein plays a primary role in the transport of thyroid hormones in the blood of many species. Although TTR binds less T 4 than TBG in human serum, TTR may be responsible for much of the immediate delivery of T 4 and T 3 to cells due to the lower binding T 4 affinity. Furthermore TTR is important for the transport of retinol in blood by forming a complex with retinol-binding protein (Robbins, 1991).
Disturbances in thyroid hormone plasma levels are found in several species experimentally or environmentally exposed to PHAHs, like rodents, seal (Brouwer et al., 1989) and man (Koopman Esseboom et al., 1994), species in which hydroxylated PCB metabolites were also present in plasma. Disruption of thyroid hormone homeostasis after exposure to PHAHs can however be caused by at least two mechanisms, eg. the disturbed plasma T 4 transport through competitive binding of hydroxylated PHAH metabolites to TTR, but also the Ah-receptor mediated induction of T 4 glucuronidation by parent compounds.
The possible disruption of the TTR-RBP complex upon binding of a hydroxylated PHAH metabolite can also markedly decrease plasma retinol levels in rodents (Brouwer, 1987). It was suggested that seals exposed to PHAHs in the environment, have an impaired function of the immune system (de Swart, 1995), possibly resulting from disturbed retinoid levels (Brouwer, 1991, Brouwer et al. 1989). Hydroxylated PHAH metabolites may attribute to these effects on thyroid hormone and retinoid homeostasis through interactions with TTR in plasma. It is not known whether similar effects occur in man.
TTR is the major thyroid hormone binding protein in cerebro-spinal fluid (CSF), suggesting a role in distribution of thyroid hormones in the central nervous system. This TTR is produced in the choroid plexus and is present in high concentrations in CSF of rats and humans, even at a very early stage in development. Moreover, in all species where TTR is present in blood, TTR has also been detected in brain. Because TTR is an important carrier for T 4 to target tissues, for instance brain, one may expect that it may also act as a facilitated transport system for hydroxylated PHAH metabolites. This is in accordance with observations of a strong accumulation of hydroxylated PCB metabolites of maternal origin in the plasma and brain of late gestational fetuses from pregnant rats or mice exposed to PCBs (Morse et al., 1995b,d, Darnerud et al., 1995). In rat fetuses perinatally exposed to Aroclor 1254 the selective accumulation of the 4-OH-2,3,3',4',5-pentaCB metabolite in maternal plasma and fetal plasma and brain led to decreases in brain T 4 levels, while brain T 3 levels were only lightly changed. In addition plasma and hepatic retinoid concentrations were decreased in fetal and neonatal offspring (Morse et al., 1995a). The hydroxylated metabolites accumulated to high levels in fetal rat brain and may themselves attributeto observed neurochemical changes (Morse, 1995).
Hydroxylated PHAH metabolites have been shown to possess biological activity in vitro (Brouwer, 1994). Hydroxylated PCB metabolites can interfere with mitochondrial structure and function in vivo and in vitro (Lans et al., 1990, Narashimhan et al., 1991). Moreover, they can bind to the Ah-receptor and weakly induce EROD activity. In addition, an in vitro marker of tumor promoting potential, the gap-junctional intercellular communication, could be weakly inhibited. Hydroxylated PCB metabolites can also exert (anti)-estrogenic activities in vivo (Bergeron et al., 1994) and in vitro (Kramer et al., 1994). No clear structure activity relationships for (anti)- estrogenicity could be found for the tested hydroxylated PCB metabolites. However, the hydroxylated PCB metabolites selectively retained in fetal plasma and brain (Morse et al., 1995d) do have a weak (anti)-estrogenic activity. The intrinsic capacity to disrupt endocrine systems, eg. thyroid and estrogen status, and the relatively large accumulating levels of hydroxylated PCB metabolites in late gestational rat fetuses, suggests there is a potential risk for adverse developmental effects by these hydroxylated PHAHs. This possible hydroxy PCBmediated route of developmental toxicity should be investigated in a sound in vivo experimental setup.
Subtle changes in plasma thyroid hormone levels and parameters for neurological development were described in children exposed to background levels of PHAHs in utero and through lactation (Koopman-Esseboom et al., 1994, Sauer et al., 1994, Pluim et al., 1993). Hydroxylated PHAH metabolites did not interact with TBG, the major T 4 binding protein in human plasma (Lans et al., 1994). However, the hydroxylated PCB metabolites which are recently detected in human plasma (Bergman et al., 1994) are mainly bound to TTR, as was found after selective purification of TTR from human plasma (unpublished results). Therefore TTR-mediated accumulation of hydroxylated PCB metabolites or related compounds in fetal plasma and brain and subsequent decreases in T 4 levels, as found in late gestational rat fetuses, may be of concern for fetal growth and (brain) development in a wide variety of species, including man.