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Bauer, Michael ; Glenn, Tasha ; Achtyes, Eric D. ; Agaoglu, Esen ; Altınbaş, Kürşat ; Andreassen, Ole A. ; Angelopoulos, Elias ; Ardau, Raffaella ; Arrua Vares, Edgar ; Aydin, Memduha ; Ayhan, Yavuz ; Baethge, Christopher Jan ; Bauer, Rita ; Baune, Bernhard T. ; Balaban, Ceylan ; Becerra-Palars, Claudia ; Behere, Aniruddh P. ; Behere, Prakash B. ; Belete, Habte ; Belete, Tilahun ; Belizario, Gabriel Okawa ; Bellivier, Frank ; Belmaker, Robert H. ; Benedetti, Francesco ; Berk, Michael ; Bersudsky, Yuly ; Bicakci, Şule ; Birabwa-Oketcho, Harriet ; Bjella, Thomas D. ; Brady, Conan ; Cabrera, Jorge ; Cappucciati, Marco ; Castro, Angela Marianne Paredes ; Chen, Wei-Ling ; Cheung, Eric Y. Wo ; Chiesa, Silvia ; Crowe, Marie ; Cuomo, Alessandro ; Dallaspezia, Sara ; Del Zompo, Maria ; Desai, Pratikkumar ; Dodd, Seetal ; Donix, Markus ; Etain, Bruno ; Fagiolini, Andrea ; Fellendorf, Frederike Tabea ; Ferensztajn-Rochowiak, Ewa ; Fiedorowicz, Jess G. ; Fountoulakis, Kostas N. ; Frye, Mark A. ; Geoffroy, Pierre A. ; Gonzalez-Pinto, Ana ; Gottlieb, John F. ; Grof, Paul ; Haarman, Bartholomeus C. M. ; Harima, Hirohiko ; Hasse-Sousa, Mathias ; Henry, Chantal ; Høffding, Lone ; Houenou, Josselin ; Imbesi, Massimiliano ; Isometsä, Erkki T. ; Ivkovic, Maja ; Janno, Sven ; Johnsen, Simon ; Kapczinski, Flávio ; Karakatsoulis, Gregory N. ; Kardell, Mathias ; Kessing, Lars Vedel ; Kim, Seong Jae ; König, Barbara ; Kot, Timur L. ; Koval, Michael ; Kunz, Mauricio ; Lafer, Beny ; Landén, Mikael ; Larsen, Erik R. ; Lenger, Melanie ; Lewitzka, Ute ; Licht, Rasmus W. ; Lopez-Jaramillo, Carlos ; MacKenzie, Alan ; Madsen, Helle Østergaard ; Madsen, Simone Alberte Kongstad A. ; Mahadevan, Jayant ; Mahardika, Agustine ; Manchia, Mirko ; Marsh, Wendy ; Martinez-Cengotitabengoa, Monica ; Martiny, Klaus ; Mashima, Yuki ; McLoughlin, Declan M. ; Meesters, Ybe ; Melle, Ingrid ; Meza-Urzúa, Fátima ; Ming, Mok Yee ; Monteith, Scott ; Moorthy, Muthukumaran ; Morken, Gunnar ; Mosca, Enrica ; Mozzhegorov, Anton A. ; Munoz, Rodrigo ; Mythri, Starlin V. ; Nacef, Fethi ; Nadella, Ravi K. ; Nakanotani, Takako ; Nielsen, René Ernst ; O'Donovan, Claire ; Omrani, Adel ; Osher, Yamima ; Ouali, Uta ; Pantovic-Stefanovic, Maja ; Pariwatcharakul, Pornjira ; Petite, Joanne ; Pfennig, Andrea ; Pica Ruiz, Yolanda ; Pilhatsch, Maximilian ; Pinna, Marco ; Pompili, Maurizio ; Porter, Richard ; Quiroz, Danilo ; Rabelo-da-Ponte, Francisco Diego ; Ramesar, Raj ; Rasgon, Natalie ; Ratta-apha, Woraphat ; Ratzenhofer, Michaela ; Redahan, Maria ; Reddy, M. S. ; Reif, Andreas ; Reininghaus, Eva Z. ; Richards, Jenny Gringer ; Ritter, Philipp ; Rybakowski, Janusz K. ; Sathyaputri, Leela ; Scippa, Ângela M. ; Simhandl, Christian ; Severus, Emanuel ; Smith, Daniel ; Smith, José ; Stackhouse Jr., Paul W. ; Stein, Dan J. ; Stilwell, Kellen ; Strejilevich, Sergio ; Su, Kuan-Pin ; Subramaniam, Mythily ; Sulaiman, Ahmad Hatim ; Suominen, Kirsi ; Tanra, Andi J. ; Tatebayashi, Yoshitaka ; Teh, Wen Lin ; Tondo, Leonardo ; Torrent, Carla ; Tuinstra, Daniel ; Uchida, Takahito ; Vaaler, Arne E. ; Veeh, Julia ; Vieta, Eduard ; Viswanath, Biju ; Yoldi-Negrete, Maria ; Yalcinkaya, Oguz Kaan ; Young, Allan H. ; Zgueb, Yosra ; Whybrow, Peter C.
Background: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01. Conclusion: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed.
Randall, Joshua C. ; Winkler, Thomas W. ; Kutalik, Zoltán ; I. Berndt, Sonja ; Jackson, Anne U. ; Monda, Keri L. ; Kilpeläinen, Tuomas O. ; Esko, Tõnu ; Mägi, Reedik ; Li, Shengxu ; Workalemahu, Tsegaselassie ; Feitosa, Mary F. ; Croteau-Chonka, Damien C. ; Day, Felix R. ; Fall, Tove ; Ferreira, Teresa ; Gustafsson, Stefan ; Locke, Adam E. ; Mathieson, Iain ; Scherag, André ; Vedantam, Sailaja ; Wood, Andrew R. ; Liang, Liming ; Steinthorsdottir, Valgerdur ; Thorleifsson, Gudmar ; Dermitzakis, Emmanouil T. ; Dimas, Antigone S. ; Karpe, Fredrik ; Min, Josine L. ; Nicholson, George ; Clegg, Deborah J. ; Person, Thomas ; Krohn, Jon P. ; Bauer, Sabrina ; Buechler, Christa ; Eisinger, Kristina ; Bonnefond, Amélie ; Froguel, Philippe ; Hottenga, Jouke-Jan ; Prokopenko, Inga ; Waite, Lindsay L. ; Harris, Tamara B. ; Smith, Albert Vernon ; Shuldiner, Alan R. ; McArdle, Wendy L. ; Caulfield, Mark J. ; Munroe, Patricia B. ; Grönberg, Henrik ; Chen, Yii-Der Ida ; Li, Guo ; Beckmann, Jacques S. ; Johnson, Toby ; Thorsteinsdottir, Unnur ; Teder-Laving, Maris ; Khaw, Kay-Tee ; Wareham, Nicholas J. ; Zhao, Jing Hua ; Amin, Najaf ; Oostra, Ben A. ; Kraja, Aldi T. ; Province, Michael A. ; Cupples, L. Adrienne ; Heard-Costa, Nancy L. ; Kaprio, Jaakko ; Ripatti, Samuli ; Surakka, Ida ; Collins, Francis S. ; Saramies, Jouko ; Tuomilehto, Jaakko ; Jula, Antti ; Salomaa, Veikko ; Erdmann, Jeanette ; Hengstenberg, Christian ; Loley, Christina ; Schunkert, Heribert ; Lamina, Claudia ; Wichmann, Heinz Erich ; Albrecht, Eva ; Gieger, Christian ; Hicks, Andrew A. ; Johansson, Åsa ; Pramstaller, Peter P. ; Kathiresan, Sekar ; Speliotes, Elizabeth K. ; Penninx, Brenda W. J. H. ; Hartikainen, Anna-Liisa ; Jarvelin, Marjo-Riitta ; Gyllensten, Ulf ; Boomsma, Dorret I. ; Campbell, Harry ; Wilson, James F. ; Chanock, Stephen J. ; Farrall, Martin ; Goel, Anuj ; Medina-Gomez, Carolina ; Rivadeneira, Fernando ; Estrada, Karol ; Uitterlinden, André G. ; Hofman, Albert ; Zillikens, M. Carola ; Heijer, Martin den ; Kiemeney, Lambertus Adrianus ; Maschio, Andrea ; Hall, Per ; Tyrer, Jonathan ; Teumer, Alexander ; Völzke, Henry ; Kovacs, Peter ; Tönjes, Anke ; Mangino, Massimo ; Spector, Tim D. ; Hayward, Caroline ; Rudan, Igor ; Hall, Alistair S. ; Samani, Nilesh J. ; Attwood, Antony Paul ; Sambrook, Jennifer G. ; Hung, Joseph ; Palmer, Lyle J. ; Lokki, Marja-Liisa ; Sinisalo, Juha ; Boucher, Gabrielle ; Huikuri, Heikki ; Lorentzon, Mattias ; Ohlsson, Claes ; Eklund, Niina ; Eriksson, Johan G. ; Barlassina, Cristina ; Rivolta, Carlo ; Nolte, Ilja M. ; Snieder, Harold ; Klauw, Melanie M. van der ; Vliet-Ostaptchouk, Jana V. van ; Gejman, Pablo V. ; Shi, Jianxin ; Jacobs, Kevin B. ; Wang, Zhaoming ; Bakker, Stephan J. L. ; Mateo Leach, Irene ; Navis, Gerjan ; Harst, Pim van der ; Martin, Nicholas Gordon ; Medland, Sarah E. ; Montgomery, Grant W. ; Yang, Jian ; Chasman, Daniel I. ; Ridker, Paul M. ; Rose, Lynda M. ; Lehtimäki, Terho ; Raitakari, Olli ; Absher, Devin ; Iribarren, Carlos ; Basart, Hanneke ; Hovingh, Kees G. ; Hyppönen, Elina ; Power, Chris ; Power, Chris ; Anderson, Denise ; Beilby, John P. ; Hui, Jennie ; Jolley, Jennifer ; Sager, Hendrik ; Bornstein, Stefan R. ; Schwarz, Peter E. H. ; Kristiansson, Kati ; Perola, Markus ; Lindström, Jaana ; Swift, Amy J. ; Uusitupa, Matti ; Atalay, Mustafa ; Lakka, Timo A. ; Rauramaa, Rainer ; Bolton, Jennifer L. ; Fowkes, Gerry ; Fraser, Ross M. ; Price, Jackie F. ; Fischer, Krista ; KrjutÅ¡kov, Kaarel ; Metspalu, Andres ; Mihailov, Evelin ; Langenberg, Claudia ; Luan, Jian'an ; Ong, Ken K. ; Chines, Peter S. ; Keinanen-Kiukaanniemi, Sirkka M. ; Saaristo, Timo E. ; Edkins, Sarah ; Franks, Paul W. ; Hallmans, Göran ; Shungin, Dmitry ; Morris, Andrew David ; Palmer, Colin N. A. ; Erbel, Raimund ; Moebus, Susanne ; Nöthen, Markus Maria ; Pechlivanis, Sonali ; Hveem, Kristian ; Narisu, Narisu ; Hamsten, Anders ; Humphries, Steve E. ; Strawbridge, Rona J. ; Tremoli, Elena ; Grallert, Harald ; Thorand, Barbara ; Illig, Thomas ; Koenig, Wolfgang ; Müller-Nurasyid, Martina ; Peters, Annette ; Böhm, Bernhard O. ; Kleber, Marcus E. ; März, Winfried ; Winkelmann, Bernhard R. ; Kuusisto, Johanna ; Laakso, Markku ; Arveiler, Dominique ; Cesana, Giancarlo ; Kuulasmaa, Kari ; Virtamo, Jarmo ; Yarnell, John W. G. ; Kuh, Diana ; Wong, Andrew ; Lind, Lars ; Faire, Ulf de ; Gigante, Bruna ; Magnusson, Patrik K. E. ; Pedersen, Nancy L. ; Dedoussis, George ; Dimitriou, Maria ; Kolovou, Genovefa ; Kanoni, Stavroula ; Stirrups, Kathleen ; Bonnycastle, Lori L. ; Njølstad, Inger ; Wilsgaard, Tom ; Ganna, Andrea ; Rehnberg, Emil ; Hingorani, Aroon ; Kivimaki, Mika ; Kumari, Meena ; Assimes, Themistocles L. ; Barroso, Inês ; Boehnke, Michael ; Borecki, Ingrid B. ; Deloukas, Panos ; Fox, Caroline S. ; Frayling, Timothy ; Groop, Leif C. ; Haritunians, Talin ; Hunter, David ; Ingelsson, Erik ; Kaplan, Robert ; Mohlke, Karen L. ; North, Kari E. ; Lindgren, Cecilia M. ; Qi, Lu ; Loos, Ruth J. F. ; Heid, Iris M. ; Hirschhorn, Joel N. ; McCarthy, Mark I. ; Abecasis, Gonçalo R. ; Stefansson, Kari ; Strachan, David P. ; Schlessinger, David ; O'Connell, Jeffrey R. ; Duijn, Cornelia M. van
Men and women differ substantially regarding height, weight, and body fat. Interestingly, previous work detecting genetic effects for waist-to-hip ratio, to assess body fat distribution, has found that many of these showed sex-differences. However, systematic searches for sex-differences in genetic effects have not yet been conducted. Therefore, we undertook a genome-wide search for sexually dimorphic genetic effects for anthropometric traits including 133,723 individuals in a large meta-analysis and followed promising variants in further 137,052 individuals, including a total of 94 studies. We identified seven loci with significant sex-difference including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were significant in women, but not in men. Of interest is that sex-difference was only observed for waist phenotypes, but not for height or body-mass-index. We found no evidence for sex-differences with opposite effect direction for men and women. The PPARG locus is of specific interest due to its link to diabetes genetics and therapy. Our findings demonstrate the importance of investigating sex differences, which may lead to a better understanding of disease mechanisms with a potential relevance to treatment options.
Théry, Clotilde ; Witwer, Kenneth W. ; Aikawa, Elena ; Alcaraz, Maria Jose ; Anderson, Johnathon D. ; Andriantsitohaina, Ramaroson ; Antoniou, Anna ; Arab, Tanina ; Archer, Fabienne ; Atkin-Smith, Georgia K. ; Ayre, D. Craig ; Bach, Jean-Marie ; Bachurski, Daniel ; Baharvand, Hossein ; Balaj, Leonora ; Baldacchino, Shawn ; Bauer, Natalie N. ; Baxter, Amy A. ; Bebawy, Mary ; Beckham, Carla ; Zavec, Apolonija Bedina ; Benmoussa, Abderrahim ; Berardi, Anna C. ; Bergese, Paolo ; Bielska, Ewa ; Blenkiron, Cherie ; Bobis-Wozowicz, Sylwia ; Boilard, Eric ; Boireau, Wilfrid ; Bongiovanni, Antonella ; Borràs, Francesc E. ; Bosch, Steffi ; Boulanger, Chantal M. ; Breakefield, Xandra ; Breglio, Andrew M. ; Brennan, Meadhbh Aín ; Brigstock, David R. ; Brisson, Alain ; Broekman, Marike L. D. ; Bromberg, Jacqueline F. ; Bryl-Gorecka, Paulina ; Buch, Shilpa ; Buck, Amy H. ; Burger, Dylan ; Busatto, Sara ; Buschmann, Dominik ; Bussolati, Benedetta ; Buzás, Edit I. ; Byrd, James Bryan ; Camussi, Giovanni ; Carter, David R. F. ; Caruso, Sarah ; Chamley, Lawrence W. ; Chang, Yu-Ting ; Chen, Chihchen ; Chen, Shuai ; Cheng, Lesley ; Chin, Andrew R. ; Clayton, Aled ; Clerici, Stefano P. ; Cocks, Alex ; Cocucci, Emanuele ; Coffey, Robert J. ; Cordeiro-da-Silva, Anabela ; Couch, Yvonne ; Coumans, Frank A. W. ; Coyle, Beth ; Crescitelli, Rossella ; Criado, Miria Ferreira ; D’Souza-Schorey, Crislyn ; Das, Saumya ; Chaudhuri, Amrita Datta ; de-Candia, Paola ; De Santana, Eliezer F. ; De Wever, Olivier ; del Portillo, Hernando A. ; Demaret, Tanguy ; Deville, Sarah ; Devitt, Andrew ; Dhondt, Bert ; Di Vizio, Dolores ; Dieterich, Lothar C. ; Dolo, Vincenza ; Dominguez Rubio, Ana Paula ; Dominici, Massimo ; Dourado, Mauricio R. ; Driedonks, Tom A. P. ; Duarte, Filipe V. ; Duncan, Heather M. ; Eichenberger, Ramon Marc ; Ekström, Karin ; El Andaloussi, Samir ; Elie-Caille, Celine ; Erdbrügger, Uta ; Falcón-Pérez, Juan M. ; Fatima, Farah ; Fish, Jason E. ; Flores-Bellver, Miguel ; Försönits, András ; Frelet-Barrand, Annie ; Fricke, Fabia ; Fuhrmann, Gregor ; Gabrielsson, Susanne ; Gámez-Valero, Ana ; Gardiner, Chris ; Gärtner, Kathrin ; Gaudin, Raphael ; Gho, Yong Song ; Giebel, Bernd ; Gilbert, Caroline ; Gimona, Mario ; Giusti, Ilaria ; Goberdhan, Deborah C. I. ; Görgens, André ; Gorski, Sharon M. ; Greening, David W. ; Groß, Julia Christina ; Gualerzi, Alice ; Gupta, Gopal N. ; Gustafson, Dakota ; Handberg, Aase ; Haraszti, Réka Ágnes ; Harrison, Paul ; Hegyesi, Hargita ; Hendrix, An ; Hill, Andrew F. ; Hochberg, Fred H. ; Hoffmann, Karl F. ; Holder, Beth ; Holthofer, Harry ; Hosseinkhani, Baharak ; Hu, Guoku ; Huang, Yiyao ; Huber, Veronica ; Hunt, Stuart ; Ibrahim, Ahmed Gamal-Eldin ; Ikezu, Tsuneya ; Inal, Jameel M. ; Isin, Mustafa ; Ivanova, Alena ; Jackson, Hannah K. ; Jacobsen, Soren ; Jay, Steven M. ; Jayachandran, Muthuvel ; Jenster, Guido ; Jiang, Lanzhou ; Johnson, Suzanne M. ; Jones, Jennifer C. ; Jong, Ambrose ; Jovanovic-Talisman, Tijana ; Jung, Stephanie ; Kalluri, Raghu ; Kano, Shin-ichi ; Kaur, Sukhbir ; Kawamura, Yumi ; Keller, Evan T. ; Khamari, Delaram ; Khomyakova, Elena ; Khvorova, Anastasia ; Kierulf, Peter ; Kim, Kwang Pyo ; Kislinger, Thomas ; Klingeborn, Mikael ; Klinke, David J. ; Kornek, Miroslaw ; Kosanović, Maja M. ; Kovács, Árpád Ferenc ; Krämer-Albers, Eva-Maria ; Krasemann, Susanne ; Krause, Mirja ; Kurochkin, Igor V. ; Kusuma, Gina D. ; Kuypers, Sören ; Laitinen, Saara ; Langevin, Scott M. ; Languino, Lucia R. ; Lannigan, Joanne ; Lässer, Cecilia ; Laurent, Louise C. ; Lavieu, Gregory ; Lázaro-Ibáñez, Elisa ; Le Lay, Soazig ; Lee, Myung-Shin ; Lee, Yi Xin Fiona ; Lemos, Debora S. ; Lenassi, Metka ; Leszczynska, Aleksandra ; Li, Isaac T. S. ; Liao, Ke ; Libregts, Sten F. ; Ligeti, Erzsebet ; Lim, Rebecca ; Lim, Sai Kiang ; Linē, Aija ; Linnemannstöns, Karen ; Llorente, Alicia ; Lombard, Catherine Ann ; Lorenowicz, Magdalena J. ; Lörincz, Ákos M. ; Lötvall, Jan ; Lovett, Jason ; Lowry, Michelle C. ; Loyer, Xavier ; Lu, Quan ; Lukomska, Barbara ; Lunavat, Taral Rameshchand ; Maas, Sybren L. N. ; Malhi, Harmeet ; Marcilla, Antonio ; Mariani, Jacopo ; Mariscal, Javier ; Martens-Uzunova, Elena S. ; Martin-Jaular, Lorena ; Martinez, M. Carmen ; Martins, Vilma Regina ; Mathieu, Mathilde ; Mathivanan, Suresh ; Maugeri, Marco ; McGinnis, Lynda K. ; McVey, Mark J. ; Meckes, David G. ; Meehan, Katie ; Mertens, Inge ; Minciacchi, Valentina R. ; Möller, Andreas ; Møller Jørgensen, Malene ; Morales-Kastresana, Aizea ; Morhayim, Jess ; Mullier, François ; Muraca, Maurizio ; Musante, Luca ; Mussack, Veronika ; Muth, Dillon C. ; Myburgh, Kathryn H. ; Najrana, Tanbir ; Nawaz, Muhammad ; Nazarenko, Irina ; Nejsum, Peter ; Neri, Christian ; Neri, Tommaso ; Nieuwland, Rienk ; Nimrichter, Leonardo ; Nolan, John P. ; Nolte-’t Hoen, Esther N. M. ; Hooten, Nicole Noren ; O’Driscoll, Lorraine ; O’Grady, Tina ; O’Loghlen, Ana ; Ochiya, Takahiro ; Olivier, Martin ; Ortiz, Alberto ; Ortiz, Luis A. ; Osteikoetxea, Xabier ; Østergaard, Ole ; Ostrowski, Matias ; Park, Jaesung ; Pegtel, Dirk Michiel ; Peinado, Hector ; Perut, Francesca ; Pfaffl, Michael ; Phinney, Donald G. ; Pieters, Bartijn C. H. ; Pink, Ryan Charles ; Pisetsky, David S. ; Pogge von Strandmann, Elke ; Polakovicova, Iva ; Poon, Ivan K. H. ; Powell, Bonita H. ; Prada, Ilaria ; Pulliam, Lynn ; Quesenberry, Peter ; Radeghieri, Annalisa ; Raffai, Robert L. ; Raimondo, Stefania ; Rak, Janusz ; Ramirez, Marcel I. ; Raposo, Graça ; Rayyan, Morsi S. ; Regev-Rudzki, Neta ; Ricklefs, Franz Lennard ; Robbins, Paul D. ; Roberts, David D. ; Rodrigues, Silvia C. ; Rohde, Eva ; Rome, Sophie ; Rouschop, Kasper M. ; Rughetti, Aurelia ; Russell, Ashley E. ; Saá, Paula ; Sahoo, Susmita ; Salas-Huenuleo, Edison ; Sánchez, Catherine ; Saugstad, Julie A. ; Saul, Meike J. ; Schiffelers, Raymond M. ; Schneider, Raphael ; Schøyen, Tine Hiorth ; Scott, Aaron ; Shahaj, Eriomina ; Sharma, Shivani ; Shatnyeva, Olga ; Shekari, Faezeh ; Shelke, Ganesh Vilas ; Shetty, Ashok K. ; Shiba, Kiyotaka ; Siljander, Pia R.-M. ; Silva, Andreia M. ; Skowronek, Agata ; Snyder, Orman L. ; Soares, Rodrigo Pedro ; Sódar, Barbara W. ; Soekmadji, Carolina ; Sotillo, Javier ; Stahl, Philip D. ; Stoorvogel, Willem ; Stott, Shannon L. ; Strasser, Erwin F. ; Swift, Simon ; Tahara, Hidetoshi ; Tewari, Muneesh ; Timms, Kate ; Tiwari, Swasti ; Tixeira, Rochelle ; Tkach, Mercedes ; Toh, Wei Seong ; Tomasini, Richard ; Torrecilhas, Ana Claudia ; Tosar, Juan Pablo ; Toxavidis, Vasilis ; Urbanelli, Lorena ; Vader, Pieter ; Balkom, Bastiaan Wilhelmus Maria van ; Grein, Susanne G. van der ; Van Deun, Jan ; Herwijnen, Martijn J. C. van ; Van Keuren-Jensen, Kendall R. ; Niel, Guillaume van ; Royen, Martin E. van ; Wijnen, Andre J. van ; Vasconcelos, M. Helena ; Vechetti, Ivan J. ; Veit, Tiago D. ; Vella, Laura J. ; Velot, Émilie ; Verweij, Frederik ; Vestad, Beate ; Viñas, Jose Luis ; Visnovitz, Tamás ; Vukman, Krisztina V. ; Wahlgren, Jessica ; Watson, Dionysios C. ; Wauben, Marca H. M. ; Weaver, Alissa ; Webber, Jason P. ; Weber, Viktoria ; Wehman, Ann M. ; Weiss, Daniel J. ; Welsh, Joshua A. ; Wendt, Sebastian ; Wheelock, Åsa M. ; Wiener, Zoltán ; Witte, Leonie ; Wolfram, Joy ; Xagorari, Angeliki ; Xander, Patricia ; Xu, Jing ; Yan, Xiaomei ; Yáñez-Mó, María ; Yin, Hang ; Yuana, Yuana ; Zappulli, Valentina ; Zarubova, Jana ; Žėkas, Vytautas ; Zhang, Jian-ye ; Zhao, Zezhou ; Zheng, Lei ; Zheutlin, Alexander R. ; Zickler, Antje Maria ; Zimmermann, Pascale ; Zivkovic, Angela M. ; Zocco, Davide ; Zuba-Surma, Ewa K.
The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
Lehtipalo, Katrianne ; Rondo, Linda ; Kontkanen, Jenni ; Schobesberger, Siegfried ; Jokinen, Tuija ; Sarnela, Nina ; Kürten, Christoph Andreas ; Ehrhart, Sebastian ; Franchin, Alessandro ; Nieminen, Tuomo ; Riccobono, Francesco ; Sipilä, Mikko ; Yli-Juuti, Taina ; Duplissy, Jonathan ; Adamov, Alexey ; Ahlm, Lars ; Almeida, Joao ; Amorim, Antonio ; Bianchi, Federico ; Breitenlechner, Martin ; Dommen, Josef ; Downard, Andrew ; Dunne, Eimear M. ; Flagan, Richard C. ; Guida, Roberto ; Hakala, Jani ; Hansel, Armin ; Jud, Werner ; Kangasluoma, Juha ; Kerminen, Veli-Matti ; Keskinen, Helmi ; Kim, Jaeseok ; Kirkby, Jasper ; Kupc, Agnieszka ; Kupiainen-Määttä, Oona ; Laaksonen, Ari ; Lawler, Michael Joseph ; Leiminger, Markus ; Mathot, Serge ; Olenius, Tinja ; Ortega, Ismael K. ; Onnela, Antti ; Petäjä, Tuukka ; Praplan, Arnaud Patrick ; Rissanen, Matti P. ; Ruuskanen, Taina ; Santos, Filipe Duarte ; Schallhart, Simon ; Schnitzhofer, Ralf ; Simon, Mario ; Smith, James N. ; Tröstl, Jasmin ; Tsagkogeorgas, Georgios ; Tomé, Antonio ; Vaattovaara, Petri ; Vehkamäki, Hanna ; Vrtala, Aron ; Wagner, Paul E. ; Williamson, Christina ; Wimmer, Daniela ; Winkler, Paul M. ; Virtanen, Annele ; Donahue, Neil McPherson ; Carslaw, Kenneth S. ; Baltensperger, Urs ; Riipinen, Ilona ; Curtius, Joachim ; Worsnop, Douglas R. ; Kulmala, Markku
The growth of freshly formed aerosol particles can be the bottleneck in their survival to cloud condensation nuclei. It is therefore crucial to understand how particles grow in the atmosphere. Insufficient experimental data has impeded a profound understanding of nano-particle growth under atmospheric conditions. Here we study nano-particle growth in the CLOUD (Cosmics Leaving OUtdoors Droplets) chamber, starting from the formation of molecular clusters. We present measured growth rates at sub-3 nm sizes with different atmospherically relevant concentrations of sulphuric acid, water, ammonia and dimethylamine. We find that atmospheric ions and small acid-base clusters, which are not generally accounted for in the measurement of sulphuric acid vapour, can participate in the growth process, leading to enhanced growth rates. The availability of compounds capable of stabilizing sulphuric acid clusters governs the magnitude of these effects and thus the exact growth mechanism. We bring these observations into a coherent framework and discuss their significance in the atmosphere.
Escott-Price, Valentina ; Bellenguez, Céline ; Wang, Li-San ; Choi, Seung-Hoan ; Harold, Denise ; Jones, Lesley ; Holmans, Peter ; Gerrish, Amy ; Vedernikov, Alexey ; Richards, Alexander ; DeStefano, Anita L. ; Lambert, Jean-Charles ; Ibrahim-Verbaas, Carla A. ; Naj, Adam C. ; Sims, Rebecca ; Jun, Gyungah ; Bis, Joshua C. ; Beecham, Gary W. ; Grenier-Boley, Benjamin ; Russo, Giancarlo ; Thornton-Wells, Tricia A. ; Denning, Nicola ; Smith, Albert V. ; Chouraki, Vincent ; Thomas, Charlene ; Ikram, M. Arfan ; Zelenika, Diana ; Vardarajan, Badri N. ; Kamatani, Yoichiro ; Lin, Chiao-Feng ; Schmidt, Helena ; Kunkle, Brian ; Dunstan, Melanie L. ; Vronskaya, Maria ; Johnson, Andrew D. ; Ruiz, Agustin ; Bihoreau, Marie-Thérèse ; Reitz, Christiane ; Pasquier, Florence ; Hollingworth, Paul ; Hanon, Olivier ; Fitzpatrick, Annette L. ; Buxbaum, Joseph D. ; Campion, Dominique ; Crane, Paul K. ; Baldwin, Clinton ; Becker, Tim ; Gudnason, Vilmundur ; Cruchaga, Carlos ; Craig, David ; Amin, Najaf ; Berr, Claudine ; Lopez, Oscar L. ; Jager, Philip L. De ; Deramecourt, Vincent ; Johnston, Janet A. ; Evans, Denis ; Lovestone, Simon ; Letenneur, Luc ; Hernández, Isabel ; Rubinsztein, David C. ; Eiriksdottir, Gudny ; Sleegers, Kristel ; Goate, Alison M. ; Fiévet, Nathalie ; Huentelman, Matthew J. ; Gill, Michael ; Brown, Kristelle ; Kamboh, M. Ilyas ; Keller, Lina ; Barberger-Gateau, Pascale ; McGuinness, Bernadette ; Larson, Eric B. ; Myers, Amanda J. ; Dufouil, Carole ; Todd, Stephen ; Wallon, David ; Love, Seth ; Rogaeva, Ekaterina ; Gallacher, John ; St George-Hyslop, Peter ; Clarimon, Jordi ; Lleo, Alberto ; Bayer, Anthony ; Tsuang, Debby W. ; Yu, Lei ; Tsolaki, Magda ; Bossù, Paola ; Spalletta, Gianfranco ; Proitsi, Petra ; Collinge, John ; Sorbi, Sandro ; Sanchez Garcia, Florentino ; Fox, Nick C. ; Hardy, John ; Deniz Naranjo, Maria Candida ; Bosco, Paolo ; Clarke, Robert ; Brayne, Carol ; Galimberti, Daniela ; Scarpini, Elio ; Bonuccelli, Ubaldo ; Mancuso, Michelangelo ; Siciliano, Gabriele ; Moebus, Susanne ; Mecocci, Patrizia ; Del Zompo, Maria ; Maier, Wolfgang ; Hampel, Harald ; Pilotto, Alberto ; Frank-García, Ana ; Panza, Francesco ; Solfrizzi, Vincenzo ; Caffarra, Paolo ; Nacmias, Benedetta ; Perry, William ; Mayhaus, Manuel ; Lannfelt, Lars ; Hakonarson, Hakon ; Pichler, Sabrina ; Carrasquillo, Minerva M. ; Ingelsson, Martin ; Beekly, Duane ; Alvarez, Victoria ; Zou, Fanggeng ; Valladares, Otto ; Younkin, Steven G. ; Coto, Eliecer ; Hamilton-Nelson, Kara L. ; Gu, Wei ; Razquin, Cristina ; Pastor, Pau ; Mateo, Ignacio ; Owen, Michael J. ; Faber, Kelley M. ; Jonsson, Palmi V. ; Combarros, Onofre ; O'Donovan, Michael C. ; Cantwell, Laura B. ; Soininen, Hilkka ; Blacker, Deborah ; Mead, Simon ; Mosley, Thomas H. ; Bennett, David A. ; Harris, Tamara B. ; Fratiglioni, Laura ; Holmes, Clive ; Bruijn, Renee F. A. G. de ; Passmore, Peter ; Montine, Thomas J. ; Bettens, Karolien ; Rotter, Jerome I. ; Brice, Alexis ; Morgan, Kevin ; Foroud, Tatiana M. ; Kukull, Walter A. ; Hannequin, Didier ; Powell, John F. ; Nalls, Michael A. ; Ritchie, Karen ; Lunetta, Kathryn L. ; Kauwe, John S. K. ; Boerwinkle, Eric ; Riemenschneider, Matthias ; Boada, Mercè ; Hiltunen, Mikko ; Martin, Eden R. ; Schmidt, Reinhold ; Rujescu, Dan ; Dartigues, Jean-François ; Mayeux, Richard ; Tzourio, Christophe ; Hofman, Albert ; Nöthen, Markus Maria ; Graff, Caroline ; Psaty, Bruce M. ; Haines, Jonathan L. ; Lathrop, Mark ; Pericak-Vance, Margaret Ann ; Launer, Lenore J. ; Broeckhoven, Christine Van ; Farrer, Lindsay A. ; Duijn, Cornelia M. van ; Ramirez, Alfredo ; Seshadri, Sudha ; Schellenberg, Gerard D. ; Amouyel, Philippe ; Williams, Julie
Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls.
Principal findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10−6) and 14 (IGHV1-67 p = 7.9×10−8) which indexed novel susceptibility loci.
Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
Smith, Benjamin ; Wårlind, David ; Arneth, Almut ; Hickler, Thomas ; Leadley, Paul W. ; Siltberg, Joe ; Zaehle, Sönke
The LPJ-GUESS dynamic vegetation model uniquely combines an individual- and patch-based representation of vegetation dynamics with ecosystem biogeochemical cycling from regional to global scales. We present an updated version that includes plant and soil N dynamics, analysing the implications of accounting for C-N interactions on predictions and performance of the model. Stand structural dynamics and allometric scaling of tree growth suggested by global databases of forest stand structure and development were well-reproduced by the model in comparison to an earlier multi-model study. Accounting for N cycle dynamics improved the goodness-of-fit for broadleaved forests. N limitation associated with low N mineralisation rates reduces productivity of cold-climate and dry-climate ecosystems relative to mesic temperate and tropical ecosystems. In a model experiment emulating free-air CO2 enrichment (FACE) treatment for forests globally, N-limitation associated with low N mineralisation rates of colder soils reduces CO2-enhancement of NPP for boreal forests, while some temperate and tropical forests exhibit increased NPP enhancement. Under a business-as-usual future climate and emissions scenario, ecosystem C storage globally was projected to increase by c. 10 %; additional N requirements to match this increasing ecosystem C were within the high N supply limit estimated on stoichiometric grounds in an earlier study. Our results highlight the importance of accounting for C-N interactions not only in studies of global terrestrial C cycling, but to understand underlying mechanisms on local scales and in different regional contexts.
Bowen, Tom ; Cicardi, Marco ; Farkas, Henriette ; Bork, Konrad ; Longhurst, Hilary ; Zuraw, Bruce ; Aygören-Pürsün, Emel ; Craig, Timothy ; Binkley, Karen ; Hebert, Jacques ; Ritchie, Bruce ; Bouillet, Laurence ; Betschel, Stephen ; Cogar, Della ; Dean, John ; Devaraj, Ramachand ; Hamed, Azza ; Kamra, Palinder ; Keith, Paul K. ; Lacuesta, Gina ; Leith, Eric ; Lyons, Harriet ; Mace, Sean ; Mako, Barbara ; Neurath, Doris ; Poon, Man-Chiu ; Rivard, Georges-Etienne ; Schellenberg, Robert ; Rowan, Dereth ; Rowe, Anne ; Stark, Donald ; Sur, Smeeksha ; Tsai, Ellie ; Warrington, Richard ; Waserman, Susan ; Ameratunga, Rohan ; Bernstein, Jonathan A. ; Björkander, Janne ; Brosz, Kristylea ; Brosz, John ; Bygum, Anette ; Caballero, Teresa ; Frank, Mike ; Fust, George ; Harmat, George ; Kanani, Amin ; Kreuz, Wolfhart ; Levi, Marcel M. ; Li, Henry ; Martinez Saguer, Inmaculada ; Moldovan, Dumitru ; Nagy, Istvan ; Nielsen, Erik W. ; Nordenfelt, Patrik ; Reshef, Avner ; Rusicke, Eva ; Smith-Foltz, Sarah ; Späth, Peter ; Varga, Lilian ; Xiang, Zhi Yu
Background We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency) and updated this as Hereditary angioedema: a current state-of-the-art review: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema. Objective To update the International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema (circa 2010). Methods The Canadian Hereditary Angioedema Network (CHAEN)/Reseau Canadien d'angioedeme hereditaire (RCAH) (www.haecanada.com) and cosponsors University of Calgary and the Canadian Society of Allergy and Clinical Immunology (with an unrestricted educational grant from CSL Behring) held our third Conference May 15th to 16th, 2010 in Toronto Canada to update our consensus approach. The Consensus document was reviewed at the meeting and then circulated for review. Results This manuscript is the 2010 International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema that resulted from that conference. Conclusions Consensus approach is only an interim guide to a complex disorder such as HAE and should be replaced as soon as possible with large phase III and IV clinical trials, meta analyses, and using data base registry validation of approaches including quality of life and cost benefit analyses, followed by large head-to-head clinical trials and then evidence-based guidelines and standards for HAE disease management.
Smith, Benjamin ; Wårlind, David ; Arneth, Almut ; Hickler, Thomas ; Leadley, Paul W. ; Siltberg, Joe ; Zaehle, Sönke
The LPJ-GUESS dynamic vegetation model uniquely combines an individual- and patch-based representation of vegetation dynamics with ecosystem biogeochemical cycling from regional to global scales. We present an updated version that includes plant and soil N dynamics, analysing the implications of accounting for C–N interactions on predictions and performance of the model. Stand structural dynamics and allometric scaling of tree growth suggested by global databases of forest stand structure and development were well reproduced by the model in comparison to an earlier multi-model study. Accounting for N cycle dynamics improved the goodness of fit for broadleaved forests. N limitation associated with low N-mineralisation rates reduces productivity of cold-climate and dry-climate ecosystems relative to mesic temperate and tropical ecosystems. In a model experiment emulating free-air CO2 enrichment (FACE) treatment for forests globally, N limitation associated with low N-mineralisation rates of colder soils reduces CO2 enhancement of net primary production (NPP) for boreal forests, while some temperate and tropical forests exhibit increased NPP enhancement. Under a business-as-usual future climate and emissions scenario, ecosystem C storage globally was projected to increase by ca. 10%; additional N requirements to match this increasing ecosystem C were within the high N supply limit estimated on stoichiometric grounds in an earlier study. Our results highlight the importance of accounting for C–N interactions in studies of global terrestrial N cycling, and as a basis for understanding mechanisms on local scales and in different regional contexts.
New records of Myrmeleontidae from Paraguay are presented: Dimares elegans (Perty, 1833), Glenurus croesus Banks, 1922, Glenurus penningtoni (Navás, 1918a) and Vella fallax (Rambur, 1842). The total number of species now recorded from the country is fourteen among 11 genera. Specimens of Dimares elegans from east (Cerrado) and west (Chaco) of the Paraguay River are phenotypically distinct; those west of the Paraguay River are assigned to the form “lepida” Navás, 1912. More research is required to understand the taxonomic limits in this genus.
Amaducci, Simone ; Colonna, Nicola ; Cosentino, Luigi ; Cristallo, Sergio ; Finocchiaro, Paolo ; Krtička, Milan ; Massimi, Cristian ; Mastromarco, Mario ; Mazzone, Annamaria ; Mengoni, Alberto ; Valenta, Stanislav ; Aberle, Oliver ; Alcayne, Victor ; Andrzejewski, Józef ; Audouin, Laurent ; Babiano Suarez, Victor ; Bacak, Michael ; Barbagallo, Massimo ; Bennett, Samuel ; Berthoumieux, Eric ; Billowes, Jonathan ; Bosnar, Damir ; Brown, Adam ; Busso, Maurizio ; Caamaño, Manuel ; Caballero Ontanaya, Luis ; Calviño Tavares, Francisco ; Calviani, Marco ; Cano-Ott, Daniel ; Casanovas Hoste, Adrià ; Cerutti, Francesco ; Chiaveri, Enrico ; Cortés Rossell, Guillem Pere ; Cortés-Giraldo, Miguel Antonio ; Damone, Lucia-Anna ; Davies, Paul-John ; Diakaki, Maria ; Dietz, Mirco ; Domingo-Pardo, César ; Dressler, Rugard ; Ducasse, Quentin ; Dupont, Emmeric ; Durán, Ignacio ; Eleme, Zinovia ; Fernández Domínguez, Beatriz ; Ferrari, Alfredo ; Furman, Valter ; Göbel, Kathrin ; Garg, Ruchi ; Gawlik, Aleksandra ; Gilardoni, Simone ; Gonçalves, Isabel Maria Ferro ; González Romero, Enrique Miguel ; Guerrero Sánchez, Carlos ; Gunsing, Frank ; Harada, Hideo ; Heinitz, Stephan ; Heyse, Jan ; Jenkins, David ; Junghans, Arnd Rudolf ; Käppeler, Franz ; Kadi, Yacine ; Kimura, Atsushi ; Knapová, Ingrid ; Kokkoris, Michael ; Kopatch, Yuri N. ; Kurtulgil, Cem Deniz ; Ladarescu, Ion ; Lederer-Woods, Claudia ; Leeb, Helmut ; Lerendegui-Marco, Jorge ; Lonsdale, Sarah-Jane ; Macina, Daniela ; Manna, Alice ; Martínez, Trinitario ; Masi, Alessandro ; Mastinu, Pierfrancesco ; Maugeri, Emilio Andrea ; Mendoza Cembranos, Emilio ; Michalopoulou, Veatriki ; Milazzo, Paolo Maria ; Mingrone, Federica ; Moreno-Soto, Javier ; Musumarra, Agatino ; Negret, Alexandru ; Ogállar Ruiz, Francisco ; Oprea, Andreea ; Patronis, Nikolas ; Pavlik, Andreas ; Perkowski, Jarosław ; Piersanti, Luciano ; Petrone, Cristina ; Pirovano, Elisa ; Porras Sánchez, José Ignacio ; Praena, Javier ; Quesada Molina, José Manuel ; Ramos Doval, Diego ; Rauscher, Thomas ; Reifarth, René ; Rochman, Dimitri ; Rubbia, Carlo ; Sabaté-Gilarte, Marta ; Saxena, Alok ; Schillebeeckx, Peter ; Schumann, Dorothea ; Sekhar, Adhitya ; Smith, Alastair Gavin ; Sosnin, Nikolay V. ; Sprung, Peter ; Stamatopoulos, Athanasios ; Tagliente, Giuseppe ; Taı́n Enríquez, José Luis ; Tarifeño-Saldivia, Ariel ; Tassan-Got, Laurent ; Thomas, Benedikt ; Torres-Sánchez, Pablo ; Tsinganis, Andrea ; Ulrich, Jiri ; Urlaß, Sebastian ; Vannini, Gianni ; Variale, Vincenzo ; Vaz, Pedro ; Ventura, Alberto ; Vescovi, Diego ; Vlachoudis, Vasilis ; Vlastou, Rosa ; Wallner, Anton ; Woods, Philip John ; Wright, Tobias ; Žugec, Petar
An accurate measurement of the 140Ce(n,γ) energy-dependent cross-section was performed at the n_TOF facility at CERN. This cross-section is of great importance because it represents a bottleneck for the s-process nucleosynthesis and determines to a large extent the cerium abundance in stars. The measurement was motivated by the significant difference between the cerium abundance measured in globular clusters and the value predicted by theoretical stellar models. This discrepancy can be ascribed to an overestimation of the 140Ce capture cross-section due to a lack of accurate nuclear data. For this measurement, we used a sample of cerium oxide enriched in 140Ce to 99.4%. The experimental apparatus consisted of four deuterated benzene liquid scintillator detectors, which allowed us to overcome the difficulties present in the previous measurements, thanks to their very low neutron sensitivity. The accurate analysis of the p-wave resonances and the calculation of their average parameters are fundamental to improve the evaluation of the 140Ce Maxwellian-averaged cross-section.