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  • 1. Alex, Amal
    et al.
    Piano, Valentina
    Polley, Soumitra
    Stuiver, Marchel
    Voss, Stephanie
    Ciossani, Giuseppe
    Overlack, Katharina
    Voss, Beate
    Wohlgemuth, Sabine
    Petrovic, Arsen
    Wu, Yao-Wen
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Selenko, Philipp
    Musacchio, Andrea
    Maffini, Stefano
    Electroporated recombinant proteins as tools for in vivo functional complementation, imaging and chemical biology2019In: eLIFE, E-ISSN 2050-084X, Vol. 8, article id e48287Article in journal (Refereed)
    Abstract [en]

    Delivery of native or chemically modified recombinant proteins into mammalian cells shows promise for functional investigations and various technological applications, but concerns that sub-cellular localization and functional integrity of delivered proteins may be affected remain high. Here, we surveyed batch electroporation as a delivery tool for single polypeptides and multi-subunit protein assemblies of the kinetochore, a spatially confined and well-studied subcellular structure. After electroporation into human cells, recombinant fluorescent Ndc80 and Mis12 multi-subunit complexes exhibited native localization, physically interacted with endogenous binding partners, and functionally complemented depleted endogenous counterparts to promote mitotic checkpoint signaling and chromosome segregation. Farnesylation is required for kinetochore localization of the Dynein adaptor Spindly. In cells with chronically inhibited farnesyl transferase activity, in vitro farnesylation and electroporation of recombinant Spindly faithfully resulted in robust kinetochore localization. Our data show that electroporation is well-suited to deliver synthetic and chemically modified versions of functional proteins, and, therefore, constitutes a promising tool for applications in chemical and synthetic biology.

  • 2.
    Anderl, Ines
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Laboratory of Genetic Immunology, BioMediTech, University of Tampere, Tampere, Finland.
    Hultmark, Dan
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Laboratory of Genetic Immunology, BioMediTech, University of Tampere, Tampere, Finland.
    New ways to make a blood cell2015In: eLIFE, E-ISSN 2050-084X, Vol. 4, article id e06877Article in journal (Other academic)
  • 3. Bentham, James
    et al.
    Di Cesare, Mariachiara
    Stevens, Gretchen A.
    Zhou, Bin
    Bixby, Honor
    Cowan, Melanie
    Fortunato, Lea
    Bennett, James E.
    Danaei, Goodarz
    Hajifathalian, Kaveh
    Lu, Yuan
    Riley, Leanne M.
    Laxmaiah, Avula
    Kontis, Vasilis
    Paciorek, Christopher J.
    Riboli, Elio
    Ezzati, Majid
    Abdeen, Ziad A.
    Hamid, Zargar Abdul
    Abu-Rmeileh, Niveen M.
    Acosta-Cazares, Benjamin
    Adams, Robert
    Aekplakorn, Wichai
    Aguilar-Salinas, Carlos A.
    Agyemang, Charles
    Ahmadvand, Alireza
    Ahrens, Wolfgang
    Al-Hazzaa, Hazzaa M.
    Al-Othman, Amani Rashed
    Al Raddadi, Rajaa
    Ali, Mohamed M.
    Alkerwi, Ala'a
    Alvarez-Pedrerol, Mar
    Aly, Eman
    Amouyel, Philippe
    Amuzu, Antoinette
    Andersen, Lars Bo
    Anderssen, Sigmund A.
    Anjana, Ranjit Mohan
    Aounallah-Skhiri, Hajer
    Ariansen, Inger
    Aris, Tahir
    Arlappa, Nimmathota
    Arveiler, Dominique
    Assah, Felix K.
    Avdicova, Maria
    Azizi, Fereidoun
    Babu, Bontha V.
    Bahijri, Suhad
    Balakrishna, Nagalla
    Bandosz, Piotr
    Banegas, Jose R.
    Barbagallo, Carlo M.
    Barcelo, Alberto
    Barkat, Amina
    Barros, Mauro V.
    Bata, Iqbal
    Batieha, Anwar M.
    Batista, Rosangela L.
    Baur, Louise A.
    Beaglehole, Robert
    Ben Romdhane, Habiba
    Benet, Mikhail
    Bernabe-Ortiz, Antonio
    Bernotine, Gailute
    Bettiol, Heloisa
    Bhagyalaxmi, Aroor
    Bharadwaj, Sumit
    Bhargava, Santosh K.
    Bhatti, Zaid
    Bhutta, Zulfiqar A.
    Bi, Hongsheng
    Bi, Yufang
    Bjerregaard, Peter
    Bjertness, Espen
    Bjertness, Marius B.
    Bjorkelund, Cecilia
    Blokstra, Anneke
    Bo, Simona
    Bobak, Martin
    Boddy, Lynne M.
    Boehm, Bernhard O.
    Boeing, Heiner
    Boissonnet, Carlos P.
    Bongard, Vanina
    Bovet, Pascal
    Braeckman, Lutgart
    Bragt, Marjolijn C. E.
    Brajkovich, Imperia
    Branca, Francesco
    Breckenkamp, Juergen
    Brenner, Hermann
    Brewster, Lizzy M.
    Brian, Garry R.
    Bruno, Graziella
    Bueno-de-Mesquita, H. B(as)
    Bugge, Anna
    Burns, Con
    Cabrera de Leon, Antonio
    Cacciottolo, Joseph
    Cama, Tilema
    Cameron, Christine
    Camolas, Jose
    Can, Gunay
    Candido, Ana Paula C.
    Capuano, Vincenzo
    Cardoso, Viviane C.
    Carlsson, Axel C.
    Carvalho, Maria J.
    Casanueva, Felipe F.
    Casas, Juan-Pablo
    Caserta, Carmelo A.
    Chamukuttan, Snehalatha
    Chan, Angelique W.
    Chan, Queenie
    Chaturvedi, Himanshu K.
    Chaturvedi, Nishi
    Chen, Chien-Jen
    Chen, Fangfang
    Chen, Huashuai
    Chen, Shuohua
    Chen, Zhengming
    Cheng, Ching-Yu
    Chetrit, Angela
    Chiolero, Arnaud
    Chiou, Shu-Ti
    Chirita-Emandi, Adela
    Cho, Belong
    Cho, Yumi
    Christensen, Kaare
    Chudek, Jerzy
    Cifkova, Renata
    Claessens, Frank
    Clays, Els
    Concin, Hans
    Cooper, Cyrus
    Cooper, Rachel
    Coppinger, Tara C.
    Costanzo, Simona
    Cottel, Dominique
    Cowell, Chris
    Craig, Cora L.
    Crujeiras, Ana B.
    D'Arrigo, Graziella
    d'Orsi, Eleonora
    Dallongeville, Jean
    Damasceno, Albertino
    Damsgaard, Camilla T.
    Dankner, Rachel
    Dauchet, Luc
    De Backer, Guy
    De Bacque, Dirk
    de Gaetano, Giovanni
    De Hanauw, Stefaan
    De Smedt, Delphine
    Deepa, Mohan
    Deev, Alexander D.
    Dehghan, Abbas
    Delisle, Helene
    Delpeuch, Francis
    Deschamps, Valerie
    Dhana, Klodian
    Di Castelnuovo, Augusto F.
    Dias-da-Costa, Juvenal Soares
    Diaz, Alejandro
    Djalalinia, Shirin
    Do, Ha T. P.
    Dobson, Annette J.
    Donfrancesco, Chiara
    Donoso, Silvana P.
    Doering, Angela
    Doua, Kouamelan
    Drygas, Wojciech
    Dzerve, Vilnis
    Egbagbe, Eruke E.
    Eggertsen, Robert
    Ekelund, Ulf
    El Ati, Jalila
    Elliott, Paul
    Engle-Stone, Reina
    Erasmus, Rajiv T.
    Erem, Cihangir
    Eriksen, Loise
    Escobedo-de la Pena, Jorge
    Evans, Alun
    Faeh, David
    Fall, Caroline H.
    Farzadfar, Farshad
    Felix-Redondo, Francisco J.
    Ferguson, Trevor S.
    Fernandez-Berges, Daniel
    Ferrante, Daniel
    Ferrari, Marika
    Ferreccio, Catterina
    Ferrieres, Jean
    Finn, Joseph D.
    Fischer, Krista
    Monterubio Flores, Eric
    Foeger, Bernhard
    Foo, Leng Huat
    Forslund, Ann-Sofie
    Forsner, Maria
    Umeå University, Faculty of Medicine, Department of Nursing. Högskolan Dalarna.
    Fortmann, Stephen P.
    Francis, Heba M.
    Francis, Damian K.
    do Carmo Franco, Maria
    Franco, Oscar H.
    Frontera, Guillermo
    Fuchs, Flavio D.
    Fuchs, Sandra C.
    Fujita, Yuki
    Furusawa, Takuro
    Gaciong, Zbigniew
    Gafencu, Mihai
    Gareta, Dickman
    Garnett, Sarah P.
    Gaspoz, Jean-Michel
    Gasull, Magda
    Gates, Louise
    Geleijnse, Johanna M.
    Ghasemian, Anoosheh
    Giampaoli, Simona
    Gianfagna, Francesco
    Giovannelli, Jonathan
    Giwercman, Aleksander
    Goldsmith, Rebecca A.
    Goncalves, Helen
    Gonzalez Gross, Marcela
    Gonzalez Rivas, Juan P.
    Bonet Gorbea, Mariano
    Gottrand, Frederic
    Graff-Iversen, Sidsel
    Grafnetter, Dusan
    Grajda, Aneta
    Grammatikopoulou, Maria G.
    Gregor, Ronald D.
    Grodzicki, Tomasz
    Grontved, Anders
    Gruden, Grabriella
    Grujic, Vera
    Gu, Dongfeng
    Gualdi-Russo, Emanuela
    Guan, Ong Peng
    Gudnason, Vilmundur
    Guerrero, Ramiro
    Guessous, Idris
    Guimaraes, Andre L.
    Gulliford, Martin C.
    Gunnlaugsdottir, Johanna
    Gunter, Marc
    Guo, Xiuhua
    Guo, Yin
    Gupta, Prakash C.
    Gureje, Oye
    Gurzkowska, Beata
    Gutierrez, Laura
    Gutzwiller, Felix
    Halkjaer, Jytte
    Hambleton, Ian R.
    Hardy, Rebecca
    Kumar, Rachakulla Hari
    Hata, Jun
    Hayes, Alison J.
    He, Jiang
    Hendriks, Marleen Ekisabeth
    Hernandez Cadena, Leticia
    Herrala, Sauli
    Heshmat, Ramin
    Hihtaniemi, Ilpo Tapani
    Ho, Sai Yin
    Ho, Suzanne C.
    Hobbs, Michael
    Hofman, Albert
    Hormiga, Claudi M.
    Horta, Bernardo L.
    Houti, Leila
    Howitt, Christina
    Htay, Thein Thein
    Htet, Aung Soe
    Htike, Maung Maung Than
    Hu, Yonghua
    Husseini, Abdullatif
    Huu, Chinh Nguyen
    Huybrechts, Inge
    Hwalla, Nahla
    Iacoviello, Licia
    Iannone, Anna G.
    Ibrahim, Mohsen M.
    Ikeda, Nayu
    Ikram, M. Arfan
    Irazola, Vilma E.
    Islam, Muhammad
    Ivkovic, Vanja
    Iwasaki, Masanori
    Jackson, Rod T.
    Jacobs, Jeremy M.
    Jafar, Tazeen
    Jamil, Kazi M.
    Jamrozik, Konrad
    Janszky, Imre
    Jasienska, Grazyna
    Jelakovic, Bojan
    Jiang, Chao Qiang
    Joffres, Michel
    Johansson, Mattias
    Jonas, Jost B.
    Jorgensen, Torben
    Joshi, Pradeep
    Juolevi, Anne
    Jurak, Gregor
    Juresa, Vesno
    Kaaks, Rudolf
    Kafatos, Anthony
    Kalter-Leibovici, Ofra
    Kapantais, Efthymios
    Kasaeian, Amir
    Katz, Joanne
    Kaur, Prabhdeep
    Kavousi, Maryam
    Keil, Ulrich
    Boker, Lital Keinan
    Keinanen-Kiukaanniemi, Sirkka
    Kelishadi, Roya
    Kemper, Han C. G.
    Kengne, Andre P.
    Kersting, Mathilde
    Key, Timothy
    Khader, Yousef Saleh
    Khalili, Davood
    Khang, Young-Ho
    Khaw, Kay-Tee H.
    Khouw, Ilse M. S. L.
    Kiechl, Stefan
    Killewo, Japhet
    Kim, Jeongseon
    Klimont, Jeannette
    Klumbiene, Jurate
    Koirala, Bhawesh
    Kolle, Elin
    Kolsteren, Patrick
    Korrovits, Paul
    Koskinen, Seppo
    Kouda, Katsuyasu
    Koziel, Slawomir
    Kratzer, Wolfgang
    Krokstad, Steinar
    Kromhout, Daan
    Kruger, Herculina S.
    Kubinova, Ruzena
    Kujala, Urho M.
    Kula, Krzysztof
    Kulaga, Zbigniew
    Kumar, R. Krishna
    Kurjata, Pawel
    Kusuma, Yadlapalli S.
    Kuulasmaa, Kari
    Kyobutungi, Catherine
    Laamiri, Fatima Zahra
    Laatikainen, Tiina
    Lachat, Carl
    Laid, Youcef
    Lam, Tai Hing
    Landrove, Orlando
    Lanska, Vera
    Lappas, Georg
    Larijani, Bagher
    Laugsand, Lars E.
    Bao, Khanh Le Nguyen
    Le, Tuyen D
    Leclercq, Catherine
    Lee, Jeannette
    Lee, Jeonghee
    Lehtimaki, Terho
    Lekhraj, Rampal
    Leon-Munoz, Luz M.
    Li, Yanping
    Lilly, Christa L.
    Lim, Wei-Yen
    Fernanda Lima-Costa, M.
    Lin, Hsien-Ho
    Lin, Xu
    Linneberg, Allan
    Lissner, Lauren
    Litwin, Mieczyslaw
    Liu, Jing
    Lorbeer, Roberto
    Lotufo, Paulo A.
    Eugenio Lozano, Jose
    Luksiene, Dalia
    Lundqvist, Annamari
    Lunet, Nuno
    Ma, Guansheng
    Ma, Jun
    Machado-Coelho, George L. L.
    Machi, Suka
    Maggi, Stefania
    Magliano, Dianna J.
    Maire, Bernard
    Makdisse, Marcia
    Malekzadeh, Reza
    Malhotra, Rahul
    Rao, Kodavanti Mallikharjuna
    Malyutina, Sofia
    Manios, Yannis
    Mann, Jim I.
    Manzato, Enzo
    Margozzini, Paula
    Markey, Oonagh
    Marques-Vidal, Pedro
    Marrugat, Jaume
    Martin-Prevel, Yves
    Martorell, Reynaldo
    Masoodi, Shariq R.
    Mathiesen, Ellisiv B.
    Matsha, Tandi E.
    Mazur, Artur
    Mbanya, Jean Claude N.
    McFarlane, Shelly R.
    McGarvey, Stephen T.
    McKee, Martin
    McLachlan, Stela
    McLean, Rachael M.
    McNulty, Breige A.
    Yusof, Safiah Md
    Mediene-Benchekor, Sounnia
    Meirhaeghe, Aline
    Meisinger, Christa
    Menezes, Ana Maria B.
    Mensink, Gert B. M.
    Meshram, Indrapal I.
    Metspalu, Andres
    Mi, Jie
    Michaelsen, Kim F.
    Mikkel, Kairit
    Miller, Jody C.
    Francisco Miquel, Juan
    Jaime Miranda, J.
    Misigoj-Durakovic, Marjeta
    Mohamed, Mostafa K.
    Mohammad, Kazem
    Mohammadifard, Noushin
    Mohan, Viswanathan
    Yusoff, Muhammad Fadhli Mohd
    Molbo, Drude
    Moller, Niels C.
    Molnar, Denes
    Mondo, Charles K.
    Monterrubio, Eric A.
    Monyeki, Kotsedi Daniel K.
    Moreira, Leila B.
    Morejon, Alain
    Moreno, Luis A.
    Morgan, Karen
    Mortensen, Erik Lykke
    Moschonis, George
    Mossakowska, Malgorzata
    Mostafa, Aya
    Mota, Jorge
    Motlagh, Mohammad Esmaeel
    Motta, Jorge
    Mu, Thet Thet
    Muiesan, Maria Lorenza
    Mueller-Nurasyid, Martina
    Murphy, Neil
    Mursu, Jaakko
    Murtagh, Elaine M.
    Musa, Kamarul Imran
    Musil, Vera
    Nagel, Gabriele
    Nakamura, Harunobu
    Namesna, Jana
    Nang, Ei Ei K.
    Nangia, Vinay B.
    Nankap, Martin
    Narake, Sameer
    Maria Navarrete-Munoz, Eva
    Neal, William A.
    Nenko, Ilona
    Neovius, Martin
    Nervi, Flavio
    Neuhauser, Hannelore K.
    Nguyen, Nguyen D.
    Nguyen, Quang Ngoc
    Nieto-Martinez, Ramfis E.
    Ning, Guang
    Ninomiya, Toshiharu
    Nishtar, Sania
    Noale, Marianna
    Norat, Teresa
    Noto, Davide
    Al Nsour, Mohannad
    O'Reilly, Dermot
    Oh, Kyungwon
    Olayan, Iman H.
    Anselmo Olinto, Maria Teresa
    Oltarzewski, Maciej
    Omar, Mohd A.
    Onat, Altan
    Ordunez, Pedro
    Ortiz, Ana P.
    Osler, Merete
    Osmond, Clive
    Ostojic, Sergej M.
    Otero, Johanna A.
    Overvad, Kim
    Owusu-Dabo, Ellis
    Paccaud, Fred Michel
    Padez, Cristina
    Pahomova, Elena
    Pajak, Andrzej
    Palli, Domenico
    Palloni, Alberto
    Palmieri, Luigi
    Panda-Jonas, Songhomitra
    Panza, Francesco
    Parnell, Winsome R.
    Parsaeian, Mahboubeh
    Pecin, Ivan
    Pednekar, Mangesh S.
    Peeters, Petra H.
    Peixoto, Sergio Viana
    Peltonen, Markku
    Pereira, Alexandre C.
    Perez, Cynthia M.
    Peters, Annette
    Petkeviciene, Janina
    Peykari, Niloofar
    Pham, Son Thai
    Pigeot, Iris
    Pikhart, Hynek
    Pilav, Aida
    Pilotto, Lorenza
    Pistelli, Francesco
    Pitakaka, Freda
    Piwonska, Aleksandra
    Plans-Rubio, Pedro
    Poh, Bee Koon
    Porta, Miquel
    Portegies, Marileen L. P.
    Poulimeneas, Dimitrios
    Pradeepa, Rajendra
    Prashant, Mathur
    Price, Jacqueline F.
    Puiu, Maria
    Punab, Margus
    Qasrawi, Radwan F.
    Qorbani, Mostafa
    Bao, Tran Quoc
    Radic, Ivana
    Radisauskas, Ricardas
    Rahman, Mahmudur
    Raitakari, Olli
    Raj, Manu
    Rao, Sudha Ramachandra
    Ramachandran, Ambady
    Ramke, Jacqueline
    Ramos, Rafel
    Rampal, Sanjay
    Rasmussen, Finn
    Redon, Josep
    Reganit, Paul Ferdinand M.
    Ribeiro, Robespierre
    Rigo, Fernando
    de Wit, Tobias F. Rinke
    Ritti-Dias, Raphael M.
    Rivera, Juan A.
    Robinson, Sian M.
    Robitaille, Cynthia
    Rodri-guez-Artalejo, Fernando
    del Cristo Rodriguez-Perez, Maria
    Rodriguez-Villamizar, Laura A.
    Rojas-Martinez, Rosalba
    Rojroongwasinkul, Nipa
    Romaguera, Dora
    Ronkainen, Kimmo
    Rosengren, Annika
    Rouse, Ian
    Rubinstein, Adolfo
    Ruhli, Frank J.
    Rui, Ornelas
    Sandra Ruiz-Betancourt, Blanca
    Horimoto, Andrea R. V. Russo
    Rutkowski, Marcin
    Sabanayagam, Charumathi
    Sachdev, Harshpal S.
    Saidi, Olfa
    Salanave, Benoit
    Salazar Martinez, Eduardo
    Salomaa, Veikko
    Salonen, Jukka T.
    Salvetti, Massimo
    Sanchez-Abanto, Jose
    Sandjaja,
    Sans, Susana
    Santos, Diana A.
    Santos, Osvaldo
    dos Santos, Renata Nunes
    Santos, Rute
    Saramies, Jouko L.
    Sardinha, Luis B.
    Sarrafzadegan, Nizal
    Saum, Kai-Uwe
    Savva, Savvas C.
    Scazufca, Marcia
    Rosario, Angelika Schaffrath
    Schargrodsky, Herman
    Schienkiewitz, Anja
    Schmidt, Ida Maria
    Schneider, Ione J.
    Schultsz, Constance
    Schutte, Aletta E.
    Sein, Aye Aye
    Sen, Abhijit
    Senbanjo, Idowu O.
    Sepanlou, Sadaf G.
    Shalnova, Svetlana A.
    Sharma, Sanjib K.
    Shaw, Jonathan E.
    Shibuya, Kenji
    Shin, Dong Wook
    Shin, Youchan
    Shiri, Rahman
    Siantar, Rosalynn
    Sibai, Abla M.
    Silva, Antonio M.
    Santos Silva, Diego Augusto
    Simon, Mary
    Simons, Judith
    Simons, Leon A.
    Sjostrom, Michael
    Slowikowska-Hilczer, Jolanta
    Slusarczyk, Przemyslaw
    Smeeth, Liam
    Smith, Margaret C.
    Snijder, Marieke B.
    So, Hung-Kwan
    Sobngwi, Eugene
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Soekatri, Moesijanti Y. E.
    Solfrizzi, Vincenzo
    Sonestedt, Emily
    Song, Yi
    Sorensen, Thorkild I. A.
    Soric, Maroje
    Jerome, Charles Sossa
    Soumare, Aicha
    Staessen, Jan A.
    Starc, Gregor
    Stathopoulou, Maria G.
    Staub, Kaspar
    Stavreski, Bill
    Steene-Johannessen, Jostein
    Stehle, Peter
    Stein, Aryeh D.
    Stergiou, George S.
    Stessman, Jochanan
    Stieber, Jutta
    Stoeckl, Doris
    Stocks, Tanja
    Stokwiszewski, Jakub
    Stratton, Gareth
    Stronks, Karien
    Strufaldi, Maria Wany
    Sun, Chien-An
    Sundstroem, Johan
    Sung, Yn-Tz
    Sunyer, Jordi
    Suriyawongpaisal, Paibul
    Swinburn, Boyd A.
    Sy, Rody G.
    Szponar, Lucjan
    Tai, E. Shyong
    Tammesoo, Mari-Liis
    Tamosiunas, Abdonas
    Tang, Line
    Tang, Xun
    Tanser, Frank
    Tao, Yong
    Tarawneh, Mohammed Rasoul
    Tarp, Jakob
    Tarqui-Mamani, Carolina B.
    Taylor, Anne
    Tchibindat, Felicite
    Theobald, Holger
    Thijs, Lutgarde
    Thuesen, Betina H.
    Tjonneland, Anne
    Tolonen, Hanna K.
    Tolstrup, Janne S.
    Topbas, Murat
    Topor-Madry, Roman
    Torrent, Maties
    Toselli, Stefania
    Traissac, Pierre
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Trinh, Oanh T. H.
    Trivedi, Atul
    Tshepo, Lechaba
    Tulloch-Reid, Marshall K.
    Tuomainen, Tomi-Pekka
    Tuomilehto, Jaakko
    Turley, Maria L.
    Tynelius, Per
    Tzotzas, Themistoklis
    Tzourio, Christophe
    Ueda, Peter
    Ukoli, Flora A. M.
    Ulmer, Hanno
    Unal, Belgin
    Uusitalo, Hannu M. T.
    Valdivia, Gonzalo
    Vale, Susana
    Valvi, Damaskini
    van der Schouw, Yvonne T.
    Van Herck, Koen
    Minh, Hoang Van
    van Rossem, Lenie
    van Valkengoed, Irene G. M.
    Vanderschueren, Dirk
    Vanuzzo, Diego
    Vatten, Lars
    Vega, Tomas
    Velasquez-Melendez, Gustavo
    Veronesi, Giovanni
    Verschuren, W. M. Monique
    Verstraeten, Roosmarijn
    Victora, Cesar G.
    Viegi, Giovanni
    Viet, Lucie
    Viikari-Juntura, Eira
    Vineis, Paolo
    Vioque, Jesus
    Virtanen, Jyrki K.
    Visvikis-Siest, Sophie
    Viswanathan, Bharathi
    Vollenweider, Peter
    Voutilainen, Sari
    Vrdoljak, Ana
    Vrijheid, Martine
    Wade, Alisha N.
    Wagner, Aline
    Walton, Janette
    Mohamud, Wan Nazaimoon Wan
    Wang, Ming-Dong
    Wang, Qian
    Wang, Ya Xing
    Wannamethee, S. Goya
    Wareham, Nicholas
    Weerasekera, Deepa
    Whincup, Peter H.
    Widhalm, Kurt
    Widyahening, Indah S.
    Wiecek, Andrzej
    Wijga, Alet H.
    Wilks, Rainford J.
    Willeit, Johann
    Wilsgaard, Tom
    Wojtyniak, Bogdan
    Wong, Jyh Eiin
    Wong, Tien Yin
    Woo, Jean
    Woodward, Mark
    Wu, Frederick C.
    Wu, Jianfeng
    Wu, Shou Ling
    Xu, Haiquan
    Xu, Liang
    Yamborisut, Uruwan
    Yan, Weili
    Yang, Xiaoguang
    Yardim, Nazan
    Ye, Xingwang
    Yiallouros, Panayiotis K.
    Yoshihara, Akihiro
    You, Qi Sheng
    Younger-Coleman, Novie O.
    Yusoff, Ahmad F.
    Zainuddin, Ahmad A.
    Zambon, Sabina
    Zdrojewski, Tomasz
    Zeng, Yi
    Zhao, Dong
    Zhao, Wenhua
    Zheng, Yingfeng
    Zhou, Maigeng
    Zhu, Dan
    Zimmermann, Esther
    Cisneros, Julio Zuniga
    A century of trends in adult human height2016In: eLIFE, E-ISSN 2050-084X, Vol. 5, article id e13410Article in journal (Refereed)
    Abstract [en]

    Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.

  • 4.
    Billker, Oliver
    Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
    Cracking Ali Baba's code2017In: eLIFE, E-ISSN 2050-084X, Vol. 6Article in journal (Refereed)
    Abstract [en]

    A protein called P36 holds the key to how different species of malaria parasite invade liver cells.

  • 5. de Boer, Lieke
    et al.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Dayan, Peter
    Backman, Lars
    Guitart-Masip, Marc
    Attenuation of dopamine-modulated prefrontal value signals underlies probabilistic reward learning deficits in old age2017In: eLIFE, E-ISSN 2050-084X, Vol. 6, article id e2642Article in journal (Refereed)
    Abstract [en]

    Probabilistic reward learning is characterised by individual differences that become acute in aging. This may be due to age-related dopamine (DA) decline affecting neural processing in striatum, prefrontal cortex, or both. We examined this by administering a probabilistic reward learning task to younger and older adults, and combining computational modelling of behaviour, fMRI and PET measurements of DA D1 availability. We found that anticipatory value signals in ventromedial prefrontal cortex (vmPFC) were attenuated in older adults. The strength of this signal predicted performance beyond age and was modulated by D1 availability in nucleus accumbens. These results uncover that a value-anticipation mechanism in vmPFC declines in aging, and that this mechanism is associated with DA D1 receptor availability.

  • 6. Dijk, Wieneke
    et al.
    Heine, Markus
    Vergnes, Laurent
    Boon, Mariëtte R.
    Schaart, Gert
    Hesselink, Matthijs K. C.
    Reue, Karen
    Lichtenbelt, Wouter D. van Marken
    Olivecrona, Gunilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Rensen, Patrick C. N.
    Heeren, Joerg
    Kersten, Sander
    ANGPTL4 mediates shuttling of lipid fuel to brown adipose tissue during sustained cold exposure2015In: eLIFE, E-ISSN 2050-084X, Vol. 4, article id e08428Article in journal (Refereed)
    Abstract [en]

    Brown adipose tissue (BAT) activation via cold exposure is increasingly scrutinized as a potential approach to ameliorate cardio-metabolic risk. Transition to cold temperatures requires changes in the partitioning of energy substrates, re-routing fatty acids to BAT to fuel non-shivering thermogenesis. However, the mechanisms behind the redistribution of energy substrates to BAT remain largely unknown. Angiopoietin-like 4 (ANGPTL4), a protein that inhibits lipoprotein lipase (LPL) activity, is highly expressed in BAT. Here, we demonstrate that ANGPTL4 is part of a shuttling mechanism that directs fatty acids derived from circulating triglyceride-rich lipoproteins to BAT during cold. Specifically, we show that cold markedly down-regulates ANGPTL4 in BAT, likely via activation of AMPK, enhancing LPL activity and uptake of plasma triglyceride-derived fatty acids. In contrast, cold up-regulates ANGPTL4 in WAT, abolishing a cold-induced increase in LPL activity. Together, our data indicate that ANGPTL4 is an important regulator of plasma lipid partitioning during sustained cold.

  • 7. Guan, Jikui
    et al.
    Umapathy, Ganesh
    Yamazaki, Yasuo
    Wolfstetter, Georg
    Mendoza-Garcia, Patricia
    Department of Medical Biochemistry and Cell Biology, Instititute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Pfeifer, Kathrin
    Mohammed, Ateequrrahman
    Hugosson, Fredrik
    Zhang, Hongbing
    Hsu, Amy W
    Halenbeck, Robert
    Hallberg, Bengt
    Palmer, Ruth H
    FAM150A and FAM150B are activating ligands for anaplastic lymphoma kinase2015In: eLIFE, E-ISSN 2050-084X, Vol. 4, article id e09811Article in journal (Refereed)
    Abstract [en]

    Aberrant activation of anaplastic lymphoma kinase (ALK) has been described in a range of human cancers, including non-small cell lung cancer and neuroblastoma (Hallberg and Palmer, 2013). Vertebrate ALK has been considered to be an orphan receptor and the identity of the ALK ligand(s) is a critical issue. Here we show that FAM150A and FAM150B are potent ligands for human ALK that bind to the extracellular domain of ALK and in addition to activation of wild-type ALK are able to drive 'superactivation' of activated ALK mutants from neuroblastoma. In conclusion, our data show that ALK is robustly activated by the FAM150A/B ligands and provide an opportunity to develop ALK-targeted therapies in situations where ALK is overexpressed/activated or mutated in the context of the full length receptor.

  • 8.
    Lind, Peter A
    et al.
    New Zealand Institute for Advanced Study, Massey, New; Allan Wilson Centre for Molecular Ecology and Evolution, Massey University, Auckland.
    Farr, Andrew D
    Rainey, Paul B
    Experimental evolution reveals hidden diversity in evolutionary pathways2015In: eLIFE, E-ISSN 2050-084X, Vol. 4, article id e07074Article in journal (Refereed)
    Abstract [en]

    Replicate populations of natural and experimental organisms often show evidence of parallel genetic evolution, but the causes are unclear. The wrinkly spreader morph of Pseudomonas fluorescens arises repeatedly during experimental evolution. The mutational causes reside exclusively within three pathways. By eliminating these, 13 new mutational pathways were discovered with the newly arising WS types having fitnesses similar to those arising from the commonly passaged routes. Our findings show that parallel genetic evolution is strongly biased by constraints and we reveal the genetic bases. From such knowledge, and in instances where new phenotypes arise via gene activation, we suggest a set of principles: evolution proceeds firstly via pathways subject to negative regulation, then via promoter mutations and gene fusions, and finally via activation by intragenic gain-of-function mutations. These principles inform evolutionary forecasting and have relevance to interpreting the diverse array of mutations associated with clinically identical instances of disease in humans.

  • 9.
    Lind, Peter A
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). New Zealand Institute for Advanced Study, Massey University at Albany, Auckland, New Zealand.
    Libby, Eric
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics. New Zealand Institute for Advanced Study, Massey University at Albany, Auckland, New Zealand ; 3 Santa Fe Institute, New Mexico, United States.
    Herzog, Jenny
    Rainey, Paul B
    Predicting mutational routes to new adaptive phenotypes2019In: eLIFE, E-ISSN 2050-084X, Vol. 8, p. 1-31, article id e38822Article in journal (Refereed)
    Abstract [en]

    Predicting evolutionary change poses numerous challenges. Here we take advantage of the model bacterium Pseudomonas fluorescens in which the genotype-to-phenotype map determining evolution of the adaptive ‘wrinkly spreader’ (WS) type is known. We present mathematical descriptions of three necessary regulatory pathways and use these to predict both the rate at which each mutational route is used and the expected mutational targets. To test predictions, mutation rates and targets were determined for each pathway. Unanticipated mutational hotspots caused experimental observations to depart from predictions but additional data led to refined models. A mismatch was observed between the spectra of WS-causing mutations obtained with and without selection due to low fitness of previously undetected WS-causing mutations. Our findings contribute toward the development of mechanistic models for forecasting evolution, highlight current limitations, and draw attention to challenges in predicting locus-specific mutational biases and fitness effects.

  • 10. Lump, Edina
    et al.
    Castellano, Laura M
    Meier, Christoph
    Seeliger, Janine
    Erwin, Nelli
    Sperlich, Benjamin
    Stürzel, Christina M
    Usmani, Shariq
    Hammond, Rebecca M
    von Einem, Jens
    Gerold, Gisa
    Kreppel, Florian
    Bravo-Rodriguez, Kenny
    Pietschmann, Thomas
    Holmes, Veronica M
    Palesch, David
    Zirafi, Onofrio
    Weissman, Drew
    Sowislok, Andrea
    Wettig, Burkhard
    Heid, Christian
    Kirchhoff, Frank
    Weil, Tanja
    Klärner, Frank-Gerrit
    Schrader, Thomas
    Bitan, Gal
    Sanchez-Garcia, Elsa
    Winter, Roland
    Shorter, James
    Münch, Jan
    A molecular tweezer antagonizes seminal amyloids and HIV infection2015In: eLIFE, E-ISSN 2050-084X, Vol. 4, article id e05397Article in journal (Refereed)
    Abstract [en]

    Semen is the main vector for HIV transmission and contains amyloid fibrils that enhance viral infection. Available microbicides that target viral components have proven largely ineffective in preventing sexual virus transmission. In this study, we establish that CLR01, a 'molecular tweezer' specific for lysine and arginine residues, inhibits the formation of infectivity-enhancing seminal amyloids and remodels preformed fibrils. Moreover, CLR01 abrogates semen-mediated enhancement of viral infection by preventing the formation of virion-amyloid complexes and by directly disrupting the membrane integrity of HIV and other enveloped viruses. We establish that CLR01 acts by binding to the target lysine and arginine residues rather than by a non-specific, colloidal mechanism. CLR01 counteracts both host factors that may be important for HIV transmission and the pathogen itself. These combined anti-amyloid and antiviral activities make CLR01 a promising topical microbicide for blocking infection by HIV and other sexually transmitted viruses.

  • 11.
    Mair, Andrea
    et al.
    Vienna, Austria.
    Pedrotti, Lorenzo
    Würzburg, Germany.
    Wurzinger, Bernhard
    Vienna, Austria.
    Anrather, Dorothea
    Vienna, Austria.
    Simeunovic, Andrea
    Vienna, Austria.
    Weiste, Christoph
    Würzburg, Germany.
    Valerio, Concetta
    Oeiras, Portugal.
    Dietrich, Katrin
    Würzburg, Germany.
    Kirchler, Tobias
    Tübingen, Germany.
    Nägele, Thomas
    Vienna, Austria.
    Vicente Carbajosa, Jesús
    Madrid, Spain.
    Hanson, Johannes
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Molecular Plant Physiology, Utrecht University, Utrecht, The Netherlands.
    Baena-González, Elena
    Oeiras, Portugal.
    Chaban, Christina
    Tübingen, Germany.
    Weckwerth, Wolfram
    Vienna, Austria.
    Dröge-Laser, Wolfgang
    Würzburg, Germany.
    Teige, Markus
    Vienna, Austria.
    SnRK1-triggered switch of bZIP63 dimerization mediates the low-energy response in plants2015In: eLIFE, E-ISSN 2050-084X, Vol. 4, article id e05828Article in journal (Refereed)
    Abstract [en]

    Metabolic adjustment to changing environmental conditions, particularly balancing of growth and defense responses, is crucial for all organisms to survive. The evolutionary conserved AMPK/Snf1/SnRK1 kinases are well-known metabolic master regulators in the low-energy response in animals, yeast and plants. They act at two different levels: by modulating the activity of key metabolic enzymes, and by massive transcriptional reprogramming. While the first part is well established, the latter function is only partially understood in animals and not at all in plants. Here we identified the Arabidopsis transcription factor bZIP63 as key regulator of the starvation response and direct target of the SnRK1 kinase. Phosphorylation of bZIP63 by SnRK1 changed its dimerization preference, thereby affecting target gene expression and ultimately primary metabolism. A bzip63 knock-out mutant exhibited starvation-related phenotypes, which could be functionally complemented by wild type bZIP63, but not by a version harboring point mutations in the identified SnRK1 target sites.

  • 12. Mysling, Simon
    et al.
    Kolby Kristensen, Kristian
    Larsson, Mikael
    Kovrov, Oleg
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Bensadouen, André
    Jorgensen, Thomas J. D.
    Olivecrona, Gunilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Young, Stephen G.
    Ploug, Michael
    The angiopoietin-like protein ANGPTL4 catalyzes unfolding of the hydrolase domain in lipoprotein lipase and the endothelial membrane protein GPIHBP1 counteracts this unfolding2016In: eLIFE, E-ISSN 2050-084X, Vol. 5, article id e20958Article in journal (Refereed)
    Abstract [en]

    Lipoprotein lipase (LPL) undergoes spontaneous inactivation via global unfolding and this unfolding is prevented by GPIHBP1 (Mysling et al., 2016). We now show: (1) that ANGPTL4 inactivates LPL by catalyzing the unfolding of its hydrolase domain; (2) that binding to GPIHBP1 renders LPL largely refractory to this inhibition; and (3) that both the LU domain and the intrinsically disordered acidic domain of GPIHBP1 are required for this protective effect. Genetic studies have found that a common polymorphic variant in ANGPTL4 results in lower plasma triglyceride levels. We now report: (1) that this ANGPTL4 variant is less efficient in catalyzing the unfolding of LPL; and (2) that its Glu-to-Lys substitution destabilizes its N-terminal alpha-helix. Our work elucidates the molecular basis for regulation of LPL activity by ANGPTL4, highlights the physiological relevance of the inherent instability of LPL, and sheds light on the molecular defects in a clinically relevant variant of ANGPTL4.

  • 13.
    Näsström, Elin
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Parry, Christopher M.
    Thieu, Nga Tran Vu
    Maude, Rapeephan R.
    de Jong, Hanna K.
    Fukushima, Masako
    Rzhepishevska, Olena
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Marks, Florian
    Panzner, Ursula
    Im, Justin
    Jeon, Hyonjin
    Park, Seeun
    Chaudhury, Zabeen
    Ghose, Aniruddha
    Samad, Rasheda
    Van, Tan Trinh
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Dondorp, Arjen M.
    Thwaites, Guy E.
    Faiz, Abul
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Baker, Stephen
    Reproducible diagnostic metabolites in plasma from typhoid fever patients in Asia and Africa2017In: eLIFE, E-ISSN 2050-084X, Vol. 6, article id e15651Article in journal (Refereed)
    Abstract [en]

    Salmonella Typhi is the causative agent of typhoid. Typhoid is diagnosed by blood culture, a method that lacks sensitivity, portability and speed. We have previously shown that specific metabolomic profiles can be detected in the blood of typhoid patients from Nepal (Nasstrom et al., 2014). Here, we performed mass spectrometry on plasma from Bangladeshi and Senegalese patients with culture confirmed typhoid fever, clinically suspected typhoid, and other febrile diseases including malaria. After applying supervised pattern recognition modelling, we could significantly distinguish metabolite profiles in plasma from the culture confirmed typhoid patients. After comparing the direction of change and degree of multivariate significance, we identified 24 metabolites that were consistently up- or down regulated in a further Bangladeshi/Senegalese validation cohort, and the Nepali cohort from our previous work. We have identified and validated a metabolite panel that can distinguish typhoid from other febrile diseases, providing a new approach for typhoid diagnostics.

  • 14.
    Näsström, Elin
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Thieu, Nga Tran Vu
    Dongol, Sabina
    Karkey, Abhilasha
    Vinh, Phat Voong
    Thanh, Tuyen Ha
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Arjyal, Amit
    Thwaites, Guy
    Dolecek, Christiane
    Basnyat, Buddha
    Baker, Stephen
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Salmonella Typhi and Salmonella Paratyphi A elaborate distinct systemic metabolite signatures during enteric fever2014In: eLIFE, E-ISSN 2050-084X, Vol. 3, article id e03100Article in journal (Refereed)
    Abstract [en]

    The host-pathogen interactions induced by Salmonella Typhi and Salmonella Paratyphi A during enteric fever are poorly understood. This knowledge gap, and the human restricted nature of these bacteria, limit our understanding of the disease and impede the development of new diagnostic approaches. To investigate metabolite signals associated with enteric fever we performed two-dimensional gas chromatography with time-of-flight mass spectrometry (GCxGC/TOFMS) on plasma from patients with S. Typhi and S. Paratyphi A infections and asymptomatic controls, identifying 695 individual metabolite peaks. Applying supervised pattern recognition, we found highly significant and reproducible metabolite profiles separating S. Typhi cases, S. Paratyphi A cases, and controls, calculating that a combination of six metabolites could accurately define the etiological agent. For the first time we show that reproducible and serovar specific systemic biomarkers can be detected during enteric fever. Our work defines several biologically plausible metabolites that can be used to detect enteric fever, and unlocks the potential of this method in diagnosing other systemic bacterial infections.

  • 15. Pfeiffer, Anne
    et al.
    Janocha, Denis
    Dong, Yihan
    Medzihradszky, Anna
    Schöne, Stefanie
    Daum, Gabor
    Suzaki, Takuya
    Forner, Joachim
    Longenecker, Tobias
    Rempel, Eugen
    Schmid, Markus
    Department of Molecular Biology, Max Planck Institute for Developmental Biology, Tübingen, Germany.
    Wirtz, Markus
    Hell, Rüdiger
    Lohmann, Jan U.
    Integration of light and metabolic signals for stem cell activation at the shoot apical meristem2016In: eLIFE, E-ISSN 2050-084X, Vol. 5, article id e17023Article in journal (Refereed)
    Abstract [en]

    A major feature of embryogenesis is the specification of stem cell systems, but in contrast to the situation in most animals, plant stem cells remain quiescent until the postembryonic phase of development. Here, we dissect how light and metabolic signals are integrated to overcome stem cell dormancy at the shoot apical meristem. We show on the one hand that light is able to activate expression of the stem cell inducer WUSCHEL independently of photosynthesis and that this likely involves inter-regional cytokinin signaling. Metabolic signals, on the other hand, are transduced to the meristem through activation of the TARGET OF RAPAMYCIN (TOR) kinase. Surprisingly, TOR is also required for light signal dependent stem cell activation. Thus, the TOR kinase acts as a central integrator of light and metabolic signals and a key regulator of stem cell activation at the shoot apex.

  • 16.
    Pruszynski, J. Andrew
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Department of Physiology and Pharmacology; Department of Psychology; Robarts Research Institute; Brain and Mind Institute, Western University, London, Canada.
    Flanagan, J. Randall
    Johansson, Roland S.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Fast and accurate edge orientation processing during object manipulation2018In: eLIFE, E-ISSN 2050-084X, Vol. 7, article id e31200Article in journal (Refereed)
    Abstract [en]

    Quickly and accurately extracting information about a touched object’s orientation is a critical aspect of dexterous object manipulation. However, the speed and acuity of tactile edge orientation processing with respect to the fingertips as reported in previous perceptual studies appear inadequate in these respects. Here we directly establish the tactile system’s capacity to process edge-orientation information during dexterous manipulation. Participants extracted tactile information about edge orientation very quickly, using it within 200 ms of first touching the object. Participants were also strikingly accurate. With edges spanning the entire fingertip, edge-orientation resolution was better than 3° in our object manipulation task, which is several times better than reported in previous perceptual studies. Performance remained impressive even with edges as short as 2 mm, consistent with our ability to precisely manipulate very small objects. Taken together, our results radically redefine the spatial processing capacity of the tactile system.

  • 17. Reid, Adam J.
    et al.
    Talman, Arthur M.
    Bennett, Hayley M.
    Gomes, Ana R.
    Sanders, Mandy J.
    Illingworth, Christopher J. R.
    Billker, Oliver
    Malaria Programme, Wellcome Sanger Institute, Cambridge, United Kingdom.
    Berriman, Matthew
    Lawniczak, Mara K. N.
    Single-cell RNA-seq reveals hidden transcriptional variation in malaria parasites2018In: eLIFE, E-ISSN 2050-084X, Vol. 7, article id e33105Article in journal (Refereed)
    Abstract [en]

    Single-cell RNA-sequencing is revolutionising our understanding of seemingly homogeneous cell populations but has not yet been widely applied to single-celled organisms. Transcriptional variation in unicellular malaria parasites from the Plasmodium genus is associated with critical phenotypes including red blood cell invasion and immune evasion, yet transcriptional variation at an individual parasite level has not been examined in depth. Here, we describe the adaptation of a single-cell RNA-sequencing (scRNA-seq) protocol to deconvolute transcriptional variation for more than 500 individual parasites of both rodent and human malaria comprising asexual and sexual life-cycle stages. We uncover previously hidden discrete transcriptional signatures during the pathogenic part of the life cycle, suggesting that expression over development is not as continuous as commonly thought. In transmission stages, we find novel, sex-specific roles for differential expression of contingency gene families that are usually associated with immune evasion and pathogenesis.

  • 18. Rozman Grinberg, Inna
    et al.
    Lundin, Daniel
    Hasan, Mahmudul
    Crona, Mikael
    Rao Jonna, Venkateswara
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Loderer, Chrishtoph
    Sahlin, Margareta
    Markova, Natalia
    Borovok, Ilya
    Berggren, Gustav
    Hofer, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Logan, Derek T.
    Sjöberg, Britt-Marie
    Novel ATP-cone-driven allosteric regulation of ribonucleotide reductase via the radical-generating subunit2018In: eLIFE, E-ISSN 2050-084X, Vol. 7, article id e31529Article in journal (Refereed)
    Abstract [en]

    Ribonucleotide reductases (RNRs) are key enzymes in DNA metabolism, with allosteric mechanisms controlling substrate specificity and overall activity. In RNRs, the activity master-switch, the ATP-cone, has been found exclusively in the catalytic subunit. In two class I RNR subclasses whose catalytic subunit lacks the ATP-cone, we discovered ATP-cones in the radical-generating subunit. The ATP-cone in the Leeuwenhoekiella blandensis radical-generating subunit regulates activity via quaternary structure induced by binding of nucleotides. ATP induces enzymatically competent dimers, whereas dATP induces non-productive tetramers, resulting in different holoenzymes. The tetramer forms by interactions between ATP-cones, shown by a 2.45 A crystal structure. We also present evidence for an (MnMnIV)-Mn-III metal center. In summary, lack of an ATP-cone domain in the catalytic subunit was compensated by transfer of the domain to the radical-generating subunit. To our knowledge, this represents the first observation of transfer of an allosteric domain between components of the same enzyme complex.

  • 19. Sato-Hashimoto, Miho
    et al.
    Nozu, Tomomi
    Toriba, Riho
    Horikoshi, Ayano
    Akaike, Miho
    Kawamoto, Kyoko
    Hirose, Ayaka
    Hayashi, Yuriko
    Nagai, Hiromi
    Shimizu, Wakana
    Saiki, Ayaka
    Ishikawa, Tatsuya
    Elhanbly, Ruwaida
    Kotani, Takenori
    Murata, Yoji
    Saito, Yasuyuki
    Naruse, Masae
    Shibasaki, Koji
    Oldenborg, Per-Arne
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Jung, Steffen
    Matozaki, Takashi
    Fukazawa, Yugo
    Ohnishi, Hiroshi
    Microglial SIRP alpha regulates the emergence of CD11c(+) microglia and demyelination damage in white matter2019In: eLIFE, E-ISSN 2050-084X, Vol. 8, article id e42025Article in journal (Refereed)
    Abstract [en]

    A characteristic subset of microglia expressing CD11c appears in response to brain damage. However, the functional role of CD11c(+) microglia, as well as the mechanism of its induction, are poorly understood. Here we report that the genetic ablation of signal regulatory protein alpha (SIRP alpha), a membrane protein, induced the emergence of CD11c(+) microglia in the brain white matter. Mice lacking CD47, a physiological ligand of SIRP alpha, and microglia-specific SIRP alpha-knockout mice exhibited the same phenotype, suggesting that an interaction between microglial SIRP alpha and CD47 on neighbouring cells suppressed the emergence of CD11c(+) microglia. A lack of SIRP alpha did not cause detectable damage to the white matter, but resulted in the increased expression of genes whose expression is characteristic of the repair phase after demyelination. In addition, cuprizone-induced demyelination was alleviated by the microglia-specific ablation of SIRP alpha. Thus, microglial SIRP alpha suppresses the induction of CD11c(+) microglia that have the potential to accelerate the repair of damaged white matter.

  • 20. Spaulding, Caitlin N.
    et al.
    Schreiber, Henry Louis
    Zheng, Weili
    Dodson, Karen W.
    Hazen, Jennie E.
    Conover, Matt S.
    Wang, Fengbin
    Svenmarker, Pontus
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Luna-Rico, Areli
    Francetic, Olivera
    Andersson, Magnus
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Hultgren, Scott
    Egelman, Edward H.
    Functional role of the type 1 pilus rod structure in mediating host-pathogen interactions2018In: eLIFE, E-ISSN 2050-084X, Vol. 7, article id e31662Article in journal (Refereed)
    Abstract [en]

    Uropathogenic E. coli (UPEC), which cause urinary tract infections (UTI), utilize type 1 pili, a chaperone usher pathway (CUP) pilus, to cause UTI and colonize the gut. The pilus rod, comprised of repeating FimA subunits, provides a structural scaffold for displaying the tip adhesin, FimH. We solved the 4.2 Å resolution structure of the type 1 pilus rod using cryo-electron microscopy. Residues forming the interactive surfaces that determine the mechanical properties of the rod were maintained by selection based on a global alignment of fimA sequences. We identified mutations that did not alter pilus production in vitro but reduced the force required to unwind the rod. UPEC expressing these mutant pili were significantly attenuated in bladder infection and intestinal colonization in mice. This study elucidates an unappreciated functional role for the molecular spring-like property of type 1 pilus rods in host-pathogen interactions and carries important implications for other pilus-mediated diseases.

  • 21. Speth, Corinna
    et al.
    Szabo, Emese Xochitl
    Martinho, Claudia
    Collani, Silvio
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    zur Oven-Krockhaus, Sven
    Richter, Sandra
    Droste-Borel, Irina
    Macek, Boris
    Stierhof, York-Dieter
    Schmid, Markus
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Liu, Chang
    Laubinger, Sascha
    Arabidopsis RNA processing factor SERRATE regulates the transcription of intronless genes2018In: eLIFE, E-ISSN 2050-084X, Vol. 7, article id e37078Article in journal (Refereed)
    Abstract [en]

    Intron splicing increases proteome complexity, promotes RNA stability, and enhances transcription. However, introns and the concomitant need for splicing extend the time required for gene expression and can cause an undesirable delay in the activation of genes. Here, we show that the plant microRNA processing factor SERRATE (SE) plays an unexpected and pivotal role in the regulation of intronless genes. Arabidopsis SE associated with more than 1000, mainly intronless, genes in a transcription-dependent manner. Chromatin-bound SE liaised with paused and elongating polymerase II complexes and promoted their association with intronless target genes. Our results indicate that stress-responsive genes contain no or few introns, which negatively affects their expression strength, but that some genes circumvent this limitation via a novel SE-dependent transcriptional activation mechanism. Transcriptome analysis of a Drosophila mutant defective in ARS2, the metazoan homologue of SE, suggests that SE/ARS2 function in regulating intronless genes might be conserved across kingdoms.

  • 22. Yang, Aimin
    et al.
    Pantoom, Supansa
    Wu, Yao-Wen
    Institute of Chemical Biology and Precision Therapy, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China; Chemical Genomics Centre of the Max Planck Society, Dortmund, Germany; Max-Planck-Institute of Molecular Physiology, Dortmund, Germany.
    Elucidation of the anti-autophagy mechanism of the Legionella effector RavZ using semisynthetic LC3 proteins2017In: eLIFE, E-ISSN 2050-084X, Vol. 6, article id e23905Article in journal (Refereed)
    Abstract [en]

    Autophagy is a conserved cellular process involved in the elimination of proteins and organelles. It is also used to combat infection with pathogenic microbes. The intracellular pathogen Legionella pneumophila manipulates autophagy by delivering the effector protein RavZ to deconjugate Atg8/LC3 proteins coupled to phosphatidylethanolamine (PE) on autophagosomal membranes. To understand how RavZ recognizes and deconjugates LC3-PE, we prepared semisynthetic LC3 proteins and elucidated the structures of the RavZ:LC3 interaction. Semisynthetic LC3 proteins allowed the analysis of structure-function relationships. RavZ extracts LC3-PE from the membrane before deconjugation. RavZ initially recognizes the LC3 molecule on membranes via its N-terminal LC3-interacting region (LIR) motif. The RavZ α3 helix is involved in extraction of the PE moiety and docking of the acyl chains into the lipid-binding site of RavZ that is related in structure to that of the phospholipid transfer protein Sec14. Thus, Legionella has evolved a novel mechanism to specifically evade host autophagy.

  • 23. Yeung, Kelvin
    et al.
    Boija, Ann
    Karlsson, Edvin
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Division of CBRN Security and Defence, FOI-Swedish Defence Research Agency, Umeå, Sweden.
    Holmqvist, Per-Henrik
    Tstskis, Yonit
    Nisoli, Ilaria
    Yap, Damian
    Lorzadeh, Alireza
    Moksa, Michelle
    Hirst, Martin
    Aparicio, Samuel
    Fanto, Manolis
    Stenberg, Per
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Division of CBRN Security and Defence, FOI-Swedish Defence Research Agency, Umeå, Sweden.
    Mannervik, Mattias
    McNeill, Helen
    Atrophin controls developmental signaling pathways via interactions with Trithorax-like2017In: eLIFE, E-ISSN 2050-084X, Vol. 6, article id e23084Article in journal (Refereed)
    Abstract [en]

    Mutations in human Atrophin1, a transcriptional corepressor, cause dentatorubral-pallidoluysian atrophy, a neurodegenerative disease. Drosophila Atrophin (Atro) mutants display many phenotypes, including neurodegeneration, segmentation, patterning and planar polarity defects. Despite Atros critical role in development and disease, relatively little is known about Atros binding partners and downstream targets. We present the first genomic analysis of Atro using ChIP-seq against endogenous Atro. ChIP-seq identified 1300 potential direct targets of Atro including engrailed, and components of the Dpp and Notch signaling pathways. We show that Atro regulates Dpp and Notch signaling in larval imaginal discs, at least partially via regulation of thickveins and fringe. In addition, bioinformatics analyses, sequential ChIP and coimmunoprecipitation experiments reveal that Atro interacts with the Drosophila GAGA Factor, Trithorax-like (Trl), and they bind to the same loci simultaneously. Phenotypic analyses of Trl and Atro clones suggest that Atro is required to modulate the transcription activation by Trl in larval imaginal discs. Taken together, these data indicate that Atro is a major Trl cofactor that functions to moderate developmental gene transcription.

  • 24. Zhang, Bo
    et al.
    Holmlund, Mattias
    Lorrain, Severine
    Norberg, Mikael
    Bakó, László
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Fankhauser, Christian
    Nilsson, Ove
    BLADE-ON-PETIOLE proteins act in an E3 ubiquitin ligase complex to regulate PHYTOCHROME INTERACTING FACTOR 4 abundance2017In: eLIFE, E-ISSN 2050-084X, Vol. 6, article id e26759Article in journal (Refereed)
    Abstract [en]

    Both light and temperature have dramatic effects on plant development. Phytochrome photoreceptors regulate plant responses to the environment in large part by controlling the abundance of PHYTOCHROME INTERACTING FACTOR (PIF) transcription factors. However, the molecular determinants of this essential signaling mechanism still remain largely unknown. Here, we present evidence that the BLADE-ON-PETIOLE (BOP) genes, which have previously been shown to control leaf and flower development in Arabidopsis, are involved in controlling the abundance of PIF4. Genetic analysis shows that BOP2 promotes photo-morphogenesis and modulates thermomorphogenesis by suppressing PIF4 activity, through a reduction in PIF4 protein level. In red-light-grown seedlings PIF4 ubiquitination was reduced in the bop2 mutant. Moreover, we found that BOP proteins physically interact with both PIF4 and CULLIN3A and that a CULLIN3-BOP2 complex ubiquitinates PIF4 in vitro. This shows that BOP proteins act as substrate adaptors in a CUL3BOP1/BOP2 E3 ubiquitin ligase complex, targeting PIF4 proteins for ubiquitination and subsequent degradation.

1 - 24 of 24
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