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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 universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Selenko, Philipp
    Musacchio, Andrea
    Maffini, Stefano
    Electroporated recombinant proteins as tools for in vivo functional complementation, imaging and chemical biology2019Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 8, artikel-id e48287Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Laboratory of Genetic Immunology, BioMediTech, University of Tampere, Tampere, Finland.
    Hultmark, Dan
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Laboratory of Genetic Immunology, BioMediTech, University of Tampere, Tampere, Finland.
    New ways to make a blood cell2015Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 4, artikel-id e06877Artikel i tidskrift (Övrigt vetenskapligt)
    Ladda ner fulltext (pdf)
    fulltext
  • 3.
    Bastidas, Robert J.
    et al.
    Department of Integrative Immunobiology, Duke University, Durham, United States.
    Kędzior, Mateusz
    Department of Integrative Immunobiology, Duke University, Durham, United States.
    Davidson, Robert K.
    Department of Molecular Genetics and Microbiology, Duke University, Duke, United States.
    Walsh, Stephen C.
    Department of Molecular Genetics and Microbiology, Duke University, Duke, United States.
    Dolat, Lee
    Department of Integrative Immunobiology, Duke University, Durham, United States.
    Sixt, Barbara Susanne
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Pruneda, Jonathan N.
    Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, United States.
    Coers, Jörn
    Department of Integrative Immunobiology, Duke University, Durham, United States; Department of Molecular Genetics and Microbiology, Duke University, Duke, United States.
    Valdivia, Raphael H.
    Department of Integrative Immunobiology, Duke University, Durham, United States; Department of Molecular Genetics and Microbiology, Duke University, Duke, United States.
    The acetylase activity of Cdu1 regulates bacterial exit from infected cells by protecting Chlamydia effectors from degradation2024Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 12, artikel-id 87386Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Many cellular processes are regulated by ubiquitin-mediated proteasomal degradation. Pathogens can regulate eukaryotic proteolysis through the delivery of proteins with de-ubiquitinating (DUB) activities. The obligate intracellular pathogen Chlamydia trachomatis secretes Cdu1 (ChlaDUB1), a dual deubiquitinase and Lys-acetyltransferase, that promotes Golgi remodeling and survival of infected host cells presumably by regulating the ubiquitination of host and bacterial proteins. Here, we determined that Cdu1's acetylase but not its DUB activity is important to protect Cdu1 from ubiquitin-mediated degradation. We further identified three C. trachomatis proteins on the pathogen-containing vacuole (InaC, IpaM, and CTL0480) that required Cdu1's acetylase activity for protection from degradation and determined that Cdu1 and these Cdu1-protected proteins are required for optimal egress of Chlamydia from host cells. These findings highlight a non-canonical mechanism of pathogen-mediated protection of virulence factors from degradation after their delivery into host cells and the coordinated regulation of secreted effector proteins.

    Ladda ner fulltext (pdf)
    fulltext
  • 4. Bebel, Aleksandra
    et al.
    Walsh, Melissa A.
    Mir-Sanchis, Ignacio
    Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, United States.
    Rice, Phoebe A.
    A novel DNA primase-helicase pair encoded by SCCmec elements2020Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 9, artikel-id e55478Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Mobile genetic elements (MGEs) are a rich source of new enzymes, and conversely, understanding the activities of MGE-encoded proteins can elucidate MGE function. Here, we biochemically characterize three proteins encoded by a conserved operon carried by the Staphylococcal Cassette Chromosome (SCCmec), an MGE that confers methicillin resistance to Staphylococcus aureus, creating MRSA strains. The first of these proteins, CCPol, is an active A-family DNA polymerase. The middle protein, MP, binds tightly to CCPol and confers upon it the ability to synthesize DNA primers de novo. The CCPol-MP complex is therefore a unique primase-polymerase enzyme unrelated to either known primase family. The third protein, Cch2, is a 3'-to-5' helicase. Cch2 additionally binds specifically to a dsDNA sequence downstream of its gene that is also a preferred initiation site for priming by CCPol-MP. Taken together, our results suggest that this is a functional replication module for SCCmec.

    Ladda ner fulltext (pdf)
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  • 5. 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 universitet, Medicinska fakulteten, Institutionen för omvårdnad. 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 universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    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 height2016Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 5, artikel-id e13410Artikel i tidskrift (Refereegranskat)
    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.

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  • 6.
    Billker, Oliver
    Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
    Cracking Ali Baba's code2017Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 6Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

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  • 7.
    Calatayud, Joaquín
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik. Departamento de Biología, Geología, Física y Química inorgánica, Universidad Rey Juan Carlos, Madrid, Spain.
    Neuman, Magnus
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik.
    Rojas, Alexis
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik.
    Eriksson, Anton
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik.
    Rosvall, Martin
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik.
    Regularities in species’ niches reveal the world’s climate regions2021Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 10, artikel-id e58397Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Climate regions form the basis of many ecological, evolutionary, and conservation studies. However, our understanding of climate regions is limited to how they shape vegetation: They do not account for the distribution of animals. Here we develop a network-based framework to identify important climates worldwide based on regularities in realized niches of about 26,000 tetrapods. We show that high-energy climates, including deserts, tropical savannas, and steppes, are consistent across animal-and plant-derived classifications, indicating similar underlying climatic determinants. Conversely, temperate climates differ across all groups, suggesting that these climates allow for idiosyncratic adaptations. Finally, we show how the integration of niche classifications with geographical information enables the detection of climatic transition zones and the signal of geographic and historical processes. Our results identify the climates shaping the distribution of tetrapods and call for caution when using general climate classifications to study the ecology, evolution, or conservation of specific taxa.

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  • 8.
    Chandra, Abel
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för datavetenskap.
    Tünnermann, Laura
    Umeå Plant Science Centre (UPSC), Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Löfstedt, Tommy
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för datavetenskap.
    Gratz, Regina
    Umeå Plant Science Centre (UPSC), Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, Umeå, Sweden; Department of Forest Ecology and Management, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Transformer-based deep learning for predicting protein properties in the life sciences2023Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 12, artikel-id e82819Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Recent developments in deep learning, coupled with an increasing number of sequenced proteins, have led to a breakthrough in life science applications, in particular in protein property prediction. There is hope that deep learning can close the gap between the number of sequenced proteins and proteins with known properties based on lab experiments. Language models from the field of natural language processing have gained popularity for protein property predictions and have led to a new computational revolution in biology, where old prediction results are being improved regularly. Such models can learn useful multipurpose representations of proteins from large open repositories of protein sequences and can be used, for instance, to predict protein properties. The field of natural language processing is growing quickly because of developments in a class of models based on a particular model - the Transformer model. We review recent developments and the use of large-scale Transformer models in applications for predicting protein characteristics and how such models can be used to predict, for example, post-translational modifications. We review shortcomings of other deep learning models and explain how the Transformer models have quickly proven to be a very promising way to unravel information hidden in the sequences of amino acids.

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  • 9.
    Day, Thomas C.
    et al.
    School of Physics, Georgia Institute of Technology, Atlanta, United States.
    Höhn, Stephanie S.
    Department of Applied Mathematics and Theoretical Physics, Centre for Mathematical Sciences, University of Cambridge, Cambridge, United Kingdom.
    Zamani-Dahaj, Seyed A.
    School of Physics, Georgia Institute of Technology, Atlanta, United States; School of Biological Sciences, Georgia Institute of Technology, Atlanta, United States; Quantitative Biosciences Graduate Program, Georgia Institute of Technology, Atlanta, United States.
    Yanni, David
    School of Physics, Georgia Institute of Technology, Atlanta, United States.
    Burnetti, Anthony
    School of Biological Sciences, Georgia Institute of Technology, Atlanta, United States.
    Pentz, Jennifer
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). School of Biological Sciences, Georgia Institute of Technology, Atlanta, United States.
    Honerkamp-Smith, Aurelia R.
    Department of Applied Mathematics and Theoretical Physics, Centre for Mathematical Sciences, University of Cambridge, Cambridge, United Kingdom.
    Wioland, Hugo
    Department of Applied Mathematics and Theoretical Physics, Centre for Mathematical Sciences, University of Cambridge, Cambridge, United Kingdom.
    Sleath, Hannah R.
    Department of Applied Mathematics and Theoretical Physics, Centre for Mathematical Sciences, University of Cambridge, Cambridge, United Kingdom.
    Ratcliff, William C.
    School of Biological Sciences, Georgia Institute of Technology, Atlanta, United States.
    Goldstein, Raymond E.
    Department of Applied Mathematics and Theoretical Physics, Centre for Mathematical Sciences, University of Cambridge, Cambridge, United Kingdom.
    Yunker, Peter J.
    School of Physics, Georgia Institute of Technology, Atlanta, United States.
    Cellular organization in lab-evolved and extant multicellular species obeys a maximum entropy law2022Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 11, artikel-id e72707Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The prevalence of multicellular organisms is due in part to their ability to form complex structures. How cells pack in these structures is a fundamental biophysical issue, underlying their functional properties. However, much remains unknown about how cell packing geometries arise, and how they are affected by random noise during growth - especially absent developmental programs. Here, we quantify the statistics of cellular neighborhoods of two different multicellular eukaryotes: lab-evolved 'snowflake' yeast and the green alga Volvox carteri. We find that despite large differences in cellular organization, the free space associated with individual cells in both organisms closely fits a modified gamma distribution, consistent with maximum entropy predictions originally developed for granular materials. This 'entropic' cellular packing ensures a degree of predictability despite noise, facilitating parent-offspring fidelity even in the absence of developmental regulation. Together with simulations of diverse growth morphologies, these results suggest that gamma-distributed cell neighborhood sizes are a general feature of multicellularity, arising from conserved statistics of cellular packing.

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  • 10. de Boer, Lieke
    et al.
    Axelsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Dayan, Peter
    Backman, Lars
    Guitart-Masip, Marc
    Attenuation of dopamine-modulated prefrontal value signals underlies probabilistic reward learning deficits in old age2017Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 6, artikel-id e2642Artikel i tidskrift (Refereegranskat)
    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.

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  • 11.
    del Peso Santos, Teresa
    et al.
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Alvarez, Laura
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Sit, Brandon
    Howard Hughes Medical Institute, Brigham and Women’s Hospital Division of Infectious Diseases and Harvard Medical School Department of Microbiology and Immunobiology, MA, Boston, United States.
    Irazoki, Oihane
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Blake, Jonathon
    Genomics Core Facility, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
    Warner, Benjamin R.
    Department of Microbiology, The Ohio State University, OH, Columbus, United States; Center for RNA Biology, The Ohio State University, OH, Columbus, United States.
    Warr, Alyson R.
    Howard Hughes Medical Institute, Brigham and Women’s Hospital Division of Infectious Diseases and Harvard Medical School Department of Microbiology and Immunobiology, MA, Boston, United States.
    Bala, Anju
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Benes, Vladimir
    Genomics Core Facility, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
    Waldor, Matthew K.
    Howard Hughes Medical Institute, Brigham and Women’s Hospital Division of Infectious Diseases and Harvard Medical School Department of Microbiology and Immunobiology, MA, Boston, United States.
    Fredrick, Kurt
    Department of Microbiology, The Ohio State University, OH, Columbus, United States; Center for RNA Biology, The Ohio State University, OH, Columbus, United States.
    Cava, Felipe
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    BipA exerts temperature-dependent translational control of biofilm-associated colony morphology in Vibrio cholerae2021Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 10, artikel-id e60607Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Adaptation to shifting temperatures is crucial for the survival of the bacterial pathogen Vibrio cholerae. Here, we show that colony rugosity, a biofilm-associated phenotype, is regulated by temperature in V. cholerae strains that naturally lack the master biofilm transcriptional regulator HapR. Using transposon-insertion mutagenesis, we found the V. cholerae ortholog of BipA, a conserved ribosome-associated GTPase, is critical for this temperature-dependent phenomenon. Proteomic analyses revealed that loss of BipA alters the synthesis of >300 proteins in V. cholerae at 22˚C, increasing the production of biofilm-related proteins including the key transcriptional activators VpsR and VpsT, as well as proteins important for diverse cellular processes. At low temperatures, BipA protein levels increase and are required for optimal ribosome assembly in V. cholerae, suggesting that control of BipA abundance is a mechanism by which bacteria can remodel their proteomes. Our study reveals a remarkable new facet of V. cholerae’s complex biofilm regulatory network.

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  • 12.
    Delhaye, Benoit P.
    et al.
    Institute of Information and Communication Technologies, Electronics and Applied Mathematics, Université catholique de Louvain, Louvain-la-Neuve, Belgium; Institute of Neuroscience, Université catholique de Louvain, Brussels, Belgium.
    Jarocka, Ewa
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Barrea, Allan
    Institute of Information and Communication Technologies, Electronics and Applied Mathematics, Université catholique de Louvain, Louvain-la-Neuve, Belgium; Institute of Neuroscience, Université catholique de Louvain, Brussels, Belgium.
    Thonnard, Jean-Louis
    Institute of Information and Communication Technologies, Electronics and Applied Mathematics, Université catholique de Louvain, Louvain-la-Neuve, Belgium; Institute of Neuroscience, Université catholique de Louvain, Brussels, Belgium.
    Edin, Benoni B.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Lefèvre, Philippe
    Institute of Information and Communication Technologies, Electronics and Applied Mathematics, Université catholique de Louvain, Louvain-la-Neuve, Belgium; Institute of Neuroscience, Université catholique de Louvain, Brussels, Belgium.
    High-resolution imaging of skin deformation shows that afferents from human fingertips signal slip onset2021Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 10, artikel-id e64679Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Human tactile afferents provide essential feedback for grasp stability during dexterous object manipulation. Interacting forces between an object and the fingers induce slip events that are thought to provide information about grasp stability. To gain insight into this phenomenon, we made a transparent surface slip against a fixed fingerpad while monitoring skin deformation at the contact. Using microneurography, we simultaneously recorded the activity of single tactile afferents innervating the fingertips. This unique combination allowed us to describe how afferents respond to slip events and to relate their responses to surface deformations taking place inside their receptive fields. We found that all afferents were sensitive to slip events, but FA-I afferents in particular faithfully encoded compressive strain rates resulting from those slips. Given the high density of FA-I afferents in fingerpads, they are well suited to detect incipient slips and to provide essential information for the control of grip force during manipulation.

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  • 13. 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 universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Rensen, Patrick C. N.
    Heeren, Joerg
    Kersten, Sander
    ANGPTL4 mediates shuttling of lipid fuel to brown adipose tissue during sustained cold exposure2015Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 4, artikel-id e08428Artikel i tidskrift (Refereegranskat)
    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.

  • 14.
    Dimitriou, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Human muscle spindles are wired to function as controllable signal-processing devices2022Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 11, artikel-id e78091Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Muscle spindles are encapsulated sensory organs found in most of our muscles. Prevalent models of sensorimotor control assume the role of spindles is to reliably encode limb posture and movement. Here, I argue that the traditional view of spindles is outdated. Spindle organs can be tuned by spinal γ motor neurons that receive top-down and peripheral input, including from cutaneous afferents. A new model is presented, viewing γ motor activity as an intermediate coordinate transformation that allows multimodal information to converge on spindles, creating flexible coordinate representations at the level of the peripheral nervous system. That is, I propose that spindles play a unique overarching role in the nervous system: that of a peripheral signal-processing device that flexibly facilitates sensorimotor performance, according to task characteristics. This role is compatible with previous findings and supported by recent studies with naturalistically active humans. Such studies have so far shown that spindle tuning enables the independent preparatory control of reflex muscle stiffness, the selective extraction of information during implicit motor adaptation, and for segmental stretch reflexes to operate in joint space. Incorporation of advanced signal-processing at the periphery may well prove a critical step in the evolution of sensorimotor control theories.

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  • 15.
    Fjell, Anders M.
    et al.
    Research Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Norway; Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
    Grydeland, Håkon
    Research Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Norway.
    Wang, Yunpeng
    Research Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Norway.
    Amlien, Inge
    Research Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Norway.
    Bartrés-Faz, David
    Departament de Medicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, and Institut de Neurociències, Universitat de Barcelona, Spain.
    Brandmaier, Andreas M.
    Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany; Max Planck, UCL Centre for Computational Psychiatry and Ageing Research, Berlin, Germany; Max Planck, UCL Centre for Computational Psychiatry and Ageing Research, London, United Kingdom.
    Düzel, Sandra
    Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany.
    Elman, Jeremy
    Center for Behavioral Genomics Twin Research Laboratory, University of California, La Jolla, CA, San Diego, United States; Department of Psychiatry, University of California, La Jolla, San Diego, United States.
    Franz, Carol
    Center for Behavioral Genomics Twin Research Laboratory, University of California, La Jolla, CA, San Diego, United States; Department of Psychiatry, University of California, La Jolla, San Diego, United States.
    Håberg, Asta K.
    Department of Medical Imaging, St. Olav's Hospital, Trondheim, Norway; Department of Neuroscience, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
    Kietzmann, Tim C.
    MRC Cognition and Brain Sciences Unit, University of Cambridge, United Kingdom; Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, Netherlands.
    Kievit, Rogier A.
    MRC Cognition and Brain Sciences Unit, University of Cambridge, United Kingdom.
    Kremen, William S.
    Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, La Jolla, CA, United States; Center for Behavioral Genomics Twin Research Laboratory, University of California, La Jolla, CA, San Diego, United States; Department of Psychiatry, University of California, La Jolla, San Diego, United States.
    Krogsrud, Stine K.
    Research Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Norway.
    Kühn, Simone
    Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany; Lise Meitner Group for Environmental Neuroscience, Max Planck Institute for Human Development, Berlin, Germany.
    Lindenberger, Ulman
    Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany; Max Planck, UCL Centre for Computational Psychiatry and Ageing Research, Berlin, Germany; Max Planck, UCL Centre for Computational Psychiatry and Ageing Research, London, United Kingdom.
    Macià, Didac
    Departament de Medicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, and Institut de Neurociències, Universitat de Barcelona, Spain.
    Mowinckel, Athanasia M.
    Research Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Norway.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway.
    Panizzon, Matthew S.
    Center for Behavioral Genomics Twin Research Laboratory, University of California, La Jolla, CA, San Diego, United States; Department of Psychiatry, University of California, La Jolla, San Diego, United States.
    Solé-Padullés, Cristina
    Departament de Medicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, and Institut de Neurociències, Universitat de Barcelona, Spain.
    Sørensen, Øystein
    Research Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Norway.
    Westerhausen, René
    Research Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Norway.
    Walhovd, Kristine B.
    Research Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Norway; Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
    The genetic organization of longitudinal subcortical volumetric change is stable throughout the lifespan running title: Genetics of subcortical lifespan change2021Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 10, artikel-id e66466Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Development and aging of the cerebral cortex show similar topographic organization and are governed by the same genes. It is unclear whether the same is true for subcortical regions, which follow fundamentally different ontogenetic and phylogenetic principles. We tested the hypothesis that genetically governed neurodevelopmental processes can be traced throughout life by assessing to which degree brain regions that develop together continue to change together through life. Analyzing over 6000 longitudinal MRIs of the brain, we used graph theory to identify five clusters of coordinated development, indexed as patterns of correlated volumetric change in brain structures. The clusters tended to follow placement along the cranial axis in embryonic brain development, suggesting continuity from prenatal stages, and correlated with cognition. Across independent longitudinal datasets, we demonstrated that developmental clusters were conserved through life. Twin-based genetic correlations revealed distinct sets of genes governing change in each cluster. Single nucleotide polymorphisms-based analyses of 38127 cross-sectional MRIs showed a similar pattern of genetic volume-volume correlations. In conclusion, coordination of subcortical change adheres to fundamental principles of lifespan continuity and genetic organization.

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  • 16.
    Godbersen, Godber M.
    et al.
    Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria; Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria.
    Klug, Sebastian
    Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria; Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria.
    Wadsak, Wolfgang
    Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria; Center for Biomarker Research in Medicine (CBmed), Graz, Austria.
    Pichler, Verena
    Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria; Department of Pharmaceutical Sciences, Division of Pharmaceutical Chemistry, University of Vienna, Vienna, Austria.
    Raitanen, Julia
    Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Institute Applied Diagnostics, Vienna, Austria; Department of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria.
    Rieckmann, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Munich Center for the Economics of Aging, Max Planck Institute for Social Law and Social Policy, Munich, Germany.
    Stiernman, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Cocchi, Luca
    Clinical Brain Networks Group, QIMR Berghofer Medical Research Institute, Brisbane, Australia; School of Biomedical Sciences, Faculty of Medicine, University of Queensland, Brisbane, Australia.
    Breakspear, Michael
    School of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, Australia; School of Psychological Sciences, College of Engineering, Science and Environment, University of Newcastle, Callaghan, Australia.
    Hacker, Marcus
    Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria.
    Lanzenberger, Rupert
    Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria; Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria.
    Hahn, Andreas
    Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria; Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria.
    Task-evoked metabolic demands of the posteromedial default mode network are shaped by dorsal attention and frontoparietal control networks2023Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 12, artikel-id e84683Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    External tasks evoke characteristic fMRI BOLD signal deactivations in the default mode network (DMN). However, for the corresponding metabolic glucose demands both decreases and increases have been reported. To resolve this discrepancy, functional PET/MRI data from 50 healthy subjects performing Tetris were combined with previously published data sets of working memory, visual and motor stimulation. We show that the glucose metabolism of the posteromedial DMN is dependent on the metabolic demands of the correspondingly engaged task-positive networks. Specifically, the dorsal attention and frontoparietal network shape the glucose metabolism of the posteromedial DMN in opposing directions. While tasks that mainly require an external focus of attention lead to a consistent downregulation of both metabolism and the BOLD signal in the posteromedial DMN, cognitive control during working memory requires a metabolically expensive BOLD suppression. This indicates that two types of BOLD deactivations with different oxygen-to-glucose index may occur in this region. We further speculate that consistent downregulation of the two signals is mediated by decreased glutamate signaling, while divergence may be subject to active GABAergic inhibition. The results demonstrate that the DMN relates to cognitive processing in a flexible manner and does not always act as a cohesive task-negative network in isolation.

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  • 17.
    Grønberg, Christina
    et al.
    Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen N, Denmark.
    Hu, Qiaoxia
    Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen N, Denmark.
    Mahato, Dhani Ram
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Longhin, Elena
    Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen N, Denmark.
    Salustros, Nina
    Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen N, Denmark.
    Duelli, Annette
    Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen N, Denmark.
    Lyu, Pin
    Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen N, Denmark.
    Bågenholm, Viktoria
    Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen N, Denmark.
    Eriksson, Jonas
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Rao, Komal Umashankar
    Department of Laboratory Medicine, Lund University, Klinikgatan 28, Lund, Sweden.
    Henderson, Domhnall Iain
    Department of Laboratory Medicine, Lund University, Klinikgatan 28, Lund, Sweden.
    Meloni, Gabriele
    Department of Chemistry and Biochemistry, The University of Texas at Dallas, 800 W Campbell Rd., TX, Richardson, United States.
    Andersson, Magnus
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Croll, Tristan
    Cambridge Institute for Medical Research, Department of Haematology, University of Cambridge, Keith Peters Building, Hills Rd, Cambridge, United Kingdom.
    Godaly, Gabriela
    Department of Laboratory Medicine, Lund University, Klinikgatan 28, Lund, Sweden.
    Wang, Kaituo
    Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen N, Denmark.
    Gourdon, Pontus
    Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen N, Denmark; Department of Experimental Medical Science, Lund University, Sölvegatan 19, Lund, Sweden.
    Structure and ion-release mechanism of PIB-4-type ATPases2021Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 10, artikel-id e73124Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Transition metals, such as zinc, are essential micronutrients in all organisms, but also highly toxic in excessive amounts. Heavy-metal transporting P-type (PIB) ATPases are crucial for homeostasis, conferring cellular detoxification and redistribution through transport of these ions across cellular membranes. No structural information is available for the PIB-4-ATPases, the subclass with the broadest cargo scope, and hence even their topology remains elusive. Here we present structures and complementary functional analyses of an archetypal PIB-4-ATPase, sCoaT from Sulfitobacter sp. NAS14-1. The data disclose the architecture, devoid of classical so-called heavy metal binding domains, and provides fundamentally new insights into the mechanism and diversity of heavy metal transporters. We reveal several novel P-type ATPase features, including a dual role in heavy-metal release and as an internal counter ion of an invariant Page 2 histidine. We also establish that the turn-over of PIB-ATPases is potassium independent, contrasting to many other P-type ATPases. Combined with new inhibitory compounds, our results open up for efforts in e.g. drug discovery, since PIB-4-ATPases function as virulence factors in many pathogens.

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  • 18. 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 kinase2015Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 4, artikel-id e09811Artikel i tidskrift (Refereegranskat)
    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.

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  • 19. Hannon, Eilis
    et al.
    Dempster, Emma L.
    Mansell, Georgina
    Burrage, Joe
    Bass, Nick
    Bohlken, Marc M.
    Corvin, Aiden
    Curtis, Charles J.
    Dempster, David
    Di Forti, Marta
    Dinan, Timothy G.
    Donohoe, Gary
    Gaughran, Fiona
    Gill, Michael
    Gillespie, Amy
    Gunasinghe, Cerisse
    Hulshoff, Hilleke E.
    Hultman, Christina M.
    Johansson, Viktoria
    Department of Medical Epidemiology and Biostatistics Sweden, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institutet and Stockholm Health Care Services, Stockholm, Sweden.
    Kahn, René S.
    Kaprio, Jaakko
    Kenis, Gunter
    Kowalec, Kaarina
    MacCabe, James
    McDonald, Colm
    McQuillin, Andrew
    Morris, Derek W.
    Murphy, Kieran C.
    Mustard, Colette J.
    Nenadic, Igor
    O'Donovan, Michael C.
    Quattrone, Diego
    Richards, Alexander L.
    Rutten, Bart P.F.
    St Clair, David
    Therman, Sebastian
    Toulopoulou, Timothea
    Van Os, Jim
    Waddington, John L.
    Sullivan, Patrick
    Vassos, Evangelos
    Breen, Gerome
    Collier, David Andrew
    Murray, Robin M.
    Schalkwyk, Leonard S.
    Mill, Jonathan
    DNA methylation meta-analysis reveals cellular alterations in psychosis and markers of treatment-resistant schizophrenia2021Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 10, artikel-id e58430Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We performed a systematic analysis of blood DNA methylation profiles from 4483 participants from seven independent cohorts identifying differentially methylated positions (DMPs) associated with psychosis, schizophrenia, and treatment-resistant schizophrenia. Psychosis cases were characterized by significant differences in measures of blood cell proportions and elevated smoking exposure derived from the DNA methylation data, with the largest differences seen in treatment-resistant schizophrenia patients. We implemented a stringent pipeline to meta-analyze epigenome-wide association study (EWAS) results across datasets, identifying 95 DMPs associated with psychosis and 1048 DMPs associated with schizophrenia, with evidence of colocalization to regions nominated by genetic association studies of disease. Many schizophrenia-associated DNA methylation differences were only present in patients with treatment-resistant schizophrenia, potentially reflecting exposure to the atypical antipsychotic clozapine. Our results highlight how DNA methylation data can be leveraged to identify physiological (e.g., differential cell counts) and environmental (e.g., smoking) factors associated with psychosis and molecular biomarkers of treatment-resistant schizophrenia.

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  • 20.
    Hubert, Madlen
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Larsson, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Vegesna, Naga Venkata Gayathri
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Ahnlund, Maria
    Johansson, Annika I.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Moodie, Lindon W. K.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Lundmark, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Lipid accumulation controls the balance between surface connection and scission of caveolae2020Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 9, artikel-id e55038Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Caveolae are bulb-shaped invaginations of the plasma membrane (PM) that undergo scission and fusion at the cell surface and are enriched in specific lipids. However, the influence of lipid composition on caveolae surface stability is not well described or understood. Accordingly, we inserted specific lipids into the cell PM via membrane fusion and studied their acute effects on caveolae dynamics. We demonstrate that sphingomyelin stabilizes caveolae to the cell surface, whereas cholesterol and glycosphingolipids drive caveolae scission from the PM. Although all three lipids accumulated specifically in caveolae, cholesterol and sphingomyelin were actively sequestered, whereas glycosphingolipids diffused freely. The ATPase EHD2 restricts lipid diffusion and counteracts lipid-induced scission. We propose that specific lipid accumulation in caveolae generates an intrinsically unstable domain prone to scission if not restrained by EHD2 at the caveolae neck. This work provides a mechanistic link between caveolae and their ability to sense the PM lipid composition.

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  • 21.
    Hultmark, Dan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Andó, István
    Biological Research Centre, Institute of Genetics, Innate Immunity Group, Eötvös Loránd Research Network, Szeged, Hungary.
    Hematopoietic plasticity mapped in Drosophila and other insects2022Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 11Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Hemocytes, similar to vertebrate blood cells, play important roles in insect development and immunity, but it is not well understood how they perform their tasks. New technology, in particular single-cell transcriptomic analysis in combination with Drosophila genetics, may now change this picture. This review aims to make sense of recently published data, focusing on Drosophila melanogaster and comparing to data from other drosophilids, the malaria mosquito, Anopheles gambiae, and the silkworm, Bombyx mori. Basically, the new data support the presence of a few major classes of hemocytes: (1) a highly heterogenous and plastic class of professional phagocytes with many functions, called plasmatocytes in Drosophila and granular cells in other insects. (2) A conserved class of cells that control melanin deposition around parasites and wounds, called crystal cells in D. melanogaster, and oenocytoids in other insects. (3) A new class of cells, the primocytes, so far only identified in D. melanogaster. They are related to cells of the so-called posterior signaling center of the larval hematopoietic organ, which controls the hematopoiesis of other hemocytes. (4) Different kinds of specialized cells, like the lamellocytes in D. melanogaster, for the encapsulation of parasites. These cells undergo rapid evolution, and the homology relationships between such cells in different insects are uncertain. Lists of genes expressed in the different hemocyte classes now provide a solid ground for further investigation of function.

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  • 22. Iurilli, Maria LC
    et al.
    Forsner, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Nordendahl, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Filippi, Sarah
    Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight2021Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 10, artikel-id e60060Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.

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  • 23. Laurent, Patrick
    et al.
    Soltesz, Zoltan
    Nelson, Geoffrey M.
    Chen, Changchun
    Laboratory of Molecular Biology, Cambridge, United Kingdom..
    Arellano-Carbajal, Fausto
    Levy, Emmanuel
    de Bono, Mario
    Decoding a neural circuit controlling global animal state in C. elegans.2015Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 4, artikel-id e04241Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Brains organize behavior and physiology to optimize the response to threats or opportunities. We dissect how 21% O2, an indicator of surface exposure, reprograms C. elegans' global state, inducing sustained locomotory arousal and altering expression of neuropeptides, metabolic enzymes, and other non-neural genes. The URX O2-sensing neurons drive arousal at 21% O2 by tonically activating the RMG interneurons. Stimulating RMG is sufficient to switch behavioral state. Ablating the ASH, ADL, or ASK sensory neurons connected to RMG by gap junctions does not disrupt arousal. However, disrupting cation currents in these neurons curtails RMG neurosecretion and arousal. RMG signals high O2 by peptidergic secretion. Neuropeptide reporters reveal neural circuit state, as neurosecretion stimulates neuropeptide expression. Neural imaging in unrestrained animals shows that URX and RMG encode O2 concentration rather than behavior, while the activity of downstream interneurons such as AVB and AIY reflect both O2 levels and the behavior being executed.

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  • 24.
    Laurent, Timothée
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Kumar, Pravin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Liese, Susanne
    Max Planck Institute for the Physics of Complex Systems, Dresden, Germany; Department of Mathematics, Mechanics Division, University of Oslo, Oslo, Norway.
    Zare, Farnaz
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Jonasson, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Carlson, Andreas
    Department of Mathematics, Mechanics Division, University of Oslo, Oslo, Norway.
    Carlson, Lars-Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Architecture of the chikungunya virus replication organelle2022Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 11, artikel-id e83042Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Alphaviruses are mosquito-borne viruses that cause serious disease in humans and other mammals. Along with its mosquito vector, the Alphavirus chikungunya virus (CHIKV) has spread explosively in the last 20 years, and there is no approved treatment for chikungunya fever. On the plasma membrane of the infected cell, CHIKV generates dedicated organelles for viral RNA replication, so-called spherules. Whereas structures exist for several viral proteins that make up the spherule, the architecture of the full organelle is unknown. Here, we use cryo-electron tomography to image CHIKV spherules in their cellular context. This reveals that the viral protein nsP1 serves as a base for the assembly of a larger protein complex at the neck of the membrane bud. Biochemical assays show that the viral helicase-protease nsP2, while having no membrane affinity on its own, is recruited to membranes by nsP1. The tomograms further reveal that full-sized spherules contain a single copy of the viral genome in double-stranded form. Finally, we present a mathematical model that explains the membrane remodeling of the spherule in terms of the pressure exerted on the membrane by the polymerizing RNA, which provides a good agreement with the experimental data. The energy released by RNA polymerization is found to be sufficient to remodel the membrane to the characteristic spherule shape.

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  • 25.
    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 pathways2015Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 4, artikel-id e07074Artikel i tidskrift (Refereegranskat)
    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.

  • 26.
    Lind, Peter A
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet). New Zealand Institute for Advanced Study, Massey University at Albany, Auckland, New Zealand.
    Libby, Eric
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik. 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 phenotypes2019Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 8, s. 1-31, artikel-id e38822Artikel i tidskrift (Refereegranskat)
    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.

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  • 27. 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 infection2015Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 4, artikel-id e05397Artikel i tidskrift (Refereegranskat)
    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.

  • 28.
    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 universitet, Teknisk-naturvetenskapliga fakulteten, 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 plants2015Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 4, artikel-id e05828Artikel i tidskrift (Refereegranskat)
    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.

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  • 29.
    Mediavilla, Tomás
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Özalay, Özgun
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Estévez-Silva, Héctor M.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Frias, Barbara
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Orädd, Greger
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Sultan, Fahad R.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Brozzoli, Claudio
    IMPACT, Centre de Recherche en Neurosciences de Lyon, Lyon, France; Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Solna, Sweden.
    Garzón, Benjamín
    Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Solna, Sweden; Department of Psychology, University of Gothenburg, Gothenburg, Sweden.
    Lövdén, Martin
    Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Solna, Sweden; Department of Psychology, University of Gothenburg, Gothenburg, Sweden.
    Marcellino, Daniel J.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Learning-related contraction of gray matter in rodent sensorimotor cortex is associated with adaptive myelination2022Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 11, artikel-id e77432Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    From observations in rodents, it has been suggested that the cellular basis of learning-dependent changes, detected using structural MRI, may be increased dendritic spine density, alterations in astrocyte volume, and adaptations within intracortical myelin. Myelin plasticity is crucial for neurological function, and active myelination is required for learning and memory. However, the dynamics of myelin plasticity and how it relates to morphometric-based measurements of structural plasticity remains unknown. We used a motor skill learning paradigm in male mice to evaluate experience-dependent brain plasticity by voxel-based morphometry (VBM) in longitudinal MRI, combined with a cross-sectional immunohistochemical investigation. Whole-brain VBM revealed nonlinear decreases in gray matter volume (GMV) juxtaposed to nonlinear increases in white matter volume (WMV) within GM that were best modeled by an asymptotic time course. Using an atlas-based cortical mask, we found nonlinear changes with learning in primary and secondary motor areas and in somatosensory cortex. Analysis of cross-sectional myelin immunoreactivity in forelimb somatosensory cortex confirmed an increase in myelin immunoreactivity followed by a return towards baseline levels. Further investigations using quantitative confocal microscopy confirmed these changes specifically to the length density of myelinated axons. The absence of significant histological changes in cortical thickness suggests that nonlinear morphometric changes are likely due to changes in intracortical myelin for which morphometric WMV in somatosensory cortex significantly correlated with myelin immunoreactivity. Together, these observations indicate a nonlinear increase of intracortical myelin during learning and support the hypothesis that myelin is a component of structural changes observed by VBM during learning.

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  • 30. Mysling, Simon
    et al.
    Kolby Kristensen, Kristian
    Larsson, Mikael
    Kovrov, Oleg
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Bensadouen, André
    Jorgensen, Thomas J. D.
    Olivecrona, Gunilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    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 unfolding2016Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 5, artikel-id e20958Artikel i tidskrift (Refereegranskat)
    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.

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  • 31.
    Nadeem, Aftab
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Berg, Alexandra
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Pace, Hudson
    Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Alam, Athar
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Toh, Eric
    Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Ådén, Jörgen
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Zlatkov, Nikola
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Myint, Si Lhyam
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Persson, Karina
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Gröbner, Gerhard
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Sjöstedt, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Bally, Marta
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Barandun, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Uhlin, Bernt Eric
    Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Wai, Sun Nyunt
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Protein-lipid interaction at low pH induces oligomerization of the MakA cytotoxin from Vibrio cholerae2022Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 11, artikel-id e73439Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The α-pore-forming toxins (α-PFTs) from pathogenic bacteria damage host cell membranes by pore formation. We demonstrate a remarkable, hitherto unknown mechanism by an α-PFT protein from Vibrio cholerae. As part of the MakA/B/E tripartite toxin, MakA is involved in membrane pore formation similar to other α-PFTs. In contrast, MakA in isolation induces tube-like structures in acidic endosomal compartments of epithelial cells in vitro. The present study unravels the dynamics of tubular growth, which occurs in a pH-, lipid-, and concentration-dependent manner. Within acidified organelle lumens or when incubated with cells in acidic media, MakA forms oligomers and remodels membranes into high-curvature tubes leading to loss of membrane integrity. A 3.7 Å cryo-electron microscopy structure of MakA filaments reveals a unique protein-lipid superstructure. MakA forms a pinecone-like spiral with a central cavity and a thin annular lipid bilayer embedded between the MakA transmembrane helices in its active α-PFT conformation. Our study provides insights into a novel tubulation mechanism of an α-PFT protein and a new mode of action by a secreted bacterial toxin.

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  • 32.
    Nyberg, Lars
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    The many facets of brain aging2020Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 9, artikel-id e56640Artikel i tidskrift (Övrigt vetenskapligt)
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    fulltext
  • 33.
    Näsström, Elin
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Parry, Christopher M.
    Thieu, Nga Tran Vu
    Maude, Rapeephan R.
    de Jong, Hanna K.
    Fukushima, Masako
    Rzhepishevska, Olena
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Marks, Florian
    Panzner, Ursula
    Im, Justin
    Jeon, Hyonjin
    Park, Seeun
    Chaudhury, Zabeen
    Ghose, Aniruddha
    Samad, Rasheda
    Van, Tan Trinh
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Dondorp, Arjen M.
    Thwaites, Guy E.
    Faiz, Abul
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Baker, Stephen
    Reproducible diagnostic metabolites in plasma from typhoid fever patients in Asia and Africa2017Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 6, artikel-id e15651Artikel i tidskrift (Refereegranskat)
    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.

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  • 34.
    Näsström, Elin
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Thieu, Nga Tran Vu
    Dongol, Sabina
    Karkey, Abhilasha
    Vinh, Phat Voong
    Thanh, Tuyen Ha
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Arjyal, Amit
    Thwaites, Guy
    Dolecek, Christiane
    Basnyat, Buddha
    Baker, Stephen
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Salmonella Typhi and Salmonella Paratyphi A elaborate distinct systemic metabolite signatures during enteric fever2014Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 3, artikel-id e03100Artikel i tidskrift (Refereegranskat)
    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.

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  • 35.
    Pentz, Jennifer T.
    et al.
    Los Alamos National Laboratory, Los Alamos, United States.
    MacGillivray, Kathryn
    School of Biological Sciences, Georgia Institute of Technology, Atlanta, United States; Interdisciplinary Graduate Program in Quantitative Biosciences, Georgia Institute of Technology, Atlanta, United States.
    DuBose, James G.
    School of Biological Sciences, Georgia Institute of Technology, Atlanta, United States.
    Conlin, Peter L.
    School of Biological Sciences, Georgia Institute of Technology, Atlanta, United States.
    Reinhardt, Emma
    Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, United States.
    Libby, Eric
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik.
    Ratcliff, William C.
    School of Biological Sciences, Georgia Institute of Technology, Atlanta, United States.
    Evolutionary consequences of nascent multicellular life cycles2023Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 12, artikel-id e84336Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A key step in the evolutionary transition to multicellularity is the origin of multicellular groups as biological individuals capable of adaptation. Comparative work, supported by theory, suggests clonal development should facilitate this transition, although this hypothesis has never been tested in a single model system. We evolved 20 replicate populations of otherwise isogenic clonally reproducing 'snowflake' yeast (Δace2/∆ace2) and aggregative 'floc' yeast (GAL1p::FLO1 /GAL1p::FLO1) with daily selection for rapid growth in liquid media, which favors faster cell division, followed by selection for rapid sedimentation, which favors larger multicellular groups. While both genotypes adapted to this regime, growing faster and having higher survival during the group-selection phase, there was a stark difference in evolutionary dynamics. Aggregative floc yeast obtained nearly all their increased fitness from faster growth, not improved group survival; indicating that selection acted primarily at the level of cells. In contrast, clonal snowflake yeast mainly benefited from higher group-dependent fitness, indicating a shift in the level of Darwinian individuality from cells to groups. Through genome sequencing and mathematical modeling, we show that the genetic bottlenecks in a clonal life cycle also drive much higher rates of genetic drift-a result with complex implications for this evolutionary transition. Our results highlight the central role that early multicellular life cycles play in the process of multicellular adaptation.

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  • 36. 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 meristem2016Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 5, artikel-id e17023Artikel i tidskrift (Refereegranskat)
    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.

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  • 37.
    Pruszynski, J. Andrew
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (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 universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Fast and accurate edge orientation processing during object manipulation2018Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 7, artikel-id e31200Artikel i tidskrift (Refereegranskat)
    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.

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  • 38. 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 parasites2018Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 7, artikel-id e33105Artikel i tidskrift (Refereegranskat)
    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.

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  • 39. Rozman Grinberg, Inna
    et al.
    Lundin, Daniel
    Hasan, Mahmudul
    Crona, Mikael
    Rao Jonna, Venkateswara
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Loderer, Chrishtoph
    Sahlin, Margareta
    Markova, Natalia
    Borovok, Ilya
    Berggren, Gustav
    Hofer, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Logan, Derek T.
    Sjöberg, Britt-Marie
    Novel ATP-cone-driven allosteric regulation of ribonucleotide reductase via the radical-generating subunit2018Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 7, artikel-id e31529Artikel i tidskrift (Refereegranskat)
    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.

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  • 40. 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 universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Jung, Steffen
    Matozaki, Takashi
    Fukazawa, Yugo
    Ohnishi, Hiroshi
    Microglial SIRP alpha regulates the emergence of CD11c(+) microglia and demyelination damage in white matter2019Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 8, artikel-id e42025Artikel i tidskrift (Refereegranskat)
    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.

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  • 41. Spaulding, Caitlin N.
    et al.
    Schreiber, Henry Louis
    Zheng, Weili
    Dodson, Karen W.
    Hazen, Jennie E.
    Conover, Matt S.
    Wang, Fengbin
    Svenmarker, Pontus
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik.
    Luna-Rico, Areli
    Francetic, Olivera
    Andersson, Magnus
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik.
    Hultgren, Scott
    Egelman, Edward H.
    Functional role of the type 1 pilus rod structure in mediating host-pathogen interactions2018Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 7, artikel-id e31662Artikel i tidskrift (Refereegranskat)
    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.

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  • 42. Speth, Corinna
    et al.
    Szabo, Emese Xochitl
    Martinho, Claudia
    Collani, Silvio
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik.
    zur Oven-Krockhaus, Sven
    Richter, Sandra
    Droste-Borel, Irina
    Macek, Boris
    Stierhof, York-Dieter
    Schmid, Markus
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik.
    Liu, Chang
    Laubinger, Sascha
    Arabidopsis RNA processing factor SERRATE regulates the transcription of intronless genes2018Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 7, artikel-id e37078Artikel i tidskrift (Refereegranskat)
    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.

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  • 43.
    Sukumar, Vaishnavi
    et al.
    Neuroscience Graduate Program, Western University, London, Canada.
    Johansson, Roland S.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Pruszynski, J. Andrew
    Department of Physiology and Pharmacology, Western University, London, Canada.
    Precise and stable edge orientation signaling by human first-order tactile neurons2022Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 11, artikel-id e81476Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Fast-adapting type 1 (FA-1) and slow-adapting type 1 (SA-1) first-order neurons in the human tactile system have distal axons that branch in the skin and form many transduction sites, yielding receptive fields with many highly sensitive zones or ‘subfields.’ We previously demonstrated that this arrangement allows FA-1 and SA-1 neurons to signal the geometric features of touched objects, specifically the orientation of raised edges scanned with the fingertips. Here, we show that such signaling operates for fine edge orientation differences (5–20°) and is stable across a broad range of scanning speeds (15–180 mm/s); that is, under conditions relevant for real-world hand use. We found that both FA-1 and SA-1 neurons weakly signal fine edge orientation differences via the intensity of their spiking responses and only when considering a single scanning speed. Both neuron types showed much stronger edge orientation signaling in the sequential structure of the evoked spike trains, and FA-1 neurons performed better than SA-1 neurons. Represented in the spatial domain, the sequential structure was strikingly invariant across scanning speeds, especially those naturally used in tactile spatial discrimination tasks. This speed invariance suggests that neurons’ responses are structured via sequential stimulation of their subfields and thus links this capacity to their terminal organization in the skin. Indeed, the spatial precision of elicited action potentials ratio-nally matched spatial acuity of subfield arrangements, which corresponds to a spatial period similar to the dimensions of individual fingertip ridges.

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  • 44.
    Sun, Wei-Sheng
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Lassinantti, Lena
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Järvå, Michael A.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Schmitt, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    ter Beek, Josy
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Berntsson, Ronnie
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Structural foundation for the role of enterococcal PrgB in conjugation, biofilm formation, and virulence2023Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 12Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Type 4 Secretion Systems are a main driver for the spread of antibiotic resistance genes and virulence factors in bacteria. In Gram-positives, these secretion systems often rely on surface adhesins to enhance cellular aggregation and mating-pair formation. One of the best studied adhesins is PrgB from the conjugative plasmid pCF10 of Enterococcus faecalis, which has been shown to play major roles in conjugation, biofilm formation, and importantly also in bacterial virulence. Since prgB orthologs exist on a large number of conjugative plasmids in various different species, this makes PrgB a model protein for this widespread virulence factor. After characterizing the polymer adhesin domain of PrgB previously, we here report the structure for almost the entire remainder of PrgB, which reveals that PrgB contains four immunoglobulin (Ig)-like domains. Based on this new insight, we re-evaluate previously studied variants and present new in vivo data where specific domains or conserved residues have been removed. For the first time, we can show a decoupling of cellular aggregation from biofilm formation and conjugation in prgB mutant phenotypes. Based on the presented data, we propose a new functional model to explain how PrgB mediates its different functions. We hypothesize that the Ig-like domains act as a rigid stalk that presents the polymer adhesin domain at the right distance from the cell wall.

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  • 45. Szuba, Agata
    et al.
    Bano, Fouzia
    School of Biomedical Sciences, Faculty of Biological Sciences, Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, United Kingdom; School of Physics and Astronomy, Faculty of Engineering and Physical Sciences, University of Leeds, Leeds, United Kingdom; Bragg Centre for Materials Research, University of Leeds, Leeds, United Kingdom.
    Linares, Gerard Castro
    Iv, Francois
    Mavrakis, Manos
    Richter, Ralf P.
    Bertin, Aurélie
    Koenderink, Gijsje H.
    Membrane binding controls ordered self-assembly of animal septins2021Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 10, artikel-id e63349Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Septins are conserved cytoskeletal proteins that regulate cell cortex mechanics. The mechanisms of their interactions with the plasma membrane remain poorly understood. Here, we show by cell-free reconstitution that binding to flat lipid membranes requires electrostatic interactions of septins with anionic lipids and promotes the ordered self-assembly of fly septins into filamentous meshworks. Transmission electron microscopy reveals that both fly and mammalian septin hexamers form arrays of single and paired filaments. Atomic force microscopy and quartz crystal microbalance demonstrate that the fly filaments form mechanically rigid, 12- to 18-nm thick, double layers of septins. By contrast, C-terminally truncated septin mutants form 4-nm thin monolayers, indicating that stacking requires the C-terminal coiled coils on DSep2 and Pnut subunits. Our work shows that membrane binding is required for fly septins to form ordered arrays of single and paired filaments and provides new insights into the mechanisms by which septins may regulate cell surface mechanics.

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  • 46.
    Vidal-Pineiro, Didac
    et al.
    Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway.
    Wang, Yunpeng
    Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway.
    Krogsrud, Stine K.
    Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway.
    Amlien, Inge K.
    Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway.
    Baaré, William FC
    Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital-Amager and Hvidovre, Copenhagen, Denmark.
    Bartres-Faz, David
    Department of Medicine, Faculty of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
    Bertram, Lars
    Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway; Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), University of Lübeck, Lubeck, Germany.
    Brandmaier, Andreas M.
    Max Planck UCL Centre for Computational Psychiatry and Ageing Research, Berlin, Germany; Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany.
    Drevon, Christian A.
    Department of Nutrition, Inst Basic Med Sciences, Faculty of Medicine, University of Oslo & Vitas Ltd, Oslo, Norway.
    Düzel, Sandra
    Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany.
    Ebmeier, Klaus
    Department of Psychiatry, University of Oxford, Oxford, United Kingdom.
    Henson, Richard N.
    MRC Cognition and Brain Sciences Unit and Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
    Junqué, Carme
    Department of Medicine, Faculty of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
    Kievit, Rogier Andrew
    MRC Cognition and Brain Sciences Unit and Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom; Cognitive Neuroscience Department, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, Netherlands.
    Kühn, Simone
    Lise Meitner Group for Environmental Neuroscience, Max Planck Institute for Human Development, Berlin, Germany; Department of Psychiatry, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
    Leonardsen, Esten
    Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway.
    Lindenberger, Ulman
    Max Planck UCL Centre for Computational Psychiatry and Ageing Research, Berlin, Germany; Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany.
    Madsen, Kathrine S.
    Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital-Amager and Hvidovre, Copenhagen, Denmark; Radiography, Department of Technology, University College Copenhagen, Copenhagen, Denmark.
    Magnussen, Fredrik
    Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway.
    Mowinckel, Athanasia Monika
    Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Roe, James M.
    Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway.
    Segura, Barbara
    Department of Medicine, Faculty of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
    Smith, Stephen M.
    Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany.
    Sørensen, Øystein
    Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway.
    Suri, Sana
    Wellcome Centre for Integrative Neuroimaging (WIN FMRIB), University of Oxford, Oxford, United Kingdom; Wellcome Centre for Integrative Neuroimaging, Departments of Psychiatry and Clinical Neuroscience, University of Oxford, Oxford, United Kingdom.
    Westerhausen, Rene
    Section for Cognitive Neuroscience and Neuropsychology, Department of Psychology, University of Oslo, Oslo, Norway.
    Zalesky, Andrew
    Department of Biomedical Engineering, Faculty of Engineering and IT, The University of Melbourne, Melbourne, Australia.
    Zsoldos, Enikő
    Wellcome Centre for Integrative Neuroimaging, Departments of Psychiatry and Clinical Neuroscience, University of Oxford, Oxford, United Kingdom.
    Walhovd, Kristine Beate
    Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway; Department of radiology and nuclear medicine, Oslo University Hospital, Oslo, Norway.
    Fjell, Anders
    Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway; Department of radiology and nuclear medicine, Oslo University Hospital, Oslo, Norway.
    Individual variations in 'brain age' relate to early-life factors more than to longitudinal brain change2021Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 10, artikel-id e69995Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Brain age is a widely used index for quantifying individuals’ brain health as deviation from a normative brain aging trajectory. Higher-than-expected brain age is thought partially to reflect above-average rate of brain aging. Here, we explicitly tested this assumption in two indepen-dent large test datasets (UK Biobank [main] and Lifebrain [replication]; longitudinal observations ≈ 2750 and 4200) by assessing the relationship between cross-sectional and longitudinal estimates of brain age. Brain age models were estimated in two different training datasets (n ≈ 38,000 [main] and 1800 individuals [replication]) based on brain structural features. The results showed no association between cross-sectional brain age and the rate of brain change measured longitudinally. Rather, brain age in adulthood was associated with the congenital factors of birth weight and polygenic scores of brain age, assumed to reflect a constant, lifelong influence on brain structure from early life. The results call for nuanced interpretations of cross-sectional indices of the aging brain and question their validity as markers of ongoing within-person changes of the aging brain. Longitudinal imaging data should be preferred whenever the goal is to understand individual change trajectories of brain and cognition in aging.

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  • 47. Vigouroux, Antoine
    et al.
    Cordier, Baptiste
    Aristov, Andrey
    Alvarez, Laura
    Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Özbaykal, Gizem
    Chaze, Thibault
    Oldewurtel, Enno Rainer
    Matondo, Mariette
    Cava, Felipe
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Bikard, David
    van Teeffelen, Sven
    Class-A penicillin binding proteins do not contribute to cell shape but repair cell-wall defects2020Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 9, artikel-id e51998Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cell shape and cell-envelope integrity of bacteria are determined by the peptidoglycan cell wall. In rod-shaped Escherichia coli, two conserved sets of machinery are essential for cell-wall insertion in the cylindrical part of the cell: the Rod complex and the class-A penicillin-binding proteins (aPBPs). While the Rod complex governs rod-like cell shape, aPBP function is less well understood. aPBPs were previously hypothesized to either work in concert with the Rod complex or to independently repair cell-wall defects. First, we demonstrate through modulation of enzyme levels that aPBPs do not contribute to rod-like cell shape but are required for mechanical stability, supporting their independent activity. By combining measurements of cell-wall stiffness, cell-wall insertion, and PBP1b motion at the single-molecule level, we then present evidence that PBP1b, the major aPBP, contributes to cell-wall integrity by repairing cell wall defects.

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  • 48.
    Walker, Tom W. N.
    et al.
    Institute of Integrative Biology, ETH Zürich, Zürich, Switzerland.
    Gavazov, Konstantin
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och geovetenskap. Umeå universitet, Arktiskt centrum vid Umeå universitet (Arcum). Swiss Federal Institute for Forest, Snow and Landscape Research (WSL), Lausanne, Switzerland; École Polytechnique Fédérale de Lausanne EPFL, School of Architecture, Civil and Environmental Engineering ENAC, Laboratory of Ecological Systems ECOS and Plant Ecology Research Laboratory PERL, Lausanne, Switzerland.
    Guillaume, Thomas
    Swiss Federal Institute for Forest, Snow and Landscape Research (WSL), Lausanne, Switzerland; École Polytechnique Fédérale de Lausanne EPFL, School of Architecture, Civil and Environmental Engineering ENAC, Laboratory of Ecological Systems ECOS and Plant Ecology Research Laboratory PERL, Lausanne, Switzerland; Field-Crop Systems & Plant Nutrition, Agroscrope, Nyon, Switzerland.
    Lambert, Thibault
    Faculty of Geosciences & the Environment, Université de Lausanne, Lausanne, Switzerland.
    Mariotte, Pierre
    Swiss Federal Institute for Forest, Snow and Landscape Research (WSL), Lausanne, Switzerland; École Polytechnique Fédérale de Lausanne EPFL, School of Architecture, Civil and Environmental Engineering ENAC, Laboratory of Ecological Systems ECOS and Plant Ecology Research Laboratory PERL, Lausanne, Switzerland; Grazing Systems, Agroscrope, Posieux, Switzerland.
    Routh, Devin
    Institute of Integrative Biology, ETH Zürich, Zürich, Switzerland.
    Signarbieux, Constant
    Swiss Federal Institute for Forest, Snow and Landscape Research (WSL), Lausanne, Switzerland; École Polytechnique Fédérale de Lausanne EPFL, School of Architecture, Civil and Environmental Engineering ENAC, Laboratory of Ecological Systems ECOS and Plant Ecology Research Laboratory PERL, Lausanne, Switzerland.
    Block, Sebastián
    Institute of Integrative Biology, ETH Zürich, Zürich, Switzerland; Department of Ecology & Evolutionary Biology, Princeton University, Princeton, United States.
    Münkemüller, Tamara
    Uni. Grenoble Alpes, CNRS, Uni. Savoie Mont Blanc, LECA, Laboratoire d’Ecologie Alpine, Grenoble, France.
    Nomoto, Hanna
    Institute of Integrative Biology, ETH Zürich, Zürich, Switzerland.
    Crowther, Thomas W.
    Institute of Integrative Biology, ETH Zürich, Zürich, Switzerland.
    Richter, Andreas
    Centre of Microbiology & Environmental Systems, Division of Terrestrial Ecosystem Research, University of Vienna, Vienna, Austria.
    Buttler, Alexandre
    Swiss Federal Institute for Forest, Snow and Landscape Research (WSL), Lausanne, Switzerland; École Polytechnique Fédérale de Lausanne EPFL, School of Architecture, Civil and Environmental Engineering ENAC, Laboratory of Ecological Systems ECOS and Plant Ecology Research Laboratory PERL, Lausanne, Switzerland.
    Alexander, Jake M.
    Institute of Integrative Biology, ETH Zürich, Zürich, Switzerland; International Institute for Applied Systems Analysis, Ecosystem Services and Management Program, Laxenburg, Austria.
    Lowland plant arrival in alpine ecosystems facilitates a decrease in soil carbon content under experimental climate warming2022Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 11, artikel-id e78555Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Climate warming is releasing carbon from soils around the world1–3, constituting a positive climate feedback. Warming is also causing species to expand their ranges into new ecosystems4–9. Yet, in most ecosystems, whether range expanding species will amplify or buffer expected soil carbon loss is unknown10. Here we used two whole-community transplant experiments and a follow-up glasshouse experiment to determine whether the establishment of herbaceous lowland plants in alpine ecosystems influences soil carbon content under warming. We found that warming (transplantation to low elevation) led to a negligible decrease in alpine soil carbon content, but its effects became significant and 52% ± 31% (mean ± 95% CIs) larger after lowland plants were introduced at low density into the ecosystem. We present evidence that decreases in soil carbon content likely occurred via lowland plants increasing rates of root exudation, soil microbial respiration and CO2 release under warming. Our findings suggest that warming-induced range expansions of herbaceous plants have the potential to alter climate feedbacks from this system, and that plant range expansions among herbaceous communities may be an overlooked mediator of warming effects on carbon dynamics.

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  • 49.
    Weaver, Anna
    et al.
    Weill Institute for Cell and Molecular Biology, Cornell University, NY, Ithaca, United States; Department of Microbiology, Cornell University, NY, Ithaca, United States.
    Alvarez, Laura
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Rosch, Kelly
    Weill Institute for Cell and Molecular Biology, Cornell University, NY, Ithaca, United States.
    Ahmed, Asraa
    Weill Institute for Cell and Molecular Biology, Cornell University, NY, Ithaca, United States; Cornell Institute of Host-Microbe Interactions and Disease, Cornell University, NY, Ithaca, United States.
    Wang, Garrett
    Weill Institute for Cell and Molecular Biology, Cornell University, NY, Ithaca, United States.
    Van Nieuwenhze, Michael
    Department of Molecular and Cellular Biochemistry, Indiana University, IN, Bloomington, United States; Department of Chemistry, Indiana University, IN, Bloomington, United States.
    Cava, Felipe
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Dörr, Tobias
    Weill Institute for Cell and Molecular Biology, Cornell University, NY, Ithaca, United States; Department of Microbiology, Cornell University, NY, Ithaca, United States; Cornell Institute of Host-Microbe Interactions and Disease, Cornell University, NY, Ithaca, United States.
    Lytic transglycosylases mitigate periplasmic crowding by degrading soluble cell wall turnover products2022Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 11, artikel-id e73178Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The peptidoglycan cell wall is a predominant structure of bacteria, determining cell shape and supporting survival in diverse conditions. Peptidoglycan is dynamic and requires regulated synthesis of new material, remodeling, and turnover – or autolysis – of old material. Despite exploitation of peptidoglycan synthesis as an antibiotic target, we lack a fundamental understanding of how peptidoglycan synthesis and autolysis intersect to maintain the cell wall. Here, we uncover a critical physiological role for a widely misunderstood class of autolytic enzymes, lytic transglycosylases (LTGs). We demonstrate that LTG activity is essential to survival by contributing to periplasmic processes upstream and independent of peptidoglycan recycling. Defects accumulate in Vibrio cholerae LTG mutants due to generally inadequate LTG activity, rather than absence of specific enzymes, and essential LTG activities are likely independent of protein-protein interactions, as heterologous expression of a non-native LTG rescues growth of a conditionally LTG-null mutant. Lastly, we demonstrate that soluble, uncrosslinked, endopeptidase-dependent peptidoglycan chains, also detected in the wild-type, are enriched in LTG mutants, and that LTG mutants are hypersusceptible to the production of diverse periplasmic polymers. Collectively, our results suggest that LTGs prevent toxic crowding of the periplasm with synthesis-derived peptidoglycan polymers and contrary to prevailing models, that this autolytic function can be temporally separate from peptidoglycan synthesis.

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  • 50. 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 proteins2017Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 6, artikel-id e23905Artikel i tidskrift (Refereegranskat)
    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.

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