TY  - JOUR
A1  - Wuttke, Matthias
A1  - Li, Yong
A1  - Li, Man
A1  - Sieber, Karsten B.
A1  - Feitosa, Mary F.
A1  - Gorski, Mathias
A1  - Tin, Adrienne
A1  - Wang, Lihua
A1  - Chu, Audrey Y.
A1  - Hoppmann, Anselm
A1  - Kirsten, Holger
A1  - Giri, Ayush
A1  - Chai, Jin-Fang
A1  - Sveinbjornsson, Gardar
A1  - Tayo, Bamidele O.
A1  - Nutile, Teresa
A1  - Fuchsberger, Christian
A1  - Marten, Jonathan
A1  - Cocca, Massimiliano
A1  - Ghasemi, Sahar
A1  - Xu, Yizhe
A1  - Horn, Katrin
A1  - Noce, Damia
A1  - Van der Most, Peter J.
A1  - Sedaghat, Sanaz
A1  - Yu, Zhi
A1  - Akiyama, Masato
A1  - Afaq, Saima
A1  - Ahluwalia, Tarunveer Singh
A1  - Almgren, Peter
A1  - Amin, Najaf
A1  - Arnlov, Johan
A1  - Bakker, Stephan J. L.
A1  - Bansal, Nisha
A1  - Baptista, Daniela
A1  - Bergmann, Sven
A1  - Biggs, Mary L.
A1  - Biino, Ginevra
A1  - Boehnke, Michael
A1  - Boerwinkle, Eric
A1  - Boissel, Mathilde
A1  - Böttinger, Erwin
A1  - Boutin, Thibaud S.
A1  - Brenner, Hermann
A1  - Brumat, Marco
A1  - Burkhardt, Ralph
A1  - Butterworth, Adam S.
A1  - Campana, Eric
A1  - Campbell, Archie
A1  - Campbell, Harry
A1  - Canouil, Mickael
A1  - Carroll, Robert J.
A1  - Catamo, Eulalia
A1  - Chambers, John C.
A1  - Chee, Miao-Ling
A1  - Chee, Miao-Li
A1  - Chen, Xu
A1  - Cheng, Ching-Yu
A1  - Cheng, Yurong
A1  - Christensen, Kaare
A1  - Cifkova, Renata
A1  - Ciullo, Marina
A1  - Concas, Maria Pina
A1  - Cook, James P.
A1  - Coresh, Josef
A1  - Corre, Tanguy
A1  - Sala, Cinzia Felicita
A1  - Cusi, Daniele
A1  - Danesh, John
A1  - Daw, E. Warwick
A1  - De Borst, Martin H.
A1  - De Grandi, Alessandro
A1  - De Mutsert, Renee
A1  - De Vries, Aiko P. J.
A1  - Degenhardt, Frauke
A1  - Delgado, Graciela
A1  - Demirkan, Ayse
A1  - Di Angelantonio, Emanuele
A1  - Dittrich, Katalin
A1  - Divers, Jasmin
A1  - Dorajoo, Rajkumar
A1  - Eckardt, Kai-Uwe
A1  - Ehret, Georg
A1  - Elliott, Paul
A1  - Endlich, Karlhans
A1  - Evans, Michele K.
A1  - Felix, Janine F.
A1  - Foo, Valencia Hui Xian
A1  - Franco, Oscar H.
A1  - Franke, Andre
A1  - Freedman, Barry I.
A1  - Freitag-Wolf, Sandra
A1  - Friedlander, Yechiel
A1  - Froguel, Philippe
A1  - Gansevoort, Ron T.
A1  - Gao, He
A1  - Gasparini, Paolo
A1  - Gaziano, J. Michael
A1  - Giedraitis, Vilmantas
A1  - Gieger, Christian
A1  - Girotto, Giorgia
A1  - Giulianini, Franco
A1  - Gogele, Martin
A1  - Gordon, Scott D.
A1  - Gudbjartsson, Daniel F.
A1  - Gudnason, Vilmundur
A1  - Haller, Toomas
A1  - Hamet, Pavel
A1  - Harris, Tamara B.
A1  - Hartman, Catharina A.
A1  - Hayward, Caroline
A1  - Hellwege, Jacklyn N.
A1  - Heng, Chew-Kiat
A1  - Hicks, Andrew A.
A1  - Hofer, Edith
A1  - Huang, Wei
A1  - Hutri-Kahonen, Nina
A1  - Hwang, Shih-Jen
A1  - Ikram, M. Arfan
A1  - Indridason, Olafur S.
A1  - Ingelsson, Erik
A1  - Ising, Marcus
A1  - Jaddoe, Vincent W. V.
A1  - Jakobsdottir, Johanna
A1  - Jonas, Jost B.
A1  - Joshi, Peter K.
A1  - Josyula, Navya Shilpa
A1  - Jung, Bettina
A1  - Kahonen, Mika
A1  - Kamatani, Yoichiro
A1  - Kammerer, Candace M.
A1  - Kanai, Masahiro
A1  - Kastarinen, Mika
A1  - Kerr, Shona M.
A1  - Khor, Chiea-Chuen
A1  - Kiess, Wieland
A1  - Kleber, Marcus E.
A1  - Koenig, Wolfgang
A1  - Kooner, Jaspal S.
A1  - Korner, Antje
A1  - Kovacs, Peter
A1  - Kraja, Aldi T.
A1  - Krajcoviechova, Alena
A1  - Kramer, Holly
A1  - Kramer, Bernhard K.
A1  - Kronenberg, Florian
A1  - Kubo, Michiaki
A1  - Kuhnel, Brigitte
A1  - Kuokkanen, Mikko
A1  - Kuusisto, Johanna
A1  - La Bianca, Martina
A1  - Laakso, Markku
A1  - Lange, Leslie A.
A1  - Langefeld, Carl D.
A1  - Lee, Jeannette Jen-Mai
A1  - Lehne, Benjamin
A1  - Lehtimaki, Terho
A1  - Lieb, Wolfgang
A1  - Lim, Su-Chi
A1  - Lind, Lars
A1  - Lindgren, Cecilia M.
A1  - Liu, Jun
A1  - Liu, Jianjun
A1  - Loeffler, Markus
A1  - Loos, Ruth J. F.
A1  - Lucae, Susanne
A1  - Lukas, Mary Ann
A1  - Lyytikainen, Leo-Pekka
A1  - Magi, Reedik
A1  - Magnusson, Patrik K. E.
A1  - Mahajan, Anubha
A1  - Martin, Nicholas G.
A1  - Martins, Jade
A1  - Marz, Winfried
A1  - Mascalzoni, Deborah
A1  - Matsuda, Koichi
A1  - Meisinger, Christa
A1  - Meitinger, Thomas
A1  - Melander, Olle
A1  - Metspalu, Andres
A1  - Mikaelsdottir, Evgenia K.
A1  - Milaneschi, Yuri
A1  - Miliku, Kozeta
A1  - Mishra, Pashupati P.
A1  - Program, V. A. Million Veteran
A1  - Mohlke, Karen L.
A1  - Mononen, Nina
A1  - Montgomery, Grant W.
A1  - Mook-Kanamori, Dennis O.
A1  - Mychaleckyj, Josyf C.
A1  - Nadkarni, Girish N.
A1  - Nalls, Mike A.
A1  - Nauck, Matthias
A1  - Nikus, Kjell
A1  - Ning, Boting
A1  - Nolte, Ilja M.
A1  - Noordam, Raymond
A1  - Olafsson, Isleifur
A1  - Oldehinkel, Albertine J.
A1  - Orho-Melander, Marju
A1  - Ouwehand, Willem H.
A1  - Padmanabhan, Sandosh
A1  - Palmer, Nicholette D.
A1  - Palsson, Runolfur
A1  - Penninx, Brenda W. J. H.
A1  - Perls, Thomas
A1  - Perola, Markus
A1  - Pirastu, Mario
A1  - Pirastu, Nicola
A1  - Pistis, Giorgio
A1  - Podgornaia, Anna I.
A1  - Polasek, Ozren
A1  - Ponte, Belen
A1  - Porteous, David J.
A1  - Poulain, Tanja
A1  - Pramstaller, Peter P.
A1  - Preuss, Michael H.
A1  - Prins, Bram P.
A1  - Province, Michael A.
A1  - Rabelink, Ton J.
A1  - Raffield, Laura M.
A1  - Raitakari, Olli T.
A1  - Reilly, Dermot F.
A1  - Rettig, Rainer
A1  - Rheinberger, Myriam
A1  - Rice, Kenneth M.
A1  - Ridker, Paul M.
A1  - Rivadeneira, Fernando
A1  - Rizzi, Federica
A1  - Roberts, David J.
A1  - Robino, Antonietta
A1  - Rossing, Peter
A1  - Rudan, Igor
A1  - Rueedi, Rico
A1  - Ruggiero, Daniela
A1  - Ryan, Kathleen A.
A1  - Saba, Yasaman
A1  - Sabanayagam, Charumathi
A1  - Salomaa, Veikko
A1  - Salvi, Erika
A1  - Saum, Kai-Uwe
A1  - Schmidt, Helena
A1  - Schmidt, Reinhold
A1  - Ben Schottker, 
A1  - Schulz, Christina-Alexandra
A1  - Schupf, Nicole
A1  - Shaffer, Christian M.
A1  - Shi, Yuan
A1  - Smith, Albert V.
A1  - Smith, Blair H.
A1  - Soranzo, Nicole
A1  - Spracklen, Cassandra N.
A1  - Strauch, Konstantin
A1  - Stringham, Heather M.
A1  - Stumvoll, Michael
A1  - Svensson, Per O.
A1  - Szymczak, Silke
A1  - Tai, E-Shyong
A1  - Tajuddin, Salman M.
A1  - Tan, Nicholas Y. Q.
A1  - Taylor, Kent D.
A1  - Teren, Andrej
A1  - Tham, Yih-Chung
A1  - Thiery, Joachim
A1  - Thio, Chris H. L.
A1  - Thomsen, Hauke
A1  - Thorleifsson, Gudmar
A1  - Toniolo, Daniela
A1  - Tonjes, Anke
A1  - Tremblay, Johanne
A1  - Tzoulaki, Ioanna
A1  - Uitterlinden, Andre G.
A1  - Vaccargiu, Simona
A1  - Van Dam, Rob M.
A1  - Van der Harst, Pim
A1  - Van Duijn, Cornelia M.
A1  - Edward, Digna R. Velez
A1  - Verweij, Niek
A1  - Vogelezang, Suzanne
A1  - Volker, Uwe
A1  - Vollenweider, Peter
A1  - Waeber, Gerard
A1  - Waldenberger, Melanie
A1  - Wallentin, Lars
A1  - Wang, Ya Xing
A1  - Wang, Chaolong
A1  - Waterworth, Dawn M.
A1  - Bin Wei, Wen
A1  - White, Harvey
A1  - Whitfield, John B.
A1  - Wild, Sarah H.
A1  - Wilson, James F.
A1  - Wojczynski, Mary K.
A1  - Wong, Charlene
A1  - Wong, Tien-Yin
A1  - Xu, Liang
A1  - Yang, Qiong
A1  - Yasuda, Masayuki
A1  - Yerges-Armstrong, Laura M.
A1  - Zhang, Weihua
A1  - Zonderman, Alan B.
A1  - Rotter, Jerome I.
A1  - Bochud, Murielle
A1  - Psaty, Bruce M.
A1  - Vitart, Veronique
A1  - Wilson, James G.
A1  - Dehghan, Abbas
A1  - Parsa, Afshin
A1  - Chasman, Daniel I.
A1  - Ho, Kevin
A1  - Morris, Andrew P.
A1  - Devuyst, Olivier
A1  - Akilesh, Shreeram
A1  - Pendergrass, Sarah A.
A1  - Sim, Xueling
A1  - Boger, Carsten A.
A1  - Okada, Yukinori
A1  - Edwards, Todd L.
A1  - Snieder, Harold
A1  - Stefansson, Kari
A1  - Hung, Adriana M.
A1  - Heid, Iris M.
A1  - Scholz, Markus
A1  - Teumer, Alexander
A1  - Kottgen, Anna
A1  - Pattaro, Cristian
T1  - A catalog of genetic loci associated with kidney function from analyses of a million individuals
JF  - Nature genetics
N2  - Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
Y1  - 2019
U6  - https://doi.org/10.1038/s41588-019-0407-x
SN  - 1061-4036
SN  - 1546-1718
VL  - 51
IS  - 6
SP  - 957
EP  - +
PB  - Nature Publ. Group
CY  - New York
ER  - 
TY  - GEN
A1  - Gorski, Mathias
A1  - Jung, Bettina
A1  - Li, Yong
A1  - Matias-Garcia, Pamela R.
A1  - Wuttke, Matthias
A1  - Coassin, Stefan
A1  - Thio, Chris H. L.
A1  - Kleber, Marcus E.
A1  - Winkler, Thomas W.
A1  - Wanner, Veronika
A1  - Chai, Jin-Fang
A1  - Chu, Audrey Y.
A1  - Cocca, Massimiliano
A1  - Feitosa, Mary F.
A1  - Ghasemi, Sahar
A1  - Hoppmann, Anselm
A1  - Horn, Katrin
A1  - Li, Man
A1  - Nutile, Teresa
A1  - Scholz, Markus
A1  - Sieber, Karsten B.
A1  - Teumer, Alexander
A1  - Tin, Adrienne
A1  - Wang, Judy
A1  - Tayo, Bamidele O.
A1  - Ahluwalia, Tarunveer S.
A1  - Almgren, Peter
A1  - Bakker, Stephan J. L.
A1  - Banas, Bernhard
A1  - Bansal, Nisha
A1  - Biggs, Mary L.
A1  - Boerwinkle, Eric
A1  - Böttinger, Erwin
A1  - Brenner, Hermann
A1  - Carroll, Robert J.
A1  - Chalmers, John
A1  - Chee, Miao-Li
A1  - Chee, Miao-Ling
A1  - Cheng, Ching-Yu
A1  - Coresh, Josef
A1  - de Borst, Martin H.
A1  - Degenhardt, Frauke
A1  - Eckardt, Kai-Uwe
A1  - Endlich, Karlhans
A1  - Franke, Andre
A1  - Freitag-Wolf, Sandra
A1  - Gampawar, Piyush
A1  - Gansevoort, Ron T.
A1  - Ghanbari, Mohsen
A1  - Gieger, Christian
A1  - Hamet, Pavel
A1  - Ho, Kevin
A1  - Hofer, Edith
A1  - Holleczek, Bernd
A1  - Foo, Valencia Hui Xian
A1  - Hutri-Kahonen, Nina
A1  - Hwang, Shih-Jen
A1  - Ikram, M. Arfan
A1  - Josyula, Navya Shilpa
A1  - Kahonen, Mika
A1  - Khor, Chiea-Chuen
A1  - Koenig, Wolfgang
A1  - Kramer, Holly
A1  - Kraemer, Bernhard K.
A1  - Kuehnel, Brigitte
A1  - Lange, Leslie A.
A1  - Lehtimaki, Terho
A1  - Lieb, Wolfgang
A1  - Loos, Ruth J. F.
A1  - Lukas, Mary Ann
A1  - Lyytikainen, Leo-Pekka
A1  - Meisinger, Christa
A1  - Meitinger, Thomas
A1  - Melander, Olle
A1  - Milaneschi, Yuri
A1  - Mishra, Pashupati P.
A1  - Mononen, Nina
A1  - Mychaleckyj, Josyf C.
A1  - Nadkarni, Girish N.
A1  - Nauck, Matthias
A1  - Nikus, Kjell
A1  - Ning, Boting
A1  - Nolte, Ilja M.
A1  - O'Donoghue, Michelle L.
A1  - Orho-Melander, Marju
A1  - Pendergrass, Sarah A.
A1  - Penninx, Brenda W. J. H.
A1  - Preuss, Michael H.
A1  - Psaty, Bruce M.
A1  - Raffield, Laura M.
A1  - Raitakari, Olli T.
A1  - Rettig, Rainer
A1  - Rheinberger, Myriam
A1  - Rice, Kenneth M.
A1  - Rosenkranz, Alexander R.
A1  - Rossing, Peter
A1  - Rotter, Jerome
A1  - Sabanayagam, Charumathi
A1  - Schmidt, Helena
A1  - Schmidt, Reinhold
A1  - Schoettker, Ben
A1  - Schulz, Christina-Alexandra
A1  - Sedaghat, Sanaz
A1  - Shaffer, Christian M.
A1  - Strauch, Konstantin
A1  - Szymczak, Silke
A1  - Taylor, Kent D.
A1  - Tremblay, Johanne
A1  - Chaker, Layal
A1  - van der Harst, Pim
A1  - van der Most, Peter J.
A1  - Verweij, Niek
A1  - Voelker, Uwe
A1  - Waldenberger, Melanie
A1  - Wallentin, Lars
A1  - Waterworth, Dawn M.
A1  - White, Harvey D.
A1  - Wilson, James G.
A1  - Wong, Tien-Yin
A1  - Woodward, Mark
A1  - Yang, Qiong
A1  - Yasuda, Masayuki
A1  - Yerges-Armstrong, Laura M.
A1  - Zhang, Yan
A1  - Snieder, Harold
A1  - Wanner, Christoph
A1  - Boger, Carsten A.
A1  - Kottgen, Anna
A1  - Kronenberg, Florian
A1  - Pattaro, Cristian
A1  - Heid, Iris M.
T1  - Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline
T2  - Zweitveröffentlichungen der Universität Potsdam : Reihe der Digital Engineering Fakultät
N2  - Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
T3  - Zweitveröffentlichungen der Universität Potsdam : Reihe der Digital Engineering Fakultät - 19 
KW  - acute kidney injury
KW  - end-stage kidney disease
KW  - genome-wide association
KW  - study
KW  - rapid eGFRcrea decline
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-565379
IS  - 19
ER  - 
TY  - JOUR
A1  - Gorski, Mathias
A1  - Jung, Bettina
A1  - Li, Yong
A1  - Matias-Garcia, Pamela R.
A1  - Wuttke, Matthias
A1  - Coassin, Stefan
A1  - Thio, Chris H. L.
A1  - Kleber, Marcus E.
A1  - Winkler, Thomas W.
A1  - Wanner, Veronika
A1  - Chai, Jin-Fang
A1  - Chu, Audrey Y.
A1  - Cocca, Massimiliano
A1  - Feitosa, Mary F.
A1  - Ghasemi, Sahar
A1  - Hoppmann, Anselm
A1  - Horn, Katrin
A1  - Li, Man
A1  - Nutile, Teresa
A1  - Scholz, Markus
A1  - Sieber, Karsten B.
A1  - Teumer, Alexander
A1  - Tin, Adrienne
A1  - Wang, Judy
A1  - Tayo, Bamidele O.
A1  - Ahluwalia, Tarunveer S.
A1  - Almgren, Peter
A1  - Bakker, Stephan J. L.
A1  - Banas, Bernhard
A1  - Bansal, Nisha
A1  - Biggs, Mary L.
A1  - Boerwinkle, Eric
A1  - Böttinger, Erwin
A1  - Brenner, Hermann
A1  - Carroll, Robert J.
A1  - Chalmers, John
A1  - Chee, Miao-Li
A1  - Chee, Miao-Ling
A1  - Cheng, Ching-Yu
A1  - Coresh, Josef
A1  - de Borst, Martin H.
A1  - Degenhardt, Frauke
A1  - Eckardt, Kai-Uwe
A1  - Endlich, Karlhans
A1  - Franke, Andre
A1  - Freitag-Wolf, Sandra
A1  - Gampawar, Piyush
A1  - Gansevoort, Ron T.
A1  - Ghanbari, Mohsen
A1  - Gieger, Christian
A1  - Hamet, Pavel
A1  - Ho, Kevin
A1  - Hofer, Edith
A1  - Holleczek, Bernd
A1  - Foo, Valencia Hui Xian
A1  - Hutri-Kahonen, Nina
A1  - Hwang, Shih-Jen
A1  - Ikram, M. Arfan
A1  - Josyula, Navya Shilpa
A1  - Kahonen, Mika
A1  - Khor, Chiea-Chuen
A1  - Koenig, Wolfgang
A1  - Kramer, Holly
A1  - Kraemer, Bernhard K.
A1  - Kuehnel, Brigitte
A1  - Lange, Leslie A.
A1  - Lehtimaki, Terho
A1  - Lieb, Wolfgang
A1  - Loos, Ruth J. F.
A1  - Lukas, Mary Ann
A1  - Lyytikainen, Leo-Pekka
A1  - Meisinger, Christa
A1  - Meitinger, Thomas
A1  - Melander, Olle
A1  - Milaneschi, Yuri
A1  - Mishra, Pashupati P.
A1  - Mononen, Nina
A1  - Mychaleckyj, Josyf C.
A1  - Nadkarni, Girish N.
A1  - Nauck, Matthias
A1  - Nikus, Kjell
A1  - Ning, Boting
A1  - Nolte, Ilja M.
A1  - O'Donoghue, Michelle L.
A1  - Orho-Melander, Marju
A1  - Pendergrass, Sarah A.
A1  - Penninx, Brenda W. J. H.
A1  - Preuss, Michael H.
A1  - Psaty, Bruce M.
A1  - Raffield, Laura M.
A1  - Raitakari, Olli T.
A1  - Rettig, Rainer
A1  - Rheinberger, Myriam
A1  - Rice, Kenneth M.
A1  - Rosenkranz, Alexander R.
A1  - Rossing, Peter
A1  - Rotter, Jerome
A1  - Sabanayagam, Charumathi
A1  - Schmidt, Helena
A1  - Schmidt, Reinhold
A1  - Schoettker, Ben
A1  - Schulz, Christina-Alexandra
A1  - Sedaghat, Sanaz
A1  - Shaffer, Christian M.
A1  - Strauch, Konstantin
A1  - Szymczak, Silke
A1  - Taylor, Kent D.
A1  - Tremblay, Johanne
A1  - Chaker, Layal
A1  - van der Harst, Pim
A1  - van der Most, Peter J.
A1  - Verweij, Niek
A1  - Voelker, Uwe
A1  - Waldenberger, Melanie
A1  - Wallentin, Lars
A1  - Waterworth, Dawn M.
A1  - White, Harvey D.
A1  - Wilson, James G.
A1  - Wong, Tien-Yin
A1  - Woodward, Mark
A1  - Yang, Qiong
A1  - Yasuda, Masayuki
A1  - Yerges-Armstrong, Laura M.
A1  - Zhang, Yan
A1  - Snieder, Harold
A1  - Wanner, Christoph
A1  - Boger, Carsten A.
A1  - Kottgen, Anna
A1  - Kronenberg, Florian
A1  - Pattaro, Cristian
A1  - Heid, Iris M.
T1  - Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline
JF  - Kidney international : official journal of the International Society of Nephrology
N2  - Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
KW  - acute kidney injury
KW  - end-stage kidney disease
KW  - genome-wide association
KW  - study
KW  - rapid eGFRcrea decline
Y1  - 2020
U6  - https://doi.org/10.1016/j.kint.2020.09.030
SN  - 0085-2538
SN  - 1523-1755
VL  - 99
IS  - 4
SP  - 926
EP  - 939
PB  - Elsevier
CY  - New York
ER  - 
TY  - JOUR
A1  - Tang, Alan T.
A1  - Sullivan, Katie Rose
A1  - Hong, Courtney C.
A1  - Goddard, Lauren M.
A1  - Mahadevan, Aparna
A1  - Ren, Aileen
A1  - Pardo, Heidy
A1  - Peiper, Amy
A1  - Griffin, Erin
A1  - Tanes, Ceylan
A1  - Mattei, Lisa M.
A1  - Yang, Jisheng
A1  - Li, Li
A1  - Mericko-Ishizuka, Patricia
A1  - Shen, Le
A1  - Hobson, Nicholas
A1  - Girard, Romuald
A1  - Lightle, Rhonda
A1  - Moore, Thomas
A1  - Shenkar, Robert
A1  - Polster, Sean P.
A1  - Roedel, Claudia Jasmin
A1  - Li, Ning
A1  - Zhu, Qin
A1  - Whitehead, Kevin J.
A1  - Zheng, Xiangjian
A1  - Akers, Amy
A1  - Morrison, Leslie
A1  - Kim, Helen
A1  - Bittinger, Kyle
A1  - Lengner, Christopher J.
A1  - Schwaninger, Markus
A1  - Velcich, Anna
A1  - Augenlicht, Leonard
A1  - Abdelilah-Seyfried, Salim
A1  - Min, Wang
A1  - Marchuk, Douglas A.
A1  - Awad, Issam A.
A1  - Kahn, Mark L.
T1  - Distinct cellular roles for PDCD10 define a gut-brain axis in cerebral cavernous malformation
JF  - Science Translational Medicine
N2  - Cerebral cavernous malformation (CCM) is a genetic, cerebrovascular disease. Familial CCM is caused by genetic mutations in KRIT1, CCM2, or PDCD10. Disease onset is earlier and more severe in individuals with PDCD10 mutations. Recent studies have shown that lesions arise from excess mitogen-activated protein kinase kinase kinase 3 (MEKK3) signaling downstream of Toll-like receptor 4 (TLR4) stimulation by lipopolysaccharide derived from the gut microbiome. These findings suggest a gut-brain CCM disease axis but fail to define it or explain the poor prognosis of patients with PDCD10 mutations. Here, we demonstrate that the gut barrier is a primary determinant of CCM disease course, independent of microbiome configuration, that explains the increased severity of CCM disease associated with PDCD10 deficiency. Chemical disruption of the gut barrier with dextran sulfate sodium augments CCM formation in a mouse model, as does genetic loss of Pdcd10, but not Krit1, in gut epithelial cells. Loss of gut epithelial Pdcd10 results in disruption of the colonic mucosal barrier. Accordingly, loss of Mucin-2 or exposure to dietary emulsifiers that reduce the mucus barrier increases CCM burden analogous to loss of Pdcd10 in the gut epithelium. Last, we show that treatment with dexamethasone potently inhibits CCM formation in mice because of the combined effect of action at both brain endothelial cells and gut epithelial cells. These studies define a gut-brain disease axis in an experimental model of CCM in which a single gene is required for two critical components: gut epithelial function and brain endothelial signaling.
Y1  - 2019
U6  - https://doi.org/10.1126/scitranslmed.aaw3521
SN  - 1946-6234
SN  - 1946-6242
VL  - 11
IS  - 520
PB  - American Assoc. for the Advancement of Science
CY  - Washington
ER  - 
TY  - JOUR
A1  - Banks, Jo Ann
A1  - Nishiyama, Tomoaki
A1  - Hasebe, Mitsuyasu
A1  - Bowman, John L.
A1  - Gribskov, Michael
A1  - dePamphilis, Claude
A1  - Albert, Victor A.
A1  - Aono, Naoki
A1  - Aoyama, Tsuyoshi
A1  - Ambrose, Barbara A.
A1  - Ashton, Neil W.
A1  - Axtell, Michael J.
A1  - Barker, Elizabeth
A1  - Barker, Michael S.
A1  - Bennetzen, Jeffrey L.
A1  - Bonawitz, Nicholas D.
A1  - Chapple, Clint
A1  - Cheng, Chaoyang
A1  - Correa, Luiz Gustavo Guedes
A1  - Dacre, Michael
A1  - DeBarry, Jeremy
A1  - Dreyer, Ingo
A1  - Elias, Marek
A1  - Engstrom, Eric M.
A1  - Estelle, Mark
A1  - Feng, Liang
A1  - Finet, Cedric
A1  - Floyd, Sandra K.
A1  - Frommer, Wolf B.
A1  - Fujita, Tomomichi
A1  - Gramzow, Lydia
A1  - Gutensohn, Michael
A1  - Harholt, Jesper
A1  - Hattori, Mitsuru
A1  - Heyl, Alexander
A1  - Hirai, Tadayoshi
A1  - Hiwatashi, Yuji
A1  - Ishikawa, Masaki
A1  - Iwata, Mineko
A1  - Karol, Kenneth G.
A1  - Koehler, Barbara
A1  - Kolukisaoglu, Uener
A1  - Kubo, Minoru
A1  - Kurata, Tetsuya
A1  - Lalonde, Sylvie
A1  - Li, Kejie
A1  - Li, Ying
A1  - Litt, Amy
A1  - Lyons, Eric
A1  - Manning, Gerard
A1  - Maruyama, Takeshi
A1  - Michael, Todd P.
A1  - Mikami, Koji
A1  - Miyazaki, Saori
A1  - Morinaga, Shin-ichi
A1  - Murata, Takashi
A1  - Müller-Röber, Bernd
A1  - Nelson, David R.
A1  - Obara, Mari
A1  - Oguri, Yasuko
A1  - Olmstead, Richard G.
A1  - Onodera, Naoko
A1  - Petersen, Bent Larsen
A1  - Pils, Birgit
A1  - Prigge, Michael
A1  - Rensing, Stefan A.
A1  - Mauricio Riano-Pachon, Diego
A1  - Roberts, Alison W.
A1  - Sato, Yoshikatsu
A1  - Scheller, Henrik Vibe
A1  - Schulz, Burkhard
A1  - Schulz, Christian
A1  - Shakirov, Eugene V.
A1  - Shibagaki, Nakako
A1  - Shinohara, Naoki
A1  - Shippen, Dorothy E.
A1  - Sorensen, Iben
A1  - Sotooka, Ryo
A1  - Sugimoto, Nagisa
A1  - Sugita, Mamoru
A1  - Sumikawa, Naomi
A1  - Tanurdzic, Milos
A1  - Theissen, Guenter
A1  - Ulvskov, Peter
A1  - Wakazuki, Sachiko
A1  - Weng, Jing-Ke
A1  - Willats, William W. G. T.
A1  - Wipf, Daniel
A1  - Wolf, Paul G.
A1  - Yang, Lixing
A1  - Zimmer, Andreas D.
A1  - Zhu, Qihui
A1  - Mitros, Therese
A1  - Hellsten, Uffe
A1  - Loque, Dominique
A1  - Otillar, Robert
A1  - Salamov, Asaf
A1  - Schmutz, Jeremy
A1  - Shapiro, Harris
A1  - Lindquist, Erika
A1  - Lucas, Susan
A1  - Rokhsar, Daniel
A1  - Grigoriev, Igor V.
T1  - The selaginella genome identifies genetic changes associated with the evolution of vascular plants
JF  - Science
N2  - Vascular plants appeared similar to 410 million years ago, then diverged into several lineages of which only two survive: the euphyllophytes (ferns and seed plants) and the lycophytes. We report here the genome sequence of the lycophyte Selaginella moellendorffii (Selaginella), the first nonseed vascular plant genome reported. By comparing gene content in evolutionarily diverse taxa, we found that the transition from a gametophyte- to a sporophyte-dominated life cycle required far fewer new genes than the transition from a nonseed vascular to a flowering plant, whereas secondary metabolic genes expanded extensively and in parallel in the lycophyte and angiosperm lineages. Selaginella differs in posttranscriptional gene regulation, including small RNA regulation of repetitive elements, an absence of the trans-acting small interfering RNA pathway, and extensive RNA editing of organellar genes.
Y1  - 2011
U6  - https://doi.org/10.1126/science.1203810
SN  - 0036-8075
VL  - 332
IS  - 6032
SP  - 960
EP  - 963
PB  - American Assoc. for the Advancement of Science
CY  - Washington
ER  - 
TY  - JOUR
A1  - Abeysekara, A. U.
A1  - Archer, A.
A1  - Benbow, Wystan
A1  - Bird, Ralph
A1  - Brose, Robert
A1  - Buchovecky, M.
A1  - Buckley, J. H.
A1  - Bugaev, V.
A1  - Chromey, A. J.
A1  - Connolly, M. P.
A1  - Cui, Wei
A1  - Daniel, M. K.
A1  - Falcone, A.
A1  - Feng, Qi
A1  - Finley, John P.
A1  - Fortson, L.
A1  - Furniss, Amy
A1  - Huetten, M.
A1  - Hanna, David
A1  - Hervet, O.
A1  - Holder, J.
A1  - Hughes, G.
A1  - Humensky, T. B.
A1  - Johnson, Caitlin A.
A1  - Kaaret, Philip
A1  - Kar, P.
A1  - Kertzman, M.
A1  - Kieda, David
A1  - Krause, M.
A1  - Krennrich, F.
A1  - Kumar, S.
A1  - Lang, M. J.
A1  - Lin, T. T. Y.
A1  - McArthur, S.
A1  - Moriarty, P.
A1  - Mukherjee, Reshmi
A1  - Ong, R. A.
A1  - Otte, Adam Nepomuk
A1  - Park, Nahee
A1  - Petrashyk, A.
A1  - Pohl, Martin
A1  - Pueschel, Elisa
A1  - Quinn, J.
A1  - Ragan, K.
A1  - Reynolds, P. T.
A1  - Richards, Gregory T.
A1  - Roache, E.
A1  - Rulten, C.
A1  - Sadeh, I.
A1  - Santander, Marcos
A1  - Sembroski, G. H.
A1  - Shahinyan, Karlen
A1  - Sushch, I.
A1  - Tyler, J.
A1  - Wakely, S. P.
A1  - Weinstein, A.
A1  - Wells, R. M.
A1  - Wilcox, P.
A1  - Wilhelm, Alina
A1  - Williams, D. A.
A1  - Williamson, T. J.
A1  - Zitzer, B.
A1  - Abdollahi, S.
A1  - Ajello, Marco
A1  - Baldini, Luca
A1  - Barbiellini, G.
A1  - Bastieri, Denis
A1  - Bellazzini, Ronaldo
A1  - Berenji, B.
A1  - Bissaldi, Elisabetta
A1  - Blandford, R. D.
A1  - Bonino, R.
A1  - Bottacini, E.
A1  - Brandt, Terri J.
A1  - Bruel, P.
A1  - Buehler, R.
A1  - Cameron, R. A.
A1  - Caputo, R.
A1  - Caraveo, P. A.
A1  - Castro, D.
A1  - Cavazzuti, E.
A1  - Charles, Eric
A1  - Chiaro, G.
A1  - Ciprini, S.
A1  - Cohen-Tanugi, Johann
A1  - Costantin, D.
A1  - Cutini, S.
A1  - de Palma, F.
A1  - Di Lalla, N.
A1  - Di Mauro, M.
A1  - Di Venere, L.
A1  - Dominguez, A.
A1  - Favuzzi, C.
A1  - Fegan, S. J.
A1  - Franckowiak, Anna
A1  - Fukazawa, Yasushi
A1  - Funk, Stefan
A1  - Fusco, Piergiorgio
A1  - Gargano, Fabio
A1  - Gasparrini, Dario
A1  - Giglietto, Nicola
A1  - Giordano, F.
A1  - Giroletti, Marcello
A1  - Green, D.
A1  - Grenier, I. A.
A1  - Guillemot, L.
A1  - Guiriec, Sylvain
A1  - Hays, Elizabeth
A1  - Hewitt, John W.
A1  - Horan, D.
A1  - Johannesson, G.
A1  - Kensei, S.
A1  - Kuss, M.
A1  - Larsson, Stefan
A1  - Latronico, L.
A1  - Lemoine-Goumard, Marianne
A1  - Li, J.
A1  - Longo, Francesco
A1  - Loparco, Francesco
A1  - Lovellette, M. N.
A1  - Lubrano, Pasquale
A1  - Magill, Jeffrey D.
A1  - Maldera, Simone
A1  - Mazziotta, Mario Nicola
A1  - McEnery, J. E.
A1  - Michelson, P. F.
A1  - Mitthumsiri, W.
A1  - Mizuno, Tsunefumi
A1  - Monzani, Maria Elena
A1  - Morselli, Aldo
A1  - Moskalenko, Igor V.
A1  - Negro, M.
A1  - Nuss, E.
A1  - Ojha, R.
A1  - Omodei, Nicola
A1  - Orienti, M.
A1  - Orlando, E.
A1  - Palatiello, M.
A1  - Paliya, Vaidehi S.
A1  - Paneque, D.
A1  - Perkins, Jeremy S.
A1  - Persic, M.
A1  - Pesce-Rollins, Melissa
A1  - Petrosian, Vahe'
A1  - Piron, F.
A1  - Porter, Troy A.
A1  - Principe, G.
A1  - Raino, S.
A1  - Rando, Riccardo
A1  - Rani, B.
A1  - Razzano, Massimilano
A1  - Razzaque, Soebur
A1  - Reimer, A.
A1  - Reimer, Olaf
A1  - Reposeur, T.
A1  - Sgro, C.
A1  - Siskind, E. J.
A1  - Spandre, Gloria
A1  - Spinelli, P.
A1  - Suson, D. J.
A1  - Tajima, Hiroyasu
A1  - Thayer, J. B.
A1  - Thompson, David J.
A1  - Torres, Diego F.
A1  - Tosti, Gino
A1  - Troja, Eleonora
A1  - Valverde, J.
A1  - Vianello, Giacomo
A1  - Vogel, M.
A1  - Wood, K.
A1  - Yassine, M.
A1  - Alfaro, R.
A1  - Alvarez, C.
A1  - Alvarez, J. D.
A1  - Arceo, R.
A1  - Arteaga-Velazquez, J. C.
A1  - Rojas, D. Avila
A1  - Ayala Solares, H. A.
A1  - Becerril, A.
A1  - Belmont-Moreno, E.
A1  - BenZvi, S. Y.
A1  - Bernal, A.
A1  - Braun, J.
A1  - Brisbois, C.
A1  - Caballero-Mora, K. S.
A1  - Capistran, T.
A1  - Carraminana, A.
A1  - Casanova, Sabrina
A1  - Castillo, M.
A1  - Cotti, U.
A1  - Cotzomi, J.
A1  - Coutino de Leon, S.
A1  - De Leon, C.
A1  - De la Fuente, E.
A1  - Dichiara, S.
A1  - Dingus, B. L.
A1  - DuVernois, M. A.
A1  - Diaz-Velez, J. C.
A1  - Engel, K.
A1  - Enriquez-Rivera, O.
A1  - Fiorino, D. W.
A1  - Fleischhack, H.
A1  - Fraija, N.
A1  - Garcia-Gonzalez, J. A.
A1  - Garfias, F.
A1  - Gonzalez Munoz, A.
A1  - Gonzalez, M. M.
A1  - Goodman, J. A.
A1  - Hampel-Arias, Z.
A1  - Harding, J. P.
A1  - Hernandez, S.
A1  - Hernandez-Almada, A.
A1  - Hona, B.
A1  - Hueyotl-Zahuantitla, F.
A1  - Hui, C. M.
A1  - Huntemeyer, P.
A1  - Iriarte, A.
A1  - Jardin-Blicq, A.
A1  - Joshi, V.
A1  - Kaufmann, S.
A1  - Lara, A.
A1  - Lauer, R. J.
A1  - Lee, W. H.
A1  - Lennarz, D.
A1  - Leon Vargas, H.
A1  - Linnemann, J. T.
A1  - Longinotti, A. L.
A1  - Luis-Raya, G.
A1  - Luna-Garcia, R.
A1  - Lopez-Coto, R.
A1  - Malone, K.
A1  - Marinelli, S. S.
A1  - Martinez, O.
A1  - Martinez-Castellanos, I.
A1  - Martinez-Castro, J.
A1  - Martinez-Huerta, H.
A1  - Matthews, J. A.
A1  - Miranda-Romagnoli, P.
A1  - Moreno, E.
A1  - Mostafa, M.
A1  - Nayerhoda, A.
A1  - Nellen, L.
A1  - Newbold, M.
A1  - Nisa, M. U.
A1  - Noriega-Papaqui, R.
A1  - Pelayo, R.
A1  - Pretz, J.
A1  - Perez-Perez, E. G.
A1  - Ren, Z.
A1  - Rho, C. D.
A1  - Riviere, C.
A1  - Rosa-Gonzalez, D.
A1  - Rosenberg, M.
A1  - Ruiz-Velasco, E.
A1  - Salazar, H.
A1  - Greus, F. Salesa
A1  - Sandoval, A.
A1  - Schneider, M.
A1  - Arroyo, M. Seglar
A1  - Sinnis, G.
A1  - Smith, A. J.
A1  - Springer, R. W.
A1  - Surajbali, P.
A1  - Taboada, Ignacio
A1  - Tibolla, O.
A1  - Tollefson, K.
A1  - Torres, I.
A1  - Ukwatta, Tilan N.
A1  - Villasenor, L.
A1  - Weisgarber, T.
A1  - Westerhoff, Stefan
A1  - Wisher, I. G.
A1  - Wood, J.
A1  - Yapici, Tolga
A1  - Yodh, G.
A1  - Zepeda, A.
A1  - Zhou, H.
T1  - VERITAS and Fermi-LAT Observations of TeV Gamma-Ray Sources Discovered by HAWC in the 2HWC Catalog
JF  - The astrophysical journal : an international review of spectroscopy and astronomical physics
N2  - The High Altitude Water Cherenkov (HAWC) collaboration recently published their 2HWC catalog, listing 39 very high energy (VHE; >100 GeV) gamma-ray sources based on 507 days of observation. Among these, 19 sources are not associated with previously known teraelectronvolt (TeV) gamma-ray sources. We have studied 14 of these sources without known counterparts with VERITAS and Fermi-LAT. VERITAS detected weak gamma-ray emission in the 1 TeV-30 TeV band in the region of DA 495, a pulsar wind nebula coinciding with 2HWC J1953+294, confirming the discovery of the source by HAWC. We did not find any counterpart for the selected 14 new HAWC sources from our analysis of Fermi-LAT data for energies higher than 10 GeV. During the search, we detected gigaelectronvolt (GeV) gamma-ray emission coincident with a known TeV pulsar wind nebula, SNR G54.1+0.3 (VER J1930+188), and a 2HWC source, 2HWC J1930+188. The fluxes for isolated, steady sources in the 2HWC catalog are generally in good agreement with those measured by imaging atmospheric Cherenkov telescopes. However, the VERITAS fluxes for SNR G54.1+0.3, DA 495, and TeV J2032+4130 are lower than those measured by HAWC, and several new HAWC sources are not detected by VERITAS. This is likely due to a change in spectral shape, source extension, or the influence of diffuse emission in the source region.
KW  - gamma rays: general
Y1  - 2018
U6  - https://doi.org/10.3847/1538-4357/aade4e
SN  - 0004-637X
SN  - 1538-4357
VL  - 866
IS  - 1
PB  - IOP Publ. Ltd.
CY  - Bristol
ER  - 
TY  - JOUR
A1  - Archambault, S.
A1  - Arlen, T.
A1  - Aune, T.
A1  - Beilicke, M.
A1  - Benbow, W.
A1  - Bird, R.
A1  - Boettcher, Markus
A1  - Bouvier, A.
A1  - Buckley, J. H.
A1  - Bugaev, V.
A1  - Ciupik, L.
A1  - Collins-Hughes, E.
A1  - Connolly, M. P.
A1  - Cui, W.
A1  - Dickherber, R.
A1  - Dumm, J.
A1  - Errando, M.
A1  - Falcone, A.
A1  - Federici, Simone
A1  - Feng, Q.
A1  - Finley, J. P.
A1  - Fortson, L.
A1  - Furniss, A.
A1  - Galante, N.
A1  - Gall, D.
A1  - Garson, A. III.
A1  - Gillanders, G. H.
A1  - Griffin, S.
A1  - Grube, J.
A1  - Gusbar, C.
A1  - Gyuk, G.
A1  - Hanna, D.
A1  - Holder, J.
A1  - Hughes, G.
A1  - Kaaret, P.
A1  - Kertzman, M.
A1  - Khassen, Y.
A1  - Kieda, D.
A1  - Krawczynski, H.
A1  - Lamerato, A.
A1  - Lang, M. J.
A1  - Li, K.
A1  - Madhavan, A. S.
A1  - Maier, G.
A1  - Majumdar, P.
A1  - McArthur, S.
A1  - McCann, A.
A1  - Millis, J.
A1  - Moriarty, P.
A1  - Mukherjee, R.
A1  - Nieto, D.
A1  - Ong, R. A.
A1  - Orr, M.
A1  - Otte, A. N.
A1  - Park, N.
A1  - Perkins, J. S.
A1  - Pohl, Martin
A1  - Popkow, A.
A1  - Prokoph, H.
A1  - Quinn, J.
A1  - Ragan, K.
A1  - Reynolds, P. T.
A1  - Richards, G. T.
A1  - Roache, E.
A1  - Roustazadeh, P.
A1  - Saxon, D. B.
A1  - Sembroski, G. H.
A1  - Senturk, G. D.
A1  - Skole, C.
A1  - Staszak, D.
A1  - Telezhinsky, Igor O.
A1  - Tesic, G.
A1  - Theiling, M.
A1  - Varlotta, A.
A1  - Vassiliev, V. V.
A1  - Vincent, S.
A1  - Wakely, S. P.
A1  - Weinstein, A.
A1  - Welsing, R.
A1  - Williams, D. A.
A1  - Zitzer, B.
T1  - Test of models of the cosmic infrared background with multiwavelength  observations of the blazar 1ES 1218+30.4 IN 2009
JF  - The astrophysical journal : an international review of spectroscopy and astronomical physics
N2  - We present the results of a multi-wavelength campaign targeting the blazar 1ES 1218+30.4 with observations with the 1.3 m McGraw-Hill optical telescope, the Rossi X-ray Timing Explorer (RXTE), the Fermi Gamma-Ray Space Telescope, and the Very Energetic Radiation Imaging Telescope Array System (VERITAS). The RXTE and VERITAS observations were spread over a 13 day period and revealed clear evidence for flux variability, and a strong X-ray and gamma-ray flare on 2009 February 26 (MJD 54888). The campaign delivered a well-sampled broadband energy spectrum with simultaneous RXTE and VERITAS very high energy (VHE, > 100 GeV) observations, as well as contemporaneous optical and Fermi observations. The 1ES 1218+30.4 broadband energy spectrum-the first with simultaneous X-ray and VHE gamma-ray energy spectra-is of particular interest as the source is located at a high cosmological redshift for a VHE source (z = 0.182), leading to strong absorption of VHE gamma rays by photons from the optical/infrared extragalactic background light (EBL) via gamma VHE +gamma EBL -> e(+) e(-)pair-creation processes. We model the data with a one-zone synchrotron self-Compton (SSC) emission model and with the extragalactic absorption predicted by several recent EBL models. We find that the observations are consistent with the SSC scenario and all the EBL models considered in this work. We discuss observational and theoretical avenues to improve on the EBL constraints.
KW  - BL Lacertae objects: general
KW  - BL Lacertae objects: individual (1ES1218+30.4)
KW  - cosmic background radiation
KW  - diffuse radiation
KW  - galaxies: jets
KW  - gamma rays: galaxies
Y1  - 2014
U6  - https://doi.org/10.1088/0004-637X/788/2/158
SN  - 0004-637X
SN  - 1538-4357
VL  - 788
IS  - 2
PB  - IOP Publ. Ltd.
CY  - Bristol
ER  - 
TY  - JOUR
A1  - Warrington, Nicole
A1  - Beaumont, Robin
A1  - Horikoshi, Momoko
A1  - Day, Felix R.
A1  - Helgeland, Øyvind
A1  - Laurin, Charles
A1  - Bacelis, Jonas
A1  - Peng, Shouneng
A1  - Hao, Ke
A1  - Feenstra, Bjarke
A1  - Wood, Andrew R.
A1  - Mahajan, Anubha
A1  - Tyrrell, Jessica
A1  - Robertson, Neil R.
A1  - Rayner, N. William
A1  - Qiao, Zhen
A1  - Moen, Gunn-Helen
A1  - Vaudel, Marc
A1  - Marsit, Carmen
A1  - Chen, Jia
A1  - Nodzenski, Michael
A1  - Schnurr, Theresia M.
A1  - Zafarmand, Mohammad Hadi
A1  - Bradfield, Jonathan P.
A1  - Grarup, Niels
A1  - Kooijman, Marjolein N.
A1  - Li-Gao, Ruifang
A1  - Geller, Frank
A1  - Ahluwalia, Tarunveer Singh
A1  - Paternoster, Lavinia
A1  - Rueedi, Rico
A1  - Huikari, Ville
A1  - Hottenga, Jouke-Jan
A1  - Lyytikäinen, Leo-Pekka
A1  - Cavadino, Alana
A1  - Metrustry, Sarah
A1  - Cousminer, Diana L.
A1  - Wu, Ying
A1  - Thiering, Elisabeth Paula
A1  - Wang, Carol A.
A1  - Have, Christian Theil
A1  - Vilor-Tejedor, Natalia
A1  - Joshi, Peter K.
A1  - Painter, Jodie N.
A1  - Ntalla, Ioanna
A1  - Myhre, Ronny
A1  - Pitkänen, Niina
A1  - van Leeuwen, Elisabeth M.
A1  - Joro, Raimo
A1  - Lagou, Vasiliki
A1  - Richmond, Rebecca C.
A1  - Espinosa, Ana
A1  - Barton, Sheila J.
A1  - Inskip, Hazel M.
A1  - Holloway, John W.
A1  - Santa-Marina, Loreto
A1  - Estivill, Xavier
A1  - Ang, Wei
A1  - Marsh, Julie A.
A1  - Reichetzeder, Christoph
A1  - Marullo, Letizia
A1  - Hocher, Berthold
A1  - Lunetta, Kathryn L.
A1  - Murabito, Joanne M.
A1  - Relton, Caroline L.
A1  - Kogevinas, Manolis
A1  - Chatzi, Leda
A1  - Allard, Catherine
A1  - Bouchard, Luigi
A1  - Hivert, Marie-France
A1  - Zhang, Ge
A1  - Muglia, Louis J.
A1  - Heikkinen, Jani
A1  - Morgen, Camilla S.
A1  - van Kampen, Antoine H. C.
A1  - van Schaik, Barbera D. C.
A1  - Mentch, Frank D.
A1  - Langenberg, Claudia
A1  - Scott, Robert A.
A1  - Zhao, Jing Hua
A1  - Hemani, Gibran
A1  - Ring, Susan M.
A1  - Bennett, Amanda J.
A1  - Gaulton, Kyle J.
A1  - Fernandez-Tajes, Juan
A1  - van Zuydam, Natalie R.
A1  - Medina-Gomez, Carolina
A1  - de Haan, Hugoline G.
A1  - Rosendaal, Frits R.
A1  - Kutalik, Zoltán
A1  - Marques-Vidal, Pedro
A1  - Das, Shikta
A1  - Willemsen, Gonneke
A1  - Mbarek, Hamdi
A1  - Müller-Nurasyid, Martina
A1  - Standl, Marie
A1  - Appel, Emil V. R.
A1  - Fonvig, Cilius Esmann
A1  - Trier, Caecilie
A1  - van Beijsterveldt, Catharina E. M.
A1  - Murcia, Mario
A1  - Bustamante, Mariona
A1  - Bonàs-Guarch, Sílvia
A1  - Hougaard, David M.
A1  - Mercader, Josep M.
A1  - Linneberg, Allan
A1  - Schraut, Katharina E.
A1  - Lind, Penelope A.
A1  - Medland, Sarah Elizabeth
A1  - Shields, Beverley M.
A1  - Knight, Bridget A.
A1  - Chai, Jin-Fang
A1  - Panoutsopoulou, Kalliope
A1  - Bartels, Meike
A1  - Sánchez, Friman
A1  - Stokholm, Jakob
A1  - Torrents, David
A1  - Vinding, Rebecca K.
A1  - Willems, Sara M.
A1  - Atalay, Mustafa
A1  - Chawes, Bo L.
A1  - Kovacs, Peter
A1  - Prokopenko, Inga
A1  - Tuke, Marcus A.
A1  - Yaghootkar, Hanieh
A1  - Ruth, Katherine S.
A1  - Jones, Samuel E.
A1  - Loh, Po-Ru
A1  - Murray, Anna
A1  - Weedon, Michael N.
A1  - Tönjes, Anke
A1  - Stumvoll, Michael
A1  - Michaelsen, Kim Fleischer
A1  - Eloranta, Aino-Maija
A1  - Lakka, Timo A.
A1  - van Duijn, Cornelia M.
A1  - Kiess, Wieland
A1  - Koerner, Antje
A1  - Niinikoski, Harri
A1  - Pahkala, Katja
A1  - Raitakari, Olli T.
A1  - Jacobsson, Bo
A1  - Zeggini, Eleftheria
A1  - Dedoussis, George V.
A1  - Teo, Yik-Ying
A1  - Saw, Seang-Mei
A1  - Montgomery, Grant W.
A1  - Campbell, Harry
A1  - Wilson, James F.
A1  - Vrijkotte, Tanja G. M.
A1  - Vrijheid, Martine
A1  - de Geus, Eco J. C. N.
A1  - Hayes, M. Geoffrey
A1  - Kadarmideen, Haja N.
A1  - Holm, Jens-Christian
A1  - Beilin, Lawrence J.
A1  - Pennell, Craig E.
A1  - Heinrich, Joachim
A1  - Adair, Linda S.
A1  - Borja, Judith B.
A1  - Mohlke, Karen L.
A1  - Eriksson, Johan G.
A1  - Widen, Elisabeth E.
A1  - Hattersley, Andrew T.
A1  - Spector, Tim D.
A1  - Kaehoenen, Mika
A1  - Viikari, Jorma S.
A1  - Lehtimaeki, Terho
A1  - Boomsma, Dorret I.
A1  - Sebert, Sylvain
A1  - Vollenweider, Peter
A1  - Sorensen, Thorkild I. A.
A1  - Bisgaard, Hans
A1  - Bonnelykke, Klaus
A1  - Murray, Jeffrey C.
A1  - Melbye, Mads
A1  - Nohr, Ellen A.
A1  - Mook-Kanamori, Dennis O.
A1  - Rivadeneira, Fernando
A1  - Hofman, Albert
A1  - Felix, Janine F.
A1  - Jaddoe, Vincent W. V.
A1  - Hansen, Torben
A1  - Pisinger, Charlotta
A1  - Vaag, Allan A.
A1  - Pedersen, Oluf
A1  - Uitterlinden, Andre G.
A1  - Jarvelin, Marjo-Riitta
A1  - Power, Christine
A1  - Hypponen, Elina
A1  - Scholtens, Denise M.
A1  - Lowe, William L.
A1  - Smith, George Davey
A1  - Timpson, Nicholas J.
A1  - Morris, Andrew P.
A1  - Wareham, Nicholas J.
A1  - Hakonarson, Hakon
A1  - Grant, Struan F. A.
A1  - Frayling, Timothy M.
A1  - Lawlor, Debbie A.
A1  - Njolstad, Pal R.
A1  - Johansson, Stefan
A1  - Ong, Ken K.
A1  - McCarthy, Mark I.
A1  - Perry, John R. B.
A1  - Evans, David M.
A1  - Freathy, Rachel M.
T1  - Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors
JF  - Nature genetics
N2  - Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.
Y1  - 2019
SN  - 1061-4036
SN  - 1546-1718
VL  - 51
IS  - 5
SP  - 804
EP  - +
PB  - Nature Publ. Group
CY  - New York
ER  - 
TY  - JOUR
A1  - Middeldorp, Christel M.
A1  - Mahajan, Anubha
A1  - Horikoshi, Momoko
A1  - Robertson, Neil R.
A1  - Beaumont, Robin N.
A1  - Bradfield, Jonathan P.
A1  - Bustamante, Mariona
A1  - Cousminer, Diana L.
A1  - Day, Felix R.
A1  - De Silva, N. Maneka
A1  - Guxens, Monica
A1  - Mook-Kanamori, Dennis O.
A1  - St Pourcain, Beate
A1  - Warrington, Nicole M.
A1  - Adair, Linda S.
A1  - Ahlqvist, Emma
A1  - Ahluwalia, Tarunveer Singh
A1  - Almgren, Peter
A1  - Ang, Wei
A1  - Atalay, Mustafa
A1  - Auvinen, Juha
A1  - Bartels, Meike
A1  - Beckmann, Jacques S.
A1  - Bilbao, Jose Ramon
A1  - Bond, Tom
A1  - Borja, Judith B.
A1  - Cavadino, Alana
A1  - Charoen, Pimphen
A1  - Chen, Zhanghua
A1  - Coin, Lachlan
A1  - Cooper, Cyrus
A1  - Curtin, John A.
A1  - Custovic, Adnan
A1  - Das, Shikta
A1  - Davies, Gareth E.
A1  - Dedoussis, George V.
A1  - Duijts, Liesbeth
A1  - Eastwood, Peter R.
A1  - Eliasen, Anders U.
A1  - Elliott, Paul
A1  - Eriksson, Johan G.
A1  - Estivill, Xavier
A1  - Fadista, Joao
A1  - Fedko, Iryna O.
A1  - Frayling, Timothy M.
A1  - Gaillard, Romy
A1  - Gauderman, W. James
A1  - Geller, Frank
A1  - Gilliland, Frank
A1  - Gilsanz, Vincente
A1  - Granell, Raquel
A1  - Grarup, Niels
A1  - Groop, Leif
A1  - Hadley, Dexter
A1  - Hakonarson, Hakon
A1  - Hansen, Torben
A1  - Hartman, Catharina A.
A1  - Hattersley, Andrew T.
A1  - Hayes, M. Geoffrey
A1  - Hebebrand, Johannes
A1  - Heinrich, Joachim
A1  - Helgeland, Oyvind
A1  - Henders, Anjali K.
A1  - Henderson, John
A1  - Henriksen, Tine B.
A1  - Hirschhorn, Joel N.
A1  - Hivert, Marie-France
A1  - Hocher, Berthold
A1  - Holloway, John W.
A1  - Holt, Patrick
A1  - Hottenga, Jouke-Jan
A1  - Hypponen, Elina
A1  - Iniguez, Carmen
A1  - Johansson, Stefan
A1  - Jugessur, Astanand
A1  - Kahonen, Mika
A1  - Kalkwarf, Heidi J.
A1  - Kaprio, Jaakko
A1  - Karhunen, Ville
A1  - Kemp, John P.
A1  - Kerkhof, Marjan
A1  - Koppelman, Gerard H.
A1  - Korner, Antje
A1  - Kotecha, Sailesh
A1  - Kreiner-Moller, Eskil
A1  - Kulohoma, Benard
A1  - Kumar, Ashish
A1  - Kutalik, Zoltan
A1  - Lahti, Jari
A1  - Lappe, Joan M.
A1  - Larsson, Henrik
A1  - Lehtimaki, Terho
A1  - Lewin, Alexandra M.
A1  - Li, Jin
A1  - Lichtenstein, Paul
A1  - Lindgren, Cecilia M.
A1  - Lindi, Virpi
A1  - Linneberg, Allan
A1  - Liu, Xueping
A1  - Liu, Jun
A1  - Lowe, William L.
A1  - Lundstrom, Sebastian
A1  - Lyytikainen, Leo-Pekka
A1  - Ma, Ronald C. W.
A1  - Mace, Aurelien
A1  - Magi, Reedik
A1  - Magnus, Per
A1  - Mamun, Abdullah A.
A1  - Mannikko, Minna
A1  - Martin, Nicholas G.
A1  - Mbarek, Hamdi
A1  - McCarthy, Nina S.
A1  - Medland, Sarah E.
A1  - Melbye, Mads
A1  - Melen, Erik
A1  - Mohlke, Karen L.
A1  - Monnereau, Claire
A1  - Morgen, Camilla S.
A1  - Morris, Andrew P.
A1  - Murray, Jeffrey C.
A1  - Myhre, Ronny
A1  - Najman, Jackob M.
A1  - Nivard, Michel G.
A1  - Nohr, Ellen A.
A1  - Nolte, Ilja M.
A1  - Ntalla, Ioanna
A1  - Oberfield, Sharon E.
A1  - Oken, Emily
A1  - Oldehinkel, Albertine J.
A1  - Pahkala, Katja
A1  - Palviainen, Teemu
A1  - Panoutsopoulou, Kalliope
A1  - Pedersen, Oluf
A1  - Pennell, Craig E.
A1  - Pershagen, Goran
A1  - Pitkanen, Niina
A1  - Plomin, Robert
A1  - Power, Christine
A1  - Prasad, Rashmi B.
A1  - Prokopenko, Inga
A1  - Pulkkinen, Lea
A1  - Raikkonen, Katri
A1  - Raitakari, Olli T.
A1  - Reynolds, Rebecca M.
A1  - Richmond, Rebecca C.
A1  - Rivadeneira, Fernando
A1  - Rodriguez, Alina
A1  - Rose, Richard J.
A1  - Salem, Rany
A1  - Santa-Marina, Loreto
A1  - Saw, Seang-Mei
A1  - Schnurr, Theresia M.
A1  - Scott, James G.
A1  - Selzam, Saskia
A1  - Shepherd, John A.
A1  - Simpson, Angela
A1  - Skotte, Line
A1  - Sleiman, Patrick M. A.
A1  - Snieder, Harold
A1  - Sorensen, Thorkild I. A.
A1  - Standl, Marie
A1  - Steegers, Eric A. P.
A1  - Strachan, David P.
A1  - Straker, Leon
A1  - Strandberg, Timo
A1  - Taylor, Michelle
A1  - Teo, Yik-Ying
A1  - Thiering, Elisabeth
A1  - Torrent, Maties
A1  - Tyrrell, Jessica
A1  - Uitterlinden, Andre G.
A1  - van Beijsterveldt, Toos
A1  - van der Most, Peter J.
A1  - van Duijn, Cornelia M.
A1  - Viikari, Jorma
A1  - Vilor-Tejedor, Natalia
A1  - Vogelezang, Suzanne
A1  - Vonk, Judith M.
A1  - Vrijkotte, Tanja G. M.
A1  - Vuoksimaa, Eero
A1  - Wang, Carol A.
A1  - Watkins, William J.
A1  - Wichmann, H-Erich
A1  - Willemsen, Gonneke
A1  - Williams, Gail M.
A1  - Wilson, James F.
A1  - Wray, Naomi R.
A1  - Xu, Shujing
A1  - Xu, Cheng-Jian
A1  - Yaghootkar, Hanieh
A1  - Yi, Lu
A1  - Zafarmand, Mohammad Hadi
A1  - Zeggini, Eleftheria
A1  - Zemel, Babette S.
A1  - Hinney, Anke
A1  - Lakka, Timo A.
A1  - Whitehouse, Andrew J. O.
A1  - Sunyer, Jordi
A1  - Widen, Elisabeth E.
A1  - Feenstra, Bjarke
A1  - Sebert, Sylvain
A1  - Jacobsson, Bo
A1  - Njolstad, Pal R.
A1  - Stoltenberg, Camilla
A1  - Smith, George Davey
A1  - Lawlor, Debbie A.
A1  - Paternoster, Lavinia
A1  - Timpson, Nicholas J.
A1  - Ong, Ken K.
A1  - Bisgaard, Hans
A1  - Bonnelykke, Klaus
A1  - Jaddoe, Vincent W. V.
A1  - Tiemeier, Henning
A1  - Jarvelin, Marjo-Riitta
A1  - Evans, David M.
A1  - Perry, John R. B.
A1  - Grant, Struan F. A.
A1  - Boomsma, Dorret I.
A1  - Freathy, Rachel M.
A1  - McCarthy, Mark I.
A1  - Felix, Janine F.
T1  - The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia
BT  - design, results and future prospects
JF  - European journal of epidemiology
N2  - The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
KW  - Genetics
KW  - Consortium
KW  - Childhood traits and disorders
KW  - Longitudinal
Y1  - 2019
U6  - https://doi.org/10.1007/s10654-019-00502-9
SN  - 0393-2990
SN  - 1573-7284
VL  - 34
IS  - 3
SP  - 279
EP  - 300
PB  - Springer
CY  - Dordrecht
ER  - 
TY  - JOUR
A1  - Yang, Jie
A1  - Zhu, Xiaolei
A1  - Wolf, Thomas J. A.
A1  - Li, Zheng
A1  - Nunes, João Pedro Figueira
A1  - Coffee, Ryan
A1  - Cryan, James P.
A1  - Gühr, Markus
A1  - Hegazy, Kareem
A1  - Heinz, Tony F.
A1  - Jobe, Keith
A1  - Li, Renkai
A1  - Shen, Xiaozhe
A1  - Veccione, Theodore
A1  - Weathersby, Stephen
A1  - Wilkin, Kyle J.
A1  - Yoneda, Charles
A1  - Zheng, Qiang
A1  - Martinez, Todd J.
A1  - Centurion, Martin
A1  - Wang, Xijie
T1  - Imaging CF3I conical intersection and photodissociation dynamics with ultrafast electron diffraction
JF  - Science
N2  - Conical intersections play a critical role in excited-state dynamics of polyatomic molecules because they govern the reaction pathways of many nonadiabatic processes. However, ultrafast probes have lacked sufficient spatial resolution to image wave-packet trajectories through these intersections directly. Here, we present the simultaneous experimental characterization of one-photon and two-photon excitation channels in isolated CF3I molecules using ultrafast gas-phase electron diffraction. In the two-photon channel, we have mapped out the real-space trajectories of a coherent nuclear wave packet, which bifurcates onto two potential energy surfaces when passing through a conical intersection. In the one-photon channel, we have resolved excitation of both the umbrella and the breathing vibrational modes in the CF3 fragment in multiple nuclear dimensions. These findings benchmark and validate ab initio nonadiabatic dynamics calculations.
Y1  - 2018
U6  - https://doi.org/10.1126/science.aat0049
SN  - 0036-8075
SN  - 1095-9203
VL  - 361
IS  - 6397
SP  - 64
EP  - 67
PB  - American Assoc. for the Advancement of Science
CY  - Washington
ER  - 
TY  - JOUR
A1  - Hocher, Berthold
A1  - Lu, Yong-Ping
A1  - Reichetzeder, Christoph
A1  - Zhang, Xiaoli
A1  - Tsuprykov, Oleg
A1  - Rahnenführer, Jan
A1  - Xie, Li
A1  - Li, Jian
A1  - Hu, Liang
A1  - Krämer, Bernhard K.
A1  - Hasan, Ahmed A.
T1  - Paternal eNOS deficiency in mice affects glucose homeostasis and liver glycogen in male offspring without inheritance of eNOS deficiency itself
JF  - Diabetologia
N2  - Aims/hypothesis It was shown that maternal endothelial nitric oxide synthase (eNOS) deficiency causes fatty liver disease and numerically lower fasting glucose in female wild-type offspring, suggesting that parental genetic variants may influence the offspring's phenotype via epigenetic modifications in the offspring despite the absence of a primary genetic defect. The aim of the current study was to analyse whether paternal eNOS deficiency may cause the same phenotype as seen with maternal eNOS deficiency. Methods Heterozygous (+/-) male eNOS (Nos3) knockout mice or wild-type male mice were bred with female wild-type mice. The phenotype of wild-type offspring of heterozygous male eNOS knockout mice was compared with offspring from wild-type parents. Results Global sperm DNA methylation decreased and sperm microRNA pattern altered substantially. Fasting glucose and liver glycogen storage were increased when analysing wild-type male and female offspring of +/- eNOS fathers. Wild-type male but not female offspring of +/- eNOS fathers had increased fasting insulin and increased insulin after glucose load. Analysing candidate genes for liver fat and carbohydrate metabolism revealed that the expression of genes encoding glucocorticoid receptor (Gr; also known as Nr3c1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc1a; also known as Ppargc1a) was increased while DNA methylation of Gr exon 1A and Pgc1a promoter was decreased in the liver of male wild-type offspring of +/- eNOS fathers. The endocrine pancreas in wild-type offspring was not affected. <br /> Conclusions/interpretation Our study suggests that paternal genetic defects such as eNOS deficiency may alter the epigenome of the sperm without transmission of the paternal genetic defect itself. In later life wild-type male offspring of +/- eNOS fathers developed increased fasting insulin and increased insulin after glucose load. These effects are associated with increased Gr and Pgc1a gene expression due to altered methylation of these genes.
KW  - eNOS
KW  - Glucocorticoid receptor
KW  - Insulin resistance
KW  - Paternal programming;
KW  - PGC1a
Y1  - 2022
U6  - https://doi.org/10.1007/s00125-022-05700-x
SN  - 0012-186X
SN  - 1432-0428
VL  - 65
IS  - 7
SP  - 1222
EP  - 1236
PB  - Springer
CY  - New York
ER  - 
TY  - JOUR
A1  - Chan, Lili
A1  - Chaudhary, Kumardeep
A1  - Saha, Aparna
A1  - Chauhan, Kinsuk
A1  - Vaid, Akhil
A1  - Zhao, Shan
A1  - Paranjpe, Ishan
A1  - Somani, Sulaiman
A1  - Richter, Felix
A1  - Miotto, Riccardo
A1  - Lala, Anuradha
A1  - Kia, Arash
A1  - Timsina, Prem
A1  - Li, Li
A1  - Freeman, Robert
A1  - Chen, Rong
A1  - Narula, Jagat
A1  - Just, Allan C.
A1  - Horowitz, Carol
A1  - Fayad, Zahi
A1  - Cordon-Cardo, Carlos
A1  - Schadt, Eric
A1  - Levin, Matthew A.
A1  - Reich, David L.
A1  - Fuster, Valentin
A1  - Murphy, Barbara
A1  - He, John C.
A1  - Charney, Alexander W.
A1  - Böttinger, Erwin
A1  - Glicksberg, Benjamin
A1  - Coca, Steven G.
A1  - Nadkarni, Girish N.
T1  - AKI in hospitalized patients with COVID-19
JF  - Journal of the American Society of Nephrology : JASN
N2  - Background:
Early reports indicate that AKI is common among patients with coronavirus disease 2019 (COVID-19) and associatedwith worse outcomes. However, AKI among hospitalized patients with COVID19 in the United States is not well described. 

Methods:
This retrospective, observational study involved a review of data from electronic health records of patients aged >= 18 years with laboratory-confirmed COVID-19 admitted to the Mount Sinai Health System from February 27 to May 30, 2020. We describe the frequency of AKI and dialysis requirement, AKI recovery, and adjusted odds ratios (aORs) with mortality. 

Results:
Of 3993 hospitalized patients with COVID-19, AKI occurred in 1835 (46%) patients; 347 (19%) of the patientswith AKI required dialysis. The proportionswith stages 1, 2, or 3 AKIwere 39%, 19%, and 42%, respectively. A total of 976 (24%) patients were admitted to intensive care, and 745 (76%) experienced AKI. Of the 435 patients with AKI and urine studies, 84% had proteinuria, 81% had hematuria, and 60% had leukocyturia. Independent predictors of severe AKI were CKD, men, and higher serum potassium at admission. In-hospital mortality was 50% among patients with AKI versus 8% among those without AKI (aOR, 9.2; 95% confidence interval, 7.5 to 11.3). Of survivors with AKI who were discharged, 35% had not recovered to baseline kidney function by the time of discharge. An additional 28 of 77 (36%) patients who had not recovered kidney function at discharge did so on posthospital follow-up. 

Conclusions:
AKI is common among patients hospitalized with COVID-19 and is associated with high mortality. Of all patients with AKI, only 30% survived with recovery of kidney function by the time of discharge.
KW  - acute renal failure
KW  - clinical nephrology
KW  - dialysis
KW  - COVID-19
Y1  - 2021
U6  - https://doi.org/10.1681/ASN.2020050615
SN  - 1046-6673
SN  - 1533-3450
VL  - 32
IS  - 1
SP  - 151
EP  - 160
PB  - American Society of Nephrology
CY  - Washington
ER  - 
TY  - JOUR
A1  - Arnison, Paul G.
A1  - Bibb, Mervyn J.
A1  - Bierbaum, Gabriele
A1  - Bowers, Albert A.
A1  - Bugni, Tim S.
A1  - Bulaj, Grzegorz
A1  - Camarero, Julio A.
A1  - Campopiano, Dominic J.
A1  - Challis, Gregory L.
A1  - Clardy, Jon
A1  - Cotter, Paul D.
A1  - Craik, David J.
A1  - Dawson, Michael
A1  - Dittmann-Thünemann, Elke
A1  - Donadio, Stefano
A1  - Dorrestein, Pieter C.
A1  - Entian, Karl-Dieter
A1  - Fischbach, Michael A.
A1  - Garavelli, John S.
A1  - Goeransson, Ulf
A1  - Gruber, Christian W.
A1  - Haft, Daniel H.
A1  - Hemscheidt, Thomas K.
A1  - Hertweck, Christian
A1  - Hill, Colin
A1  - Horswill, Alexander R.
A1  - Jaspars, Marcel
A1  - Kelly, Wendy L.
A1  - Klinman, Judith P.
A1  - Kuipers, Oscar P.
A1  - Link, A. James
A1  - Liu, Wen
A1  - Marahiel, Mohamed A.
A1  - Mitchell, Douglas A.
A1  - Moll, Gert N.
A1  - Moore, Bradley S.
A1  - Mueller, Rolf
A1  - Nair, Satish K.
A1  - Nes, Ingolf F.
A1  - Norris, Gillian E.
A1  - Olivera, Baldomero M.
A1  - Onaka, Hiroyasu
A1  - Patchett, Mark L.
A1  - Piel, Jörn
A1  - Reaney, Martin J. T.
A1  - Rebuffat, Sylvie
A1  - Ross, R. Paul
A1  - Sahl, Hans-Georg
A1  - Schmidt, Eric W.
A1  - Selsted, Michael E.
A1  - Severinov, Konstantin
A1  - Shen, Ben
A1  - Sivonen, Kaarina
A1  - Smith, Leif
A1  - Stein, Torsten
A1  - Suessmuth, Roderich D.
A1  - Tagg, John R.
A1  - Tang, Gong-Li
A1  - Truman, Andrew W.
A1  - Vederas, John C.
A1  - Walsh, Christopher T.
A1  - Walton, Jonathan D.
A1  - Wenzel, Silke C.
A1  - Willey, Joanne M.
A1  - van der Donk, Wilfred A.
T1  - Ribosomally synthesized and post-translationally modified peptide natural products overview and recommendations for a universal nomenclature
JF  - Natural product reports : a journal of current developments in bio-organic chemistry
N2  - This review presents recommended nomenclature for the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs), a rapidly growing class of natural products. The current knowledge regarding the biosynthesis of the >20 distinct compound classes is also reviewed, and commonalities are discussed.
Y1  - 2013
U6  - https://doi.org/10.1039/c2np20085f
SN  - 0265-0568
VL  - 30
IS  - 1
SP  - 108
EP  - 160
PB  - Royal Society of Chemistry
CY  - Cambridge
ER  - 
TY  - JOUR
A1  - Aldoretta, E. J.
A1  - St-Louis, N.
A1  - Richardson, N. D.
A1  - Moffat, Anthony F. J.
A1  - Eversberg, T.
A1  - Hill, G. M.
A1  - Shenar, Tomer
A1  - Artigau, E.
A1  - Gauza, B.
A1  - Knapen, J. H.
A1  - Kubat, Jiří
A1  - Kubatova, Brankica
A1  - Maltais-Tariant, R.
A1  - Munoz, M.
A1  - Pablo, H.
A1  - Ramiaramanantsoa, T.
A1  - Richard-Laferriere, A.
A1  - Sablowski, D. P.
A1  - Simon-Diaz, S.
A1  - St-Jean, L.
A1  - Bolduan, F.
A1  - Dias, F. M.
A1  - Dubreuil, P.
A1  - Fuchs, D.
A1  - Garrel, T.
A1  - Grutzeck, G.
A1  - Hunger, T.
A1  - Kuesters, D.
A1  - Langenbrink, M.
A1  - Leadbeater, R.
A1  - Li, D.
A1  - Lopez, A.
A1  - Mauclaire, B.
A1  - Moldenhawer, T.
A1  - Potter, M.
A1  - dos Santos, E. M.
A1  - Schanne, L.
A1  - Schmidt, J.
A1  - Sieske, H.
A1  - Strachan, J.
A1  - Stinner, E.
A1  - Stinner, P.
A1  - Stober, B.
A1  - Strandbaek, K.
A1  - Syder, T.
A1  - Verilhac, D.
A1  - Waldschlaeger, U.
A1  - Weiss, D.
A1  - Wendt, A.
T1  - An extensive spectroscopic time series of three Wolf-Rayet stars - I. The lifetime of large-scale structures in the wind of WR 134
JF  - Monthly notices of the Royal Astronomical Society
N2  - During the summer of 2013, a 4-month spectroscopic campaign took place to observe the variabilities in three Wolf-Rayet stars. The spectroscopic data have been analysed for WR 134 (WN6b), to better understand its behaviour and long-term periodicity, which we interpret as arising from corotating interaction regions (CIRs) in the wind. By analysing the variability of the He ii lambda 5411 emission line, the previously identified period was refined to P = 2.255 +/- 0.008 (s.d.) d. The coherency time of the variability, which we associate with the lifetime of the CIRs in the wind, was deduced to be 40 +/- 6 d, or similar to 18 cycles, by cross-correlating the variability patterns as a function of time. When comparing the phased observational grey-scale difference images with theoretical grey-scales previously calculated from models including CIRs in an optically thin stellar wind, we find that two CIRs were likely present. A separation in longitude of Delta I center dot a parts per thousand integral 90A degrees was determined between the two CIRs and we suggest that the different maximum velocities that they reach indicate that they emerge from different latitudes. We have also been able to detect observational signatures of the CIRs in other spectral lines (C iv lambda lambda 5802,5812 and He i lambda 5876). Furthermore, a DAC was found to be present simultaneously with the CIR signatures detected in the He i lambda 5876 emission line which is consistent with the proposed geometry of the large-scale structures in the wind. Small-scale structures also show a presence in the wind, simultaneously with the larger scale structures, showing that they do in fact co-exist.
KW  - instabilities
KW  - methods: data analysis
KW  - techniques: spectroscopic
KW  - stars: individual: WR 134
KW  - stars: massive
KW  - stars: Wolf-Rayet
Y1  - 2016
U6  - https://doi.org/10.1093/mnras/stw1188
SN  - 0035-8711
SN  - 1365-2966
VL  - 460
SP  - 3407
EP  - 3417
PB  - Oxford Univ. Press
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Levermann, Anders
A1  - Winkelmann, Ricarda
A1  - Nowicki, S.
A1  - Fastook, J. L.
A1  - Frieler, Katja
A1  - Greve, R.
A1  - Hellmer, H. H.
A1  - Martin, M. A.
A1  - Meinshausen, Malte
A1  - Mengel, Matthias
A1  - Payne, A. J.
A1  - Pollard, D.
A1  - Sato, T.
A1  - Timmermann, R.
A1  - Wang, Wei Li
A1  - Bindschadler, Robert A.
T1  - Projecting antarctic ice discharge using response functions from SeaRISE ice-sheet models
JF  - Earth system dynamics
N2  - The largest uncertainty in projections of future sea-level change results from the potentially changing dynamical ice discharge from Antarctica. Basal ice-shelf melting induced by a warming ocean has been identified as a major cause for additional ice flow across the grounding line. Here we attempt to estimate the uncertainty range of future ice discharge from Antarctica by combining uncertainty in the climatic forcing, the oceanic response and the ice-sheet model response. The uncertainty in the global mean temperature increase is obtained from historically constrained emulations with the MAGICC-6.0 (Model for the Assessment of Greenhouse gas Induced Climate Change) model. The oceanic forcing is derived from scaling of the subsurface with the atmospheric warming from 19 comprehensive climate models of the Coupled Model Intercomparison Project (CMIP-5) and two ocean models from the EU-project Ice2Sea. The dynamic ice-sheet response is derived from linear response functions for basal ice-shelf melting for four different Antarctic drainage regions using experiments from the Sea-level Response to Ice Sheet Evolution (SeaRISE) intercomparison project with five different Antarctic ice-sheet models. The resulting uncertainty range for the historic Antarctic contribution to global sea-level rise from 1992 to 2011 agrees with the observed contribution for this period if we use the three ice-sheet models with an explicit representation of ice-shelf dynamics and account for the time-delayed warming of the oceanic subsurface compared to the surface air temperature. The median of the additional ice loss for the 21st century is computed to 0.07 m (66% range: 0.02-0.14 m; 90% range: 0.0-0.23 m) of global sea-level equivalent for the low-emission RCP-2.6 (Representative Concentration Pathway) scenario and 0.09 m (66% range: 0.04-0.21 m; 90% range: 0.01-0.37 m) for the strongest RCP-8.5. Assuming no time delay between the atmospheric warming and the oceanic subsurface, these values increase to 0.09 m (66% range: 0.04-0.17 m; 90% range: 0.02-0.25 m) for RCP-2.6 and 0.15 m (66% range: 0.07-0.28 m; 90% range: 0.04-0.43 m) for RCP-8.5. All probability distributions are highly skewed towards high values. The applied ice-sheet models are coarse resolution with limitations in the representation of grounding-line motion. Within the constraints of the applied methods, the uncertainty induced from different ice-sheet models is smaller than that induced by the external forcing to the ice sheets.
Y1  - 2014
U6  - https://doi.org/10.5194/esd-5-271-2014
SN  - 2190-4979
SN  - 2190-4987
VL  - 5
IS  - 2
SP  - 271
EP  - 293
PB  - Copernicus
CY  - Göttingen
ER  - 
TY  - JOUR
A1  - Wolbern, I
A1  - Jacob, A. W. B.
A1  - Blake, T. A.
A1  - Kind, Rainer
A1  - Li, X
A1  - Yuan, X. H
A1  - Duennebier, F
A1  - Weber, Michael H.
T1  - Deep origin of the Hawaiian tilted plume conduit derived from receiver functions
N2  - We employ P to S converted waveforms to investigate effects of the hot mantle plume on seismic discontinuities of the crust and upper mantle. We observe the Moho at depths between 13 and 17 km, regionally covered by a strong shallow intracrustal converted phase. Coherent phases on the transverse component indicate either dipping interfaces, 3- D heterogeneities or lower crustal anisotropy. We find anomalies related to discontinuities in the upper mantle down to the transition zone evidently related to the hot mantle plume. Lithospheric thinning is confirmed in greater detail than previously reported by Li et al., and we determine the dimensions of the low-velocity zone within the asthenosphere with greater accuracy. Our study mainly focuses on the temperature-pressure dependent discontinuities of the upper mantle transition zone. Effects of the hot diapir on the depths of mineral phase transitions are verified at both major interfaces at 410 and 660 km. We determine a plume radius of about 200 km at the 660 km discontinuity with a core zone of about 120 km radius. The plume conduit is located southwest of Big Island. A conduit tilted in the northeast direction is required in the upper mantle to explain the observations. The determined positions of deflections of the discontinuities support the hypothesis of decoupled upper and lower mantle convection
Y1  - 2006
UR  - http://onlinelibrary.wiley.com/doi/10.1111/j.1365-246X.2006.03036.x/full
U6  - https://doi.org/10.1111/j.1365-246X.2006.03036.x
ER  - 
TY  - JOUR
A1  - Patterson, Jenelle A.
A1  - He, Hai
A1  - Folz, Jacob S.
A1  - Li, Qiang
A1  - Wilson, Mark A.
A1  - Fiehn, Oliver
A1  - Bruner, Steven D.
A1  - Bar-Even, Arren
A1  - Hanson, Andrew D.
T1  - Thioproline formation as a driver of formaldehyde toxicity in Escherichia coli
JF  - Biochemical Journal
N2  - Formaldehyde (HCHO) is a reactive carbonyl compound that formylates and cross-links proteins, DNA, and small molecules. It is of specific concern as a toxic intermediate in the design of engineered pathways involving methanol oxidation or formate reduction. The interest in engineering these pathways is not, however, matched by engineering-relevant information on precisely why HCHO is toxic or on what damage-control mechanisms cells deploy to manage HCHO toxicity. The only well-defined mechanism for managing HCHO toxicity is formaldehyde dehydrogenase-mediated oxidation to formate, which is counterproductive if HCHO is a desired pathway intermediate. We therefore sought alternative HCHO damage-control mechanisms via comparative genomic analysis. This analysis associated homologs of the Escherichia coli pepP gene with HCHO-related one-carbon metabolism. Furthermore, deleting pepP increased the sensitivity of E. coli to supplied HCHO but not other carbonyl compounds. PepP is a proline aminopeptidase that cleaves peptides of the general formula X-Pro-Y, yielding X + Pro-Y. HCHO is known to react spontaneously with cysteine to form the close proline analog thioproline (thiazolidine-4-carboxylate), which is incorporated into proteins and hence into proteolytic peptides. We therefore hypothesized that certain thioproline-containing peptides are toxic and that PepP cleaves these aberrant peptides. Supporting this hypothesis, PepP cleaved the model peptide Ala-thioproline-Ala as efficiently as Ala-Pro-Ala in vitro and in vivo, and deleting pepP increased sensitivity to supplied thioproline. Our data thus (i) provide biochemical genetic evidence that thioproline formation contributes substantially to HCHO toxicity and (ii) make PepP a candidate damage-control enzyme for engineered pathways having HCHO as an intermediate.
KW  - formaldehyde
KW  - thiazolidine-4-carboxylic acid
KW  - thioproline
KW  - Xaa-Pro aminopeptidase
Y1  - 2020
U6  - https://doi.org/10.1042/BCJ20200198
SN  - 1470-8728
SN  - 0006-2936
VL  - 477
IS  - 9
SP  - 1745
EP  - 1757
PB  - Portland Press
CY  - London
ER  - 
TY  - JOUR
A1  - Lorenz, Bernd
A1  - Miller, A. J.
A1  - Hochheimer, H. D.
A1  - Hönle, W.
A1  - Li, T.
A1  - Ruoff, A. L.
T1  - High pressure phase transition in tetramethylammonium tetra bromocuprate
Y1  - 1995
ER  - 
TY  - JOUR
A1  - Xia, Haiyan
A1  - Cao, Yun
A1  - Dai, Xiaoman
A1  - Marelja, Zvonimir
A1  - Zhou, Di
A1  - Mo, Ran
A1  - Al-Mahdawi, Sahar
A1  - Pook, Mark A.
A1  - Leimkühler, Silke
A1  - Rouault, Tracey A.
A1  - Li, Kuanyu
T1  - Novel Frataxin Isoforms May Contribute to the Pathological Mechanism of
 Friedreich Ataxia
JF  - PLOS ONE
N2  - Friedreich ataxia (FRDA) is an inherited neurodegenerative disease caused by frataxin (FXN) deficiency. The nervous system and heart are the most severely affected tissues. However, highly mitochondria-dependent tissues, such as kidney and liver, are not obviously affected, although the abundance of FXN is normally high in these tissues. In this study we have revealed two novel FXN isoforms (II and III), which are specifically expressed in affected cerebellum and heart tissues, respectively, and are functional in vitro and in vivo. Increasing the abundance of the heart-specific isoform III significantly increased the mitochondrial aconitase activity, while over-expression of the cerebellum-specific isoform II protected against oxidative damage of Fe-S cluster-containing aconitase. Further, we observed that the protein level of isoform III decreased in FRDA patient heart, while the mRNA level of isoform II decreased more in FRDA patient cerebellum compared to total FXN mRNA. Our novel findings are highly relevant to understanding the mechanism of tissue-specific pathology in FRDA.
Y1  - 2012
U6  - https://doi.org/10.1371/journal.pone.0047847
SN  - 1932-6203
VL  - 7
IS  - 10
PB  - PUBLIC LIBRARY SCIENCE
CY  - SAN FRANCISCO
ER  - 
TY  - JOUR
A1  - Bindschadler, Robert A.
A1  - Nowicki, Sophie
A1  - Abe-Ouchi, Ayako
A1  - Aschwanden, Andy
A1  - Choi, Hyeungu
A1  - Fastook, Jim
A1  - Granzow, Glen
A1  - Greve, Ralf
A1  - Gutowski, Gail
A1  - Herzfeld, Ute
A1  - Jackson, Charles
A1  - Johnson, Jesse
A1  - Khroulev, Constantine
A1  - Levermann, Anders
A1  - Lipscomb, William H.
A1  - Martin, Maria A.
A1  - Morlighem, Mathieu
A1  - Parizek, Byron R.
A1  - Pollard, David
A1  - Price, Stephen F.
A1  - Ren, Diandong
A1  - Saito, Fuyuki
A1  - Sato, Tatsuru
A1  - Seddik, Hakime
A1  - Seroussi, Helene
A1  - Takahashi, Kunio
A1  - Walker, Ryan
A1  - Wang, Wei Li
T1  - Ice-sheet model sensitivities to environmental forcing and their use in projecting future sea level (the SeaRISE project)
JF  - Journal of glaciology
N2  - Ten ice-sheet models are used to study sensitivity of the Greenland and Antarctic ice sheets to prescribed changes of surface mass balance, sub-ice-shelf melting and basal sliding. Results exhibit a large range in projected contributions to sea-level change. In most cases, the ice volume above flotation lost is linearly dependent on the strength of the forcing. Combinations of forcings can be closely approximated by linearly summing the contributions from single forcing experiments, suggesting that nonlinear feedbacks are modest. Our models indicate that Greenland is more sensitive than Antarctica to likely atmospheric changes in temperature and precipitation, while Antarctica is more sensitive to increased ice-shelf basal melting. An experiment approximating the Intergovernmental Panel on Climate Change's RCP8.5 scenario produces additional first-century contributions to sea level of 22.3 and 8.1 cm from Greenland and Antarctica, respectively, with a range among models of 62 and 14 cm, respectively. By 200 years, projections increase to 53.2 and 26.7 cm, respectively, with ranges of 79 and 43 cm. Linear interpolation of the sensitivity results closely approximates these projections, revealing the relative contributions of the individual forcings on the combined volume change and suggesting that total ice-sheet response to complicated forcings over 200 years can be linearized.
Y1  - 2013
U6  - https://doi.org/10.3189/2013JoG12J125
SN  - 0022-1430
VL  - 59
IS  - 214
SP  - 195
EP  - 224
PB  - International Glaciological Society
CY  - Cambridge
ER  -